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L. Crinò
Moderator of
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OA03 - Immunotherapy Checkpoint Inhibitors in Advanced NSCLC (ID 367)
- Event: WCLC 2016
- Type: Oral Session
- Track: Chemotherapy/Targeted Therapy/Immunotherapy
- Presentations: 8
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OA03.01 - First-Line Nivolumab Monotherapy and Nivolumab plus Ipilimumab in Patients with Advanced NSCLC: Long-Term Outcomes from CheckMate 012 (Abstract under Embargo until December 5, 7:00 CET) (ID 5364)
11:00 - 11:10 | Author(s): S.N. Gettinger, N. Rizvi, L.Q. Chow, H. Borghaei, J. Brahmer, F. Shepherd, N.E. Ready, D.E. Gerber, S.J. Antonia, J.W. Goldman, R. Juergens, W.J. Geese, T.C. Young, X. Li, M.D. Hellmann
- Abstract
- Presentation
Background:
Nivolumab, a programmed death 1 (PD-1) immune checkpoint inhibitor antibody, has demonstrated improved efficacy and tolerability vs docetaxel in patients with advanced NSCLC that progressed on or after platinum-based chemotherapy and is approved in >50 countries in this patient population. We report efficacy and safety data from a phase 1 study (CheckMate 012; NCT01454102) evaluating first-line nivolumab in patients with advanced NSCLC.
Methods:
Patients (N=52) with advanced, chemotherapy-naive NSCLC (any histology) were treated with nivolumab monotherapy at 3 mg/kg IV Q2W until disease progression or unacceptable toxicity. Safety and tolerability was the primary study objective. Efficacy, as measured by objective response rate (ORR) and 24-week progression-free survival (PFS) rate per RECIST v1.1, was the secondary objective. Overall survival (OS) was an exploratory endpoint.
Results:
Treatment-related adverse events (TRAEs) were reported in 71% (any grade) and 19% (grade 3‒4) of patients. The most frequent select TRAEs (those with potential immunologic causes) by category were skin, endocrine, and gastrointestinal (Table). With a median follow-up of 14.3 months (range, 0.2 to 30.1), the confirmed ORR was 23% (12/52) and 8% (4/52) of patients had complete responses. Of the 12 responses, 8 (67%) were ongoing at the time of database lock; median duration of response was not reached. Median OS was 19.4 months (range, 0.2‒35.8+). The 24-week PFS rate was 41% (95% CI: 27‒54); 18-month OS rate was 57% (95% CI: 42‒70). Updated long-term data will be presented, including 2-year OS and will represent the longest follow-up to date for a PD-1/PD-L1 inhibitor for first-line advanced NSCLC. Updated data from patients treated with nivolumab plus ipilimumab (N = 77) will also be presented.Nivolumab monotherapy (N=52) Safety Any grade / grade 3‒4 TRAEs,[a] n (%) 37 (71) / 10 (19) Any grade / grade 3‒4 select TRAEs,[a,b] by category (≥10% of patients), n (%) Skin 13 (25) / 2 (4) Endocrine 7 (14) / 0 (0) Gastrointestinal 6 (12) / 1 (2) Any grade / grade 3‒4 TRAEs leading to discontinuation, n (%) 6 (12) / 6 (12) Efficacy Confirmed ORR,[c] n (%) [95% CI] 12 (23) [13‒37] CR 4 (8) PR 8 (15) SD 14 (27) PD 20 (38) Unable to determine[d] 6 (12) Median DOR, mo (range) NR (4.2‒25.8+) Ongoing responders, n/N (%) 8/12 (67) Median PFS, mo (range) 3.6 (<0.1+‒28.0+) 24-week PFS, % (95% CI) 41 (27‒54) Median OS, mo (range) 19.4 (0.2‒35.8+) 1-year OS, % (95% CI) 73 (59‒83) 18-month OS, % (95% CI) 57 (42‒70) Efficacy and safety analyses, except for OS, were based on a March 2015 database lock; OS analyses were based on an August 2015 database lock.[a]No grade 5 events were reported.[b]AEs with a potential immunologic cause.[c]Includes patients with initial observations of CR and PR that were subsequently confirmed by repeat scans performed no earlier than 4 weeks after the original observation.[d]Includes patients who discontinued therapy because of disease progression before first assessment or patients only with assessments suggestive of, but that did not satisfy, the required minimum duration for SD. CR = complete response; PR = partial response; SD = stable disease; PD = progressive disease; DOR = duration of response; NR = not reached.
Conclusion:
First-line nivolumab monotherapy in patients with advanced NSCLC had a similar safety profile as previously reported in second-line NSCLC and other tumors, was well tolerated, and demonstrated durable efficacy.
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OA03.02 - Atezolizumab as 1L Therapy for Advanced NSCLC in PD-L1–Selected Patients: Updated ORR, PFS and OS Data from the BIRCH Study (ID 4799)
11:10 - 11:20 | Author(s): M.C. Garassino, N. Rizvi, B. Besse, P. Jänne, D. Christoph, S. Peters, C.K. Toh, T. Kurata, E. Carcereny Costa, M. Koczywas, E. Felip, J. Chaft, J. Qiu, M. Kowanetz, S. Coleman, S. Mocci, A. Sandler, S.N. Gettinger, M.L. Johnson
- Abstract
- Presentation
Background:
Atezolizumab, a humanized anti-PDL1 mAb, inhibits the PD-L1/PD-1 pathway to restore tumor-specific T-cell immunity, resulting in durable anti-tumor effects. BIRCH (NCT02031458) is a single-arm Phase II study of atezolizumab monotherapy in PD-L1–selected advanced NSCLC patients, across multiple therapy lines. Primary analyses (median follow-up, 8.5 months) demonstrated a meaningful ORR with durable response in chemotherapy-naive 1L and 2L+ PD-L1–selected patients. Here we report updated efficacy data in 1L patients.
Methods:
1L eligibility criteria included PD-L1–selected, advanced-stage NSCLC with no CNS metastases or prior chemotherapy. PD-L1 was centrally evaluated (VENTANA SP142 IHC assay). Patients expressing PD-L1 on ≥5% of tumor cells (TC) or tumor-infiltrating immune cells (IC), ie, TC2/3 or IC2/3, were enrolled. Patients with EGFR mutation or ALK rearrangement must have had prior TKI treatment. Atezolizumab 1200mg was administered IV q3w until radiographic disease progression or unacceptable toxicity. The primary endpoint was independent review facility(IRF)-assessed ORR. Secondary endpoints included investigator(INV)-assessed ORR, DOR, PFS (RECIST v1.1) and OS.
Results:
With a median follow-up of 14.6 months, median OS was not reached in TC3 or IC3 patients and was 20.1 months in TC2/3 or IC2/3 (ITT) patients; INV-assessed ORR was 32% and 24%, respectively (Table). Furthermore, ORR was 31% for mutant EGFR (n=13) vs 20% for wild-type EGFR patients (n=104), and 27% for mutant KRAS (n=33) vs 21% for wild-type KRAS patients (n=67). No new safety signals were observed. Updated efficacy (including IRF ORR), safety and exploratory biomarker analyses will be presented.
Conclusion:
With longer follow-up, atezolizumab continued to demonstrate promising efficacy in 1L NSCLC. These results indicate that atezolizumab has durable efficacy in the 1L setting, in EGFR and KRAS mutant and wild-type tumors, and support ongoing Phase III trials evaluating atezolizumab vs chemotherapy in 1L NSCLC.
NE, not estimable.[a ]TC ≥50% or IC ≥10% PD-L1–expressing cells.[b ]TC or IC ≥5% PD-L1–expressing cells.Endpoint(95% CI) TC3 or IC3[a](n=65) TC2/3 or IC2/3[b](n=139) INV ORR, % 32% (21.2–45.1) 24% (16.9–31.7) EGFR mutant/wild-type, % 25%/29% 31%/20% KRAS mutant/wild-type, % 38%/27% 27%/21% mDOR, mo 13.1 (8.5–NE) 13.1 (9.9–17.5) mOS, mo NE (12.0–NE) 20.1 (20.1–NE) 12-mo OS rate, % 61% (48.8–73.8) 66% (57.9–74.5) mPFS, mo 7.3 (4.9–12.0) 7.3 (5.6–9.1) 12-mo PFS rate, % 36% (23.8–48.8) 32% (24.0–40.7)
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OA03.03 - JAVELIN Solid Tumor: Safety and Clinical Activity of Avelumab (Anti-PD-L1) as First-Line Treatment in Patients with Advanced NSCLC (Abstract under Embargo until December 5, 7:00 CET) (ID 3717)
11:20 - 11:30 | Author(s): G. Jerusalem, F.L. Chen, D.R. Spigel, N. Iannotti, E.F. McClay, C.H. Redfern, J. Bennouna, M. Taylor, H. Kaufman, K. Kelly, V. Chand, A. Von Heydebreck, C. Verschraegen
- Abstract
- Presentation
Background:
Avelumab* (MSB0010718C) is a fully human anti-PD-L1 IgG1 antibody that has shown antitumour activity in various malignancies. We report safety and clinical activity of avelumab as first-line therapy in a cohort of patients with non-small–cell lung cancer (NSCLC) from a phase 1b trial (NCT01772004).
Methods:
Patients with advanced NSCLC not previously treated systemically for metastatic or recurrent disease, without an activating EGFR mutation or ALK rearrangement, and not preselected for PD-L1 expression, received avelumab 10 mg/kg IV over 1 hour Q2W until progression, unacceptable toxicity, or study withdrawal. Objective response rate (ORR) and progression-free survival (PFS) were evaluated by RECIST v1.1. Adverse events (AEs) were graded by NCI-CTCAE v4.0.
Results:
As of 23 Oct 2015, 145 patients had received avelumab (median 10 weeks of treatment; range 2-30) and were followed for a median of 13 weeks (range 0-31). Median age was 70 years (range 41-90), ECOG PS was 0 (31.0%) or 1 (69.0%), and tumour histology was adenocarcinoma (63.4%) or squamous (26.9%) in most patients. Eighty-two patients (56.6%) had a treatment-related (TR) AE; those occurring in ≥10% were infusion-related reaction (IRR; n=24, 16.6%) and fatigue (n=21, 14.5%). Thirteen patients (9.0%) had a grade ≥3 TRAE; only IRR and fatigue occurred in >1 patient (each n=3, 2.1%). Four patients (2.8%) had a potential immune-mediated TRAE, all grade 1-2 (pneumonitis n=3, 2.1%; hypothyroidism n=1, 0.7%). There were no treatment-related deaths. Among 75 patients with ≥3 months’ follow-up, unconfirmed ORR was 18.7% (95% CI: 10.6, 29.3) based on 1 complete response and 13 partial responses; 12 were ongoing. Thirty-four additional patients (45.3%) had stable disease as best response (disease control rate 64.0%). Updated analysis will be presented, including efficacy data with ≥3 months’ follow-up in all patients and PD-L1 analysis.
Conclusion:
First-line avelumab monotherapy showed clinical activity and was well-tolerated in patients with EGFR-wildtype/ALK-negative NSCLC unselected for PD-L1 expression. A phase 3 trial of avelumab vs platinum-doublet in first-line NSCLC is in progress. *Proposed nonproprietary name.
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OA03.04 - Discussant for OA03.01, OA03.02, OA03.03 (ID 6946)
11:30 - 11:45 | Author(s): E.B. Garon
- Abstract
- Presentation
Abstract not provided
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OA03.05 - Analysis of Early Survival in Patients with Advanced Non-Squamous NSCLC Treated with Nivolumab vs Docetaxel in CheckMate 057 (Abstract under Embargo until December 5, 7:00 CET) (ID 4392)
11:45 - 11:55 | Author(s): S. Peters, F. Cappuzzo, L. Horn, L. Paz-Arez, H. Borghaei, F. Barlesi, M. Steins, E. Felip, D.R. Spigel, C. Dorange, H. Lu, D. Healey, T. Kong Sanchez, P. Bhagavatheeswaran, J. Novotny Jr., B. Lestini, J. Brahmer
- Abstract
- Presentation
Background:
Nivolumab significantly improved OS versus docetaxel in patients with previously treated advanced non-squamous NSCLC (CheckMate 057; NCT01673867). Kaplan−Meier OS curves for nivolumab and docetaxel crossed at ~7 months, suggesting non-proportional hazards between arms.
Methods:
Post-hoc analyses were conducted to explore relationships between baseline patient/disease characteristics, including PD-L1 expression, and death within the first 3 months of treatment (3motx). Additionally, the association between PD-L1 expression level and magnitude of clinical benefit was explored.
Results:
During the first 3motx, risk of death (rDt) was numerically higher with nivolumab versus docetaxel (59 versus 44 deaths among 292 and 290 patients, respectively). Early deaths were most commonly attributed to disease progression (no treatment-related deaths occurred). At 3motx, 80% of nivolumab-treated patients (233/292) and 85% of docetaxel-treated patients (246/290) were alive. After 3motx, the rDt was consistently higher in the docetaxel arm. In univariate analyses, no single baseline factor, including PD-L1 expression, EGFR mutation, ECOG PS, or smoking status, reliably characterized the rDt within the first 3motx with nivolumab. Among patients alive >3 months, the OS HR (95% CI) favored nivolumab in the overall population (0.59 [0.47−0.74]) and PD-L1 non-expressors (PD-L1 expression <1%; 0.66 [0.45−0.97]). In a multivariate analysis, factors associated with higher rDt within the first 3motx on nivolumab versus docetaxel were ECOG PS=1, time since last treatment <3 months, and/or progressive disease as best response to prior treatment combined with lower or no PD-L1 expression. However, the majority of nivolumab-treated patients with these attributes (including PD-L1 non-expressors), did not die within the first 3motx and experienced subsequent benefit. PD-L1 expression was a continuum, ranging from 1 to 100%, with increasing expression associated with enhanced ORR/OS benefit from nivolumab.
Conclusion:
In CheckMate 057, the benefit−risk profile of nivolumab versus docetaxel was favorable across the overall patient population. During the first 3motx, a small difference in the number of deaths (n=15) was observed; thereafter the OS rate consistently favored nivolumab (2-year OS was >2-fold higher with nivolumab versus docetaxel). Patients with poorer prognostic factors and/or more aggressive disease combined with lower or no PD-L1 expression appeared to be at higher rDt within the first 3motx on nivolumab versus docetaxel. With the exception of PD-L1 status, these are recognized prognostic factors. While PD-L1 expression may help inform individual treatment decisions, PD-L1 status alone is not considered an appropriate biomarker for nivolumab treatment selection in pre-treated advanced NSCLC, but rather should be considered in the context of other patient/disease characteristics.
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OA03.06 - Evaluation of Toxicity Profile of PD-1 versus PD-L1 Inhibitors in Non-Small Cell Lung Cancer (NSCLC) (ID 6073)
11:55 - 12:05 | Author(s): R.N. Pillai, M. Behera, T.K. Owonikoko, A.O. Kamphorst, S. Pakkala, C.P. Belani, F.R. Khuri, R. Ahmed, S.S. Ramalingam
- Abstract
- Presentation
Background:
Monoclonal antibodies against Programmed Death 1 (PD-1) and Programmed Death Ligand 1 (PD-L1) have emerged as effective therapies in NSCLC. We updated our initial systematic review of trials investigating differences in the toxicities of PD-1 and PD-L1 inhibitors.
Methods:
An electronic literature search was performed of public databases (MEDLINE, EMBASE) and conference proceedings for trials utilizing PD-1 inhibitors (nivolumab, pembrolizumab) and PD-L1 inhibitors (atezolizumab, durvalumab, avelumab) in NSCLC patients. Studies that did not report toxicities were excluded. A formal meta-analysis was conducted with Comprehensive Meta-Analysis software (Version 2.2). Clinical and demographic characteristics, response, and toxicity data were compared between the two groups.
Results:
Twenty-two studies reported between 2013-2016 were eligible for this analysis. The total number of patients evaluated for toxicities were 2,863 patients in the PD-1 group and 2,006 patients in the PD-L1 group. Patient characteristics % (PD-1/PD-L1): median age 64/65, male 58/56, smokers 82/83, squamous histology 25/32, performance status 0-1 98/100. There was no difference in response rate between PD-1 (17%) and PD-L1 (18%) inhibitors, p=0.3. The incidence of overall adverse events (AEs), immune related AEs, and pneumonitis trended in favor of the PD-L1 group but did not reach statistical significance (see table). Figure 1
Conclusion:
In this updated systematic review involving 4,869 patients, the toxicity profiles of PD-1 and PD-L1 inhibitors in NSCLC patients are not significantly different.
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OA03.07 - KEYNOTE-010: Durable Clinical Benefit in Patients with Previously Treated, PD-L1-Expressing NSCLC Who Completed Pembrolizumab (ID 6769)
12:05 - 12:15 | Author(s): R. Herbst, E.B. Garon, D. Kim, B.C. Cho, S.M. Gadgeel, H. Léna, A. Gúrpide, J. Han, C. Dubos Arvis, M. Majem, M. Forster, I. Monnet, S. Novello, H. Saka, Z. Szalai, M.A. Gubens, W. Su, G.M. Lubiniecki, Y. Shentu, G.L. Ferraro, P. Baas
- Abstract
- Presentation
Background:
Checkpoint inhibitors such as the anti–PD-1 monoclonal antibody pembrolizumab have demonstrated antitumor activity and a manageable safety profile in several advanced malignancies. Although checkpoint inhibitors are rapidly becoming a standard-of-care therapy in multiple tumor types, the optimal treatment duration has not been established. We assessed outcomes in patients who completed the maximum 24 months of pembrolizumab in the phase 3 KEYNOTE-010 study (NCT01905657), in which pembrolizumab provided superior OS over docetaxel in patients with previously treated, PD-L1–expressing advanced NSCLC.
Methods:
1034 patients with advanced NSCLC that progressed after ≥2 cycles of platinum-based chemotherapy (and an appropriate therapy for targetable EGFR and ALK aberrations if present) and had a PD-L1 tumor proportion score ≥1% were randomized 1:1:1 to pembrolizumab 2 or 10 mg/kg Q3W or to docetaxel 75 mg/m[2] until disease progression, intolerable toxicity, or physician or patient decision; the maximum duration of pembrolizumab was 24 months of uninterrupted treatment or 35 cycles, whichever was later. Response was assessed per RECIST v1.1 by independent central review every 9 weeks. After completion of 24 months/35 cycles, patients continued to undergo imaging every 9 weeks; patients with subsequent disease progression were eligible for a second treatment course if they did not receive other anticancer therapy after stopping pembrolizumab.
Results:
In the overall population, median OS was longer (10.5 months for pembrolizumab Q2W, 13.4 months for pembrolizumab Q3W, and 8.6 months for docetaxel) and 24-month OS rates were higher (30.1%, 37.5%, and 14.5%, respectively) with pembrolizumab compared with docetaxel. Of the 691 patients allocated to pembrolizumab, 47 patients received 35 cycles of pembrolizumab and were included in this analysis. As of the September 30, 2016 data cutoff date, all patients had completed all 35 cycles of treatment, but one withdrew from the study treatment after completing 35 cycles. Best overall response (ORR) among these 47 patients was complete response (CR) in 3 (6%) patients and partial response (PR) in 39 (83%) patients, for an ORR of 89%; 5 (11%) patients experienced stable disease (SD). Two of these patients experienced disease progression since stopping pembrolizumab and two of these patients resumed pembrolizumab therapy. As of the cutoff date, none of the 47 patients had died.
Conclusion:
With long-term follow-up, the OS benefit has been maintained and pembrolizumab continues to demonstrate superiority over docetaxel. Pembrolizumab provides durable clinical benefit with few patients progressing after completing two years of therapy.
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OA03.08 - Discussant for OA03.05, OA03.06, OA03.07 (ID 7009)
12:15 - 12:30 | Author(s): P. Mitchell
- Abstract
- Presentation
Abstract not provided
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Author of
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MA04 - HER2, P53, KRAS and Other Targets in Advanced NSCLC (ID 380)
- Event: WCLC 2016
- Type: Mini Oral Session
- Track: Advanced NSCLC
- Presentations: 1
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MA04.06 - Signaling Networks in KRAS-Mutant Advanced NSCLC: A Complex Landscape Involving Immunoresponse, Inflammation and DNA Repair (ID 5768)
16:36 - 16:42 | Author(s): L. Crinò
- Abstract
- Presentation
Background:
KRAS is the most frequently mutated oncogene in Non-Small Cell Lung Cancer (NSCLC) and its role as prognostic and predictive biomarker remains widely debated. Unfortunately, KRAS direct targeting strategies have been unsuccessful and no approved target therapy exists for KRAS-mutant-NSCLC. This pilot study evaluated the activated signaling architecture of advanced NSCLC harbouring a KRAS mutation to better characterize the signaling network driving this subgroup of pulmonary malignancies.
Methods:
Twenty Stage IV Formalin-fixed, paraffin-embedded (FFPE) NSCLCs were collected from chemo-naïve patients at S. Maria della Misericordia Hospital (Perugia, Italy). Ten tumors were KRAS-wild-type (KRAS-WT) and ten were KRAS-Mutant (KRAS-MUT). Whole-tissue lysates were obtained for all samples. Signaling network analysis was performed using the Reverse Phase Protein Array (RPPA) platform to quantitatively evaluate the expression/activation of 148 key proteins and phosphoproteins involved in cellular growth, survival, proliferation, apoptosis, autophagy, inflammation, invasion and cell motility. Wilcoxon Rank-Sum Test was used to compare the signaling architecture of KRAS-MUT and KRAS-WT tumours. All p-values <0.05 were considered significant. Non-parametric correlation analysis was performed to explore the signaling interconnection within each group of patients. Only correlations with p<0.0001 were considered significant.
Results:
This preliminary analysis revealed a statistically significant different activation level of 20 proteins between the KRAS-MUT and KRAS-WT samples. Five of the proteins that were statistically different in the KRAS-MUT group are involved in the inflammatory immunoresponse (ASK1 S83 p<0.01, Axl Y702 p=0.01, Stat2 Y690 p<0.01, Tyk2 Y1054/Y1055 p=0.01 and Twist p<0.01) and six in cell cycle control and DNA repair (ATM S1981 p=0.01; Bcl-xL p=0.03; Cleaved Caspase 3 D175 p=0.02; Histone H3 S10 p<0.01; p53 S15 p<0.01; p27 T187 p=0.04). The analytes that were statistically significant were all lower in the KRAS-MUT group compared to the WT (except for p27 T187 which decreased in the KRAS-MUT group compared to KRAS-WT). Pair-wise correlation analysis of the signaling proteins showed an overall more complex protein-protein interaction network and pathway activation (included AKT/mTOR signaling pathway) in the KRAS-MUT population with high number of statistically significant correlations compared to the KRAS-WT group.
Conclusion:
This pilot study indicated that the effect of KRAS mutation status on protein signaling in NSCLC was an alteration of the immunoresponse axis and DNA repair network. If validated in a larger cohort of patients, these results could have important clinical implications for stratification KRAS-MUT advanced NSCLC patients towards more efficacious targeted treatment and to identify new therapeutic targets based on multi-targets/multi-pathways KRAS inhibitory approach. (AIRC-supported study).
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MA07 - ALK-ROS1 in Advanced NSCLC (ID 385)
- Event: WCLC 2016
- Type: Mini Oral Session
- Track: Advanced NSCLC
- Presentations: 2
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MA07.01 - Updated Pooled Analysis of CNS Endpoints in Two Phase II Studies of Alectinib in ALK+ NSCLC (ID 5354)
11:00 - 11:06 | Author(s): L. Crinò
- Abstract
- Presentation
Background:
Based on two single-arm, multicentre, phase II studies (NP28673 [NCT01801111] and NP28761 [NCT01871805]), the FDA approved the ALK inhibitor alectinib for use in ALK+ NSCLC patients after prior crizotinib. Alectinib was well tolerated in both phase II studies and showed efficacy against both systemic and central nervous system (CNS) disease, the latter being a common progression site in ALK+ NSCLC. This analysis uses pooled data from the latest cut-offs (22 Jan 2016 for NP28761; 1 Feb 2016 for NP28673) to examine the long-term CNS efficacy of alectinib.
Methods:
Both studies enrolled crizotinib-refractory patients ≥18 years with ECOG PS 0–2 and locally advanced or metastatic ALK+ NSCLC (confirmed by FDA-approved test). CNS metastases were permitted if asymptomatic. Patients received 600mg oral alectinib BID. The primary endpoint in both studies was objective response rate (ORR) by independent review committee; secondary CNS endpoints included CNS ORR, CNS duration of response (DoR), and CNS disease control rate (DCR). CNS response and progression were determined by RECIST v1.1. All patients had baseline imaging to assess CNS metastases, with further imaging every 6 or 8 weeks for NP28761 and NP28673, respectively.
Results:
The overall pooled analysis population comprised 225 patients (n=87 from NP28761; n=138 from NP28673); median follow-up for this updated analysis was 18.8 (0.6–29.7) months (>6 months additional follow-up). At baseline, 50 patients had measurable and 86 had non-measurable CNS disease; together, these groups comprised 136 patients, 60% of the overall pooled population. Seventy percent of patients had prior CNS radiotherapy; 58% of these completed radiotherapy >6 months before study entry. Updated CNS data are shown in the Table and are consistent with systemic results.Measurable CNS disease at baseline (n=50) Measurable and non-measurable CNS disease at baseline (n=136) CNS ORR, n (%) [95% CI] 32 (64.0) [49.2–77.1] 60* (44.1) [35.6–52.9] Complete response (CR), n (%) 11 (22.0) 39* (28.7) CNS DCR, n (%) [95% CI] 45 (90.0) [78.2–96.7] 117 (86.0) [79.1–91.4] Median CNS DoR, months [95% CI] Patients with event, n (%) 11.1 [7.6–NE] 18 (56.3) 13.8 [11.0–21.5] 32 (53.3) * N.B. Non-measurable disease response can only be classified as CR, non-CR/non-progressive disease (PD) or PD
Conclusion:
This updated pooled analysis with mature data confirms that alectinib can provide long-term control of CNS metastases in ALK+ NSCLC, with a high CR rate.
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MA07.06 - Crizotinib in ROS1 Rearranged or MET Deregulated Non-Small-Cell Lung Cancer (NSCLC): Preliminary Results of the METROS Trial (ID 6003)
11:36 - 11:42 | Author(s): L. Crinò
- Abstract
- Presentation
Background:
Crizotinib is an orally active inhibitor of receptor tyrosine kinases effective in NSCLC with ALK rearrangement. Recent data showed that this agent is dramatically effective in patients with ROS1 rearrangement and at least in some patients with MET deregulation, particularly individuals with exon 14 skipping mutations or with high levels of MET amplification.
Methods:
The METROS trial is a multicenter prospective phase II study designed to assess the efficacy and safety and tolerability of Crizotinib in pretreated metastatic NSCLC with MET amplification or MET exon 14 mutation or ROS1 rearrangement. The co-primary end-point was response rate to crizotinib in two cohorts of patients: cohort A) ROS1+: patients with ROS1 rearrangement; B) MET+: patients with MET amplification defined as ratio MET/CEP7 >2.2 on FISH testing or MET exon 14 skipping mutations. Eligible patients were treated with with crizotinib at the standard dose of 250 mg BID p.o.
Results:
At the time of the present analysis, preliminary data on the MET cohort are available. A total of 249 patients were screened and 18 resulted as MET+ (12 amplified and 6 mutated). Among them, 10 patients (9 amplified and 1 mutated) were included onto the study and received at least one dose of crizotinib, 6 patients were not eligibible beacause of not progressing to front line therapy, whereas 2 patients did not received crizotinib due to rapidly progressive disease. Characteristics of enrolled patients were: median age 68 years (range 39-77); male/female 8/2; ECOG PS 0/1/2: 6/3/1. In 8 cases crizotinib was offered as second-line therapy. All but one patients were current or past smokers. According to RECIST criteria, 2 partial responses and 4 stable disease were so far documented, with an overall disease control rate of 60%. Three patients are still on treatment. Therapy was generally well tolerated, with only 1 patient delaying therapy due to adverse events. Enrollment is still ongoing.
Conclusion:
Preliminary analysis of the METROS trial supports the potential efficacy of crizotinib in patients with MET deregulation, with a favorable toxicity profile. Updated results including median progression-free survival and survival were will be presented at the meeting.
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MA14 - Immunotherapy in Advanced NSCLC: Biomarkers and Costs (ID 394)
- Event: WCLC 2016
- Type: Mini Oral Session
- Track: Advanced NSCLC
- Presentations: 1
- Moderators:M. Reck, D.R. Spigel
- Coordinates: 12/06/2016, 16:00 - 17:30, Strauss 2
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MA14.06 - Nivolumab in Never Smoker Patients with Advanced Squamous NSCLC: Results from the Italian Expanded Access Programme (EAP) (ID 4765)
16:36 - 16:42 | Author(s): L. Crinò
- Abstract
- Presentation
Background:
Nivolumab is the first checkpoint inhibitor approved for the treatment of Sq-NSCLC to show a survival benefit vs the standard of care docetaxel in the randomised, phase III, CheckMate 017 study. In the nivolumab development program, a greater clinical benefit was shown in current and former smokers than in never smokers. Nevertheless, no data are available in this respect from a real world setting. For this reason, we decided to use the data collected in the EAP in order to assess the effectiveness and tolerability of nivolumab treatment in the never smoker patient population.
Methods:
Nivolumab was provided upon physician request for patients aged ≥18 years who had relapsed after a minimum of one prior systemic treatment for stage IIIB/stage IV Sq-NSCLC. Nivolumab 3 mg/kg was administered intravenously every 2 weeks for <24 months. Patients included in the analysis had received ≥1 dose of nivolumab and were monitored for adverse events using Common Terminology Criteria for Adverse Events.
Results:
Of 372 patients with Sq-NSCLC participating in the EAP in Italy, 38 (10.2%) were never smokers, a proportion very similar to the one observed in Checkmate 017 (10%). With a median number of doses of 8 (range, 1–22) and a median follow-up of 5.6 months, the disease control rate in this group was 50%, including 9 patients with a partial response and 10 with stable disease. Eight patients were treated beyond RECIST-defined progression, with 4 of them achieving disease control. As of April 2016, median progression-free survival and overall survival were 3.5 months and not reached, respectively. 17 patients (44.7%) discontinued treatment for any reason except toxicity and 5 (13.1%) discontinued due to AE.
Conclusion:
These preliminary results, although obtained from a small sample size, suggest that nivolumab is effective and well tolerated in a never smoker group of patients with advanced Sq-NCLCS in the real life and warrant further investigation in this area.
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MA16 - Novel Strategies in Targeted Therapy (ID 407)
- Event: WCLC 2016
- Type: Mini Oral Session
- Track: Chemotherapy/Targeted Therapy/Immunotherapy
- Presentations: 1
- Moderators:G. Purkalne, J. Von Pawel
- Coordinates: 12/07/2016, 14:20 - 15:50, Strauss 2
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MA16.11 - CNS Response to Osimertinib in Patients with T790M-Positive Advanced NSCLC: Pooled Data from Two Phase II Trials (ID 4920)
15:26 - 15:32 | Author(s): L. Crinò
- Abstract
- Presentation
Background:
Brain metastases develop in 25–40% of patients with NSCLC. Osimertinib is an oral, potent, irreversible EGFR-TKI, selective for both sensitising (EGFRm) and T790M resistance mutations. Preclinical and early clinical evidence support central nervous system (CNS) penetration and activity of osimertinib. Two Phase II studies (AURA extension [NCT01802632] and AURA2 [NCT02094261]) evaluating the efficacy and safety of osimertinib are ongoing. We present a pre planned subgroup analysis assessing pooled CNS response from these two studies; data cut-off (DCO) was 1 November 2015. An earlier pooled analysis from these two studies (1 May 2015 DCO) showed the objective response rate (ORR) in patients with CNS metastases was consistent with ORR in the overall patient population.
Methods:
Patients with advanced NSCLC who progressed following prior EGFR-TKI therapy with centrally-confirmed T790M positive status (cobas® EGFR Mutation Test) received osimertinib 80 mg once daily (n=411). Patients with stable, asymptomatic CNS metastases were eligible for enrolment. CNS efficacy was assessed in an evaluable for CNS response analysis set, which included patients with at least one measurable CNS lesion on baseline brain scan (RECIST v1.1) by blinded independent central neuroradiology review (BICR). Effect of prior radiotherapy on CNS response was assessed.
Results:
As of 1 November 2015, 50/192 patients with baseline brain scans had at least one measurable CNS lesion identified by BICR. Baseline demographics were broadly consistent with the overall patient population. Confirmed CNS ORR was 54% (27/50; 95% CI: 39%, 68%), with 12% complete CNS response (6/50 patients). The median CNS duration of response (22% maturity) was not reached (95% CI: not calculable [NC], NC). The estimated percentage of patients remaining in response at 9 months was 75% (95% CI: 53, 88). CNS disease control rate (DCR) was 92% (46/50; 95% CI: 81%, 98%). Median time to first response was 5.7 weeks (range: 5.6–6.6). Median best percentage change from baseline in CNS target lesion size was 53% (range: -100% – +80%). Median follow up for CNS progression-free survival (PFS) was 11 months; the median CNS PFS was not reached (95% CI: 7, NC). At 12 months, 56% (95% CI: 40%, 70%) of patients were estimated to remain on study, alive and CNS progression-free. CNS response was observed regardless of prior radiotherapy to the brain.
Conclusion:
Osimertinib demonstrates durable efficacy in patients with T790M NSCLC and measurable CNS metastases, with a CNS response rate of 54% and a DCR of 92%.
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OA22 - Novel Trials and Biomarkers in Malignant Pleural Mesothelioma (ID 403)
- Event: WCLC 2016
- Type: Oral Session
- Track: Mesothelioma/Thymic Malignancies/Esophageal Cancer/Other Thoracic Malignancies
- Presentations: 1
- Moderators:H. Pass, N. Van Zandwijk
- Coordinates: 12/07/2016, 14:20 - 15:50, Strauss 3
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OA22.01 - STELLAR - Interim Results of a Phase 2 Trial of TTFields with Chemotherapy for First Line Treatment of Malignant Mesothelioma (ID 6034)
14:20 - 14:30 | Author(s): L. Crinò
- Abstract
- Presentation
Background:
Tumor Treating Fields (TTFields) are an anti-mitotic, regional treatment modality, based on low intensity alternating electric fields delivered non-invasively using a portable, home use, medical device. In-vitro, human mesothelioma cells were found to be highly susceptible to TTFields. TTFields have been shown to extend survival of patients with glioblastoma when added to standard of care chemotherapy.
Methods:
The trial will accrue a total of 80 patients with unresectable, previously untreated mesothelioma. Patients are treated with TTFields in combination with pemetrexed and cisplatin or carboplatin. Continuous TTFields at 150 kHz for a minimum of 18 hours/day are applied to the thorax together with standard dosing of chemotherapy. Inclusion criteria include ECOG 0-1, pathological evidence mesothelioma and at least one measurable lesion according to modified RECIST criteria. Patients are followed q3 weeks (CT scan q6 weeks) until disease progression. The primary endpoint is overall survival (OS) and secondary endpoints are response rate, progression free survival (PFS) and treatment-emergent toxicity. This prospective, single arm study assumes that historical control has an exponential survival distribution and a median survival of 12.1 Months (Vogelzang et al.). The sample size provides 80% power with a two sided alpha of 0.05 to detect a Hazard Ratio of 0.67 for OS, compared to the historical data.
Results:
To date, 42 patients have been enrolled in the trial with an average follow up time of 11.5 months. Median age is 67±9 (range 43-78), 79% are male and 48% smokers. 14% (6 patients) have metastatic disease and 33% (14 patients) have an ECOG score of 1. Median survival has not been reached at this time. The 12-month survival rate is 79.7% (95% CI 57.2-91.2) and median PFS is 7.3 months (95% CI 5.6-NA). No device-related serious adverse events (AEs) have been reported to date. Expected TTFields-related dermatitis was reported in 55% (23 patients). Only 2 patients had grade 3 dermatitis. The following severe (grade 3-4) systemic AEs were reported: hematological (26%), hepatobiliary (2%), respiratory (2%).
Conclusion:
These interim results of the ongoing STELLAR study demonstrated no safety concerns for the combination of TTFields to the thorax together with standard chemotherapy for previously untreated mesothelioma patients. The 12-month survival rate was significantly higher, and PFS longer, than that of historical controls reported by Vogelzang et al. Final analysis of the study will be performed after enrollment and follow up of all 80 patients in the study are completed.
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P1.02 - Poster Session with Presenters Present (ID 454)
- Event: WCLC 2016
- Type: Poster Presenters Present
- Track: Biology/Pathology
- Presentations: 1
- Moderators:
- Coordinates: 12/05/2016, 14:30 - 15:45, Hall B (Poster Area)
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P1.02-005 - Frequency of Actionable Alterations in EGFR wt NSCLC: Experience of the Wide Catchment Area of Romagna (AVR) (ID 3934)
14:30 - 14:30 | Author(s): L. Crinò
- Abstract
Background:
Epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors have improved the outcome of patients with EGFR-mutated lung adenocarcinoma (ADC). However, EGFR mutation occurred in about only 10-15% of ADC, but other alterations are emerging as potential target of drugs. We analyzed the frequency of potentially targetable driver alterations in a series of advanced EGFR-wild type (wt) NSCLC patients.
Methods:
724 advanced EGFR-wt NSCLC patients enrolled from the Wide Catchment Area of Romagna (AVR) between January 2013 to December 2014 were included in the study. KRAS, BRAF, ERBB2, PIK3CA, NRAS, ALK, MAP2K1, RET and DDR2 mutations were analyzed by Myriapod[®]Lung Status kit (Diatech Pharmacogenetics) on MassARRAY[®] (SEQUENOM[®] Inc, California). ERBB4 was evaluated by direct sequencing and EML4-ALK and ROS1 rearrangements were assessed by immunohistochemistry or fluorescence in situ hybridization.
Results:
331 (45.7%) patients showed at least one alteration. Of these, 72.2%, 6.3%, 3.6%, 1.8%, 2.1% and 1.2% patients had mutations in KRAS, BRAF, PIK3CA, NRAS, ERBB2 and MAP2K1 genes, respectively. Only one patient showed a mutation in ERBB4 gene. EML4-ALK and ROS1 rearrangements were observed in 4.3% and 1.4% of all patients, respectively. The distribution of mutations in relation to gender and smoking habits is reported in the Table. Overlapping mutations were observed in 7 KRAS-mutated patients: 2 (28.6%) patients were also mutated in PIK3CA, 4 (57.1%) showed also an EML4- ALK translocation and one (14.3%) had a ROS1 rearrangement. One (0.3%) patient showed both BRAF and PIK3CA alterations. Correlation analyses between the different mutations and patient outcome are ongoing.
*: some data are missingGENE Mutated Patients N (%) Gender Smoking Habits* Female (%) Male (%) Smoker (%) Never Smoker (%) KRAS 239 (33) 93 (39) 146 (61) 115 (48.1) 9 (3.8) BRAF 21 (3) 11 (52.4) 10 (47.6) 11 (52.4) 1 (4.8) NRAS 6 (0.8) 4 (66.7) 2 (33.3) 4 (66.7) - PIK3CA 12 (1.6) 4 (33.3) 8 (66.7) 5 (41.7) - MAP2K1 4 (0.5) - 4 (100) 1 (25) - ERBB2 7 (0.9) 5 (71.4) 2 (28.6) - 1 (14.3) EML4-ALK 31 (4.3) 20 (64.5) 11 (35.5) 12 (38.7) 8 (25.8) ROS1 10 (1.4) 7 (70) 3 (30) 3 (30) 5 (50)
Conclusion:
Driver mutations were detected in about 50% of EGFR wt lung ADC patients. Such alterations could represent potential targets for therapy and could be evaluated in routine multiplexed testing to obtain a wider tumor molecular characterization.
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P1.06 - Poster Session with Presenters Present (ID 458)
- Event: WCLC 2016
- Type: Poster Presenters Present
- Track: Advanced NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 12/05/2016, 14:30 - 15:45, Hall B (Poster Area)
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P1.06-006 - Treatment beyond Progression in Patients with Advanced Squamous NSCLC Participating in the Expanded Access Programme (EAP) (ID 5450)
14:30 - 14:30 | Author(s): L. Crinò
- Abstract
Background:
Response patterns of immunotherapies differ from those seen with other therapies approved for the treatment of tumors. Due to this reason, immunotherapy protocols generally allow patients (pts) to continue treatment beyond investigator-assessed radiographic progressive disease (PD) as long as there is ongoing clinical benefit, but to date no data has been reported regarding treatment beyond PD in routine clinical practice. Here we report the analysis about the subgroup of pts treated beyond initial PD in the italian cohort of nivolumab EAP for pts with squamous non small cell lung cancer (Sq-NSCLC).
Methods:
Nivolumab was available upon physician request for pts aged ≥18 years who had relapsed after a minimum of one prior systemic treatment for stage IIIB/stage IV Sq-NSCLC. Nivolumab 3 mg/kg was administered intravenously every 2 weeks to a maximum of 24 months. Pts included in the analysis had received ≥ 1 dose of nivolumab and were monitored for adverse events (AE) using Common Terminology Criteria for Adverse Events. Patients were allowed to continue treatment beyond initial PD as long as they met the following criteria: investigator-assessed clinical benefit, absence of rapid PD, tolerance of program drug, stable performance status and no delay of an imminent intervention to prevent serious complications of PD.
Results:
With a median follow-up of 5.2 months (range 0-12.9), 363 pts were evaluable for response. Prior to first progression, the objective response rate (ORR) was 14%, with 1 complete response (CR) and 50 (14%) partial responses (PR), and the disease control rate (DCR) was 41%. Sixty-six pts were treated beyond RECIST defined progression, with 23 pts obtaining a non-conventional benefit, meaning a subsequent tumor reduction or stabilization in tumor lesions. In particular, 17 pts obtained a SD and 6 pts obtained a PR. As to July 2016, median overall survival in these pts had not been reached (95% CI: 3.2-4.6) and 6 months and 12 months OS were 75% and 53%, respectively. The safety profile was consistent to what already observed in the general population.
Conclusion:
As already observed in clinical trials, these preliminary EAP data seem to confirm that a proportion of pts who continued treatment beyond PD demonstrated sustained reduction or stabilization of tumor burden, with an acceptable safety profile. Further investigations are warranted in order to better define and identify pts who can benefit from treatment beyond progression.
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P1.07 - Poster Session with Presenters Present (ID 459)
- Event: WCLC 2016
- Type: Poster Presenters Present
- Track: SCLC/Neuroendocrine Tumors
- Presentations: 1
- Moderators:
- Coordinates: 12/05/2016, 14:30 - 15:45, Hall B (Poster Area)
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P1.07-018 - Incidence of Brain Recurrence and Survival Outcomes in High-Grade Neuroendocrine Carcinomas of the Lung: Implications for Clinical Practice (ID 3879)
14:30 - 14:30 | Author(s): L. Crinò
- Abstract
Background:
Among patients with advanced high-grade neuroendocrine carcinoma (HGNEC) of the lung, the optimal therapeutic management is much less established for large cell neuroendocrine carcinomas (LCNECs) than for small cell lung cancers (SCLCs). We evaluated the survival outcomes and incidence of brain recurrence of advanced LCNECs, and compared them with those of a population of SCLCs matched by stage.
Methods:
Forty-eight unresected stage III HGNECs (16 LCNECs and 32 SCLCs) and 113 stage IV HGNECs (37 LCNECs and 76 SCLCs) were eligible for the analysis. The efficacy of platinum-etoposide chemotherapy with or without thoracic radiotherapy (TRT) and/or prophylactic cranial irradiation (PCI) was investigated.
Results:
Overall response was significantly lower for LCNECs compared with SCLCs for both stage III (43.8% vs 90.6% respectively, P=0.004) and stage IV (43.3% vs 64.5%, respectively, P=0.04). Similarly, an inferior outcome was observed in terms of progression-free survival (PFS), and overall survival (OS) for LCNECs compared with SCLCs, which, however, reached significance only for stage III disease (median: 5.6 vs 8.9 months, P=0.06 and 10.4 vs 17.6 months, P=0.03 for PFS and OS, respectively), (Figure 1). Histologic subtype (LCNEC vs SCLC) was an independent prognosticator in multivariate analysis. In the lack of PCI, LCNECs showed a high cumulative incidence of brain metastases, as 58% and 48% of still living stage III and IV patients, respectively, developed brain metastases at 18 moFigure 1
Conclusion:
Patients with advanced LCNECs are at high risk for brain recurrence. Unresected stage III LCNECs treated with platinum-etoposide with or without TRT bear a dismal prognosis, when compared indirectly with SCLC counterparts. Randomized trials should evaluate whether PCI could improve survival of advanced LCNECs.
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P2.03b - Poster Session with Presenters Present (ID 465)
- Event: WCLC 2016
- Type: Poster Presenters Present
- Track: Advanced NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 12/06/2016, 14:30 - 15:45, Hall B (Poster Area)
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P2.03b-031 - Impact of PD-L1 Status on Clinical Response in SELECT-1: Selumetinib + Docetaxel in KRASm Advanced NSCLC (ID 5040)
14:30 - 14:30 | Author(s): L. Crinò
- Abstract
Background:
Anti-PD-1/PD-L1 immunotherapy has delivered clinical benefit for patients with NSCLC, and PD-L1 has emerged as a predictive biomarker. In the Phase III SELECT-1 trial (NCT01933932), selumetinib (AZD6244, ARRY-142886), an oral, potent and selective, allosteric MEK1/2 inhibitor with a short half-life, plus second-line docetaxel did not provide clinical benefit for patients with KRAS-mutant (KRASm) NSCLC compared with placebo plus docetaxel (PBO+DOC). Although no incremental benefit was observed, it is important to evaluate biomarkers, such as PD-L1, to understand more about the biology of patients with KRASm NSCLC.
Methods:
In total, 510 patients with a prospectively, centrally confirmed KRAS mutation (cobas® KRAS Mutation Test, Roche Molecular Systems) were randomised 1:1 to selumetinib 75 mg BID, plus docetaxel 75 mg/m[2] q21d (SEL+DOC), or PBO+DOC. Evaluations included progression-free survival (PFS) by investigator assessment (RECIST 1.1; primary endpoint), and overall survival (OS). Association of tumour PD-L1 status with clinical responses was assessed as an exploratory objective. PD-L1 status was centrally determined using the PD-L1 IHC 28-8 pharmDx test (Dako) for all patients with sufficient tumour sample. Samples with a pre-specified cut-off of ≥5% tumour cell staining were considered PD-L1 positive.
Results:
SEL+DOC did not improve PFS or OS compared with PBO+DOC. PD-L1 status was determined for 385 (75%) patients: 224 (58%) samples were PD-L1 <5%, and 161 (42%) samples were PD-L1 ≥5%; the remaining 125 patients had unknown PD-L1 status due to insufficient tumour sample. Subgroups were balanced across treatments. PD-L1 subgroup analysis of PFS and OS is presented below.Subgroup Events (%) in SEL+DOC group Events (%) in PBO+DOC group HR (95% CI) PFS PD-L1 <5% 94/112 (84%) 101/112 (90%) 0.89 (0.67, 1.18) PD-L1 ≥5% 65/79 (82%) 71/82 (87%) 0.70 (0.50, 0.99) PD-L1 unknown 59/63 (94%) 57/62 (92%) 1.24 (0.86, 1.79) OS PD-L1 <5% 73/112 (65%) 74/112 (66%) 0.94 (0.68, 1.30) PD-L1 ≥5% 55/79 (70%) 58/82 (71%) 0.89 (0.61, 1.28) PD-L1 unknown 48/63 (76%) 38/62 (61%) 1.57 (1.02, 2.41)
Conclusion:
Prevalence of PD-L1 positive status in this KRASm cohort was similar to that reported for a pan-NSCLC cohort (Borghaei, NEJM 2015). No significant PFS or OS differences were observed between treatments in either PD-L1 positive or negative tumours. Additional biomarker analyses are planned for different KRAS codon mutations, and LKB1 and TP53 status.
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P3.02a - Poster Session with Presenters Present (ID 470)
- Event: WCLC 2016
- Type: Poster Presenters Present
- Track: Advanced NSCLC
- Presentations: 2
- Moderators:
- Coordinates: 12/07/2016, 14:30 - 15:45, Hall B (Poster Area)
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P3.02a-016 - Pooled Efficacy and Safety Data from Two Phase II Studies (NP28673 and NP28761) of Alectinib in ALK+ Non-Small-Cell Lung Cancer (NSCLC) (ID 5044)
14:30 - 14:30 | Author(s): L. Crinò
- Abstract
Background:
Alectinib is an FDA-approved ALK TKI, for treatment of patients with ALK+ metastatic NSCLC who have progressed on, or are intolerant to, crizotinib. Systemic and CNS efficacy was demonstrated in two single-arm, phase II studies (NP28673 [NCT01801111] and NP28761 [NCT01871805]). We report the pooled systemic efficacy and safety analysis of alectinib from 2016 cut-offs 22 January, NP28761 and 1 February, NP28673.
Methods:
Patients were ≥18 years, had locally advanced or metastatic ALK+ NSCLC [FDA-approved FISH test] and had progressed on, or were intolerant to, crizotinib. Patients received oral alectinib 600mg twice daily until disease progression, death or withdrawal. The pooled analysis assessed objective response rate (ORR) by an independent review committee (IRC) using RECIST v1.1 (primary endpoint in both studies); disease control rate (DCR); duration of response (DOR); progression-free survival (PFS); overall survival (OS); and safety.
Results:
The pooled dataset included 225 patients, (n=138 NP28673; n=87 NP28761). Median age was 53 years, 60% of patients had baseline CNS metastases and 77% had received prior chemotherapy. The response-evaluable (RE) population by IRC included 189 patients (84%). Median follow-up was 18.8 months (0.6–29.7). In the RE population (n=189) ORR by IRC was 51.3% (95% CI 44.0–58.6; all partial responses), a DCR of 78.8% (95% CI 72.3–84.4), with a median DOR of 14.9 months (95% CI 11.1–20.4) after 58% of events. In patients with prior chemotherapy (n=148), IRC ORR was 49.3% (95% CI 41.0–57.7); DCR: 79.1% (95% CI 71.6–85.3); median DOR: 14.9 months (95% CI 11.0–21.9) after 59% of events. In patients who were chemotherapy-naïve (n=41), IRC ORR was 58.5% (95% CI 42.1–73.7); DCR: 78.0% (95% CI 62.4–89.4); median DOR: 11.2 months (95% CI 8.0–NE) after 54% of events. In the total pooled population (n=225) median PFS by IRC was 8.3 months (95% CI 7.0–11.3) after 69% of events and median OS was 26.0 months (95% CI 21.4–NE) after 43% of events. Grade ≥3 adverse events (AEs) occurred in 40% of patients and the most common were dyspnoea (4%), elevated levels of blood creatine phosphokinase (4%) and alanine aminotransferase (3%). The mean dose intensity was 94.6%. Fourteen patients withdrew due to AEs; 20.9% had AEs leading to dose interruptions/modification.
Conclusion:
This pooled analysis confirmed alectinib has robust systemic efficacy with a durable response in this population and in patients with or without prior chemotherapy. Alectinib had an acceptable safety profile.
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P3.02a-025 - PROs With Ceritinib Versus Chemotherapy in Patients With Previously Untreated ALK-rearranged Nonsquamous NSCLC (ASCEND-4) (ID 5128)
14:30 - 14:30 | Author(s): L. Crinò
- Abstract
Background:
Here, we present the patient-reported outcomes (PROs) of ceritinib versus chemotherapy as first-line treatment for advanced ALK+ NSCLC.
Methods:
Untreated, ALK+, advanced, nonsquamous NSCLC patients (N=376) were randomized (1:1) to ceritinib 750 mg/day (n=189) or chemotherapy (n=187; [pemetrexed 500 mg/m[2 ]plus cisplatin 75 mg/m[2] or carboplatin AUC 5-6] for 4 cycles followed by maintenance pemetrexed). PROs were assessed using EORTC quality-of-life questionnaire (QLQ-C30), the lung cancer module (QLQ-LC13), Lung Cancer Symptom Scale (LCSS), and EQ-5D.
Results:
Median treatment exposure was 66.4 weeks for ceritinib and 26.9 weeks for chemotherapy. PRO compliance was high, ≥80% at most timepoints. Ceritinib significantly prolonged time to deterioration of lung cancer-specific symptoms (pain, dyspnea, and cough) versus chemotherapy in both LCSS and QLQ-LC13 instruments (composite endpoints for LCSS, HR=0.61 [0.41, 0.90]; and QLQ-LC13, HR=0.48 [0.34, 0.69]). Time to deterioration in LC13 questionnaire was significantly longer with ceritinib versus chemotherapy (23.6 [20.7, NE] vs 12.6 [8.9, 14.9] months) (Table). In the QLQ-C30 instrument, 4 of 5 functional domains and 6 of 9 symptom scales improved with ceritinib (P< 0.05); 2 scales related to gastrointestinal symptoms indicated deterioration for ceritinib. In agreement with most other scales showing symptom improvement, ceritinib demonstrated significant improvements in Global Health Status/QoL in the same instrument (QLQ-C30, P<0.001) as well as for EQ-5D-5L index (P<0.001) and EQ-5D-5L VAS (P<0.05 from cycle 13 until 49). Figure 1
Conclusion:
Untreated ALK+ NSCLC patients experienced significantly greater improvements in lung cancer-specific symptoms on treatment with ceritinib. General health status was significantly improved with ceritinib versus chemotherapy. Overall, PRO results from all 4 instruments independently showed improvements highlighting the consistency and robustness of these findings.
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P3.02b - Poster Session with Presenters Present (ID 494)
- Event: WCLC 2016
- Type: Poster Presenters Present
- Track: Advanced NSCLC
- Presentations: 3
- Moderators:
- Coordinates: 12/07/2016, 14:30 - 15:45, Hall B (Poster Area)
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P3.02b-006 - Role of TP53 Mutations in Determining Primary Resistance to First-Line Tyrosine Kinase Inhibitors in EGFR-Mutated NSCLC Patients (ID 3861)
14:30 - 14:30 | Author(s): L. Crinò
- Abstract
Background:
Patients with non-small-cell lung cancer (NSCLC) carrying specific mutations at epidermal growth factor receptor (EGFR) gene are usually sensitive to treatments with tyrosine kinase inhibitors (TKIs). However, not all EGFR-mutated patients respond equally to TKI treatments, and approximately 20-30% show primary resistance. Although the mechanisms responsible for acquired resistance are known, those responsible for primary resistance are not completely understood. In this study we aimed to assess the role of TP53 mutations in a cohort of advanced EGFR-mutated NSCLC patients receiving first-line TKIs. We analyzed TP53 gene status in relation to outcome in terms of overall response rate, disease control rate (DCR), response duration, progression free survival (PFS) and overall survival (OS).
Methods:
We retrospectively analyzed 136 patients with advanced EGFR-mutated NSCLC treated with first-line TKIs from January 2012 to April 2015. Exons 5-8 of TP53 gene were amplified by PCR and sequenced by direct sequencing on 123 patients. DCR was defined as the sum of complete response, partial response and stable disease. The survival endpoints examined were PFS and OS. PFS was defined as the time from start of first-line treatment to disease progression or death, whichever occurred first. OS was defined as the time from start of first-line treatment to death.
Results:
TP53 mutations were observed in 37 (30.1%) patients:10 (27.0%), 6 (16.2%), 9 (24.3%) and 12 (32.4%) in exons 5, 6, 7 and 8, respectively. DCR was 70% in TP53-mutated patients compared to 88% in TP53-wt patients (relative risk, RR: 3.17 [95% CI 1.21-8.48], p=0.019). In particular, a 42% DCR was observed in patients with TP53 exon 8 mutation compared to 87% in exon 8 wt patients (RR 9.6 [2.71-36.63], p<0.001). Shorter median PFS and OS were observed in patients with TP53 exon 8 mutations compared to other patients (4.2 months vs 12.5 months [p=0.058] and 16.2 months vs 32.3 months [p=0.114], respectively); these differences became significant in the subgroup of patients with EGFR exon 19 deletion (4.2 months vs 16.8 months [p<0.001] and 7.6 months vs not reached [p=0.006], respectively), hazard ratio (HR) 6.99 (95% CI 2.34-20.87, p<0.001) and HR 4.75 (95% CI 1.38-16.29, p=0.013), respectively.
Conclusion:
TP53 mutations, in particular exon 8 mutations and those defined as nondisruptive, reduce responsiveness to TKI treatment and induce a worse prognosis in EGFR-mutated NSCLC patients, especially in those carrying exon 19 deletions.
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P3.02b-008 - Quantification and Monitoring of Treatment Response in EGFR Mutant NSCLC Patients by Digital-PCR in Plasma cftDNA (ID 5351)
14:30 - 14:30 | Author(s): L. Crinò
- Abstract
Background:
The identification of activating epidermal growth factor receptor (EGFR) mutations is essential for deciding therapy of non-small cell lung cancer (NSCLC) patients. Circulating cell-free tumor DNA (cftDNA) holds promise as a non-invasive methodology for tumor monitoring in solid malignancies. Among advanced NSCLC patients with an acquired resistance to EGFR-tyrosine kinase inhibitors (TKIs), about 50% carry T790M mutation, but its frequency in EGFR-TKI-naıve patients and dynamic change during therapy remains unclear. We hypothesized that EGFRmutation analysis detection in cftDNA for NSCLC may be feasible for monitoring treatment response to EGFR-TKIs and also predict drug resistance.
Methods:
EGFR sensitive mutations and T790M were analyzed using digital PCR (d-PCR) (Quant studio 3D, life technologies) in longitudinally (at baseline, at 4, 8, 20, 60, 120, 180, 270, 360 days) collected plasma samples (n=50) from 8 tissue-confirmed EGFR-mutant NSCLC patients treated with an EGFR-TKI (Gefitinib N = 4; Erlotinib N = 1; Afatinib N = 3). DNA extracted from plasma of 8 healty blood donors were used to detect the specificity of EGFR mutant assay. Tumor assessment was performed according to RECIST criteria 1.1 every two months.
Results:
The sensitivity of d-PCR in plasma versus tissue was 71.4%. No EGFR mutation was present in the 8 control cases (specificity of 100%). Of four patients who developed progression disease (PD), in the samples of progression, T790M was detected in 75% of cases. The frequency of T790M in pre-TKI plasma samples was of 37.5%. EGFR sensitive mutations decreased at PD while T790M mutation increased in 75% of patients. Patients with concomitant pre-TKI EGFR 19 deletion and T790M showed a PD before of 12 months compared to those with L858R. T790M was frequently detected when new lesions were developed. Four patients had T790M level decreased to undetectable level with longer PFS than those with detectable T790M in blood.
Conclusion:
Our results indicated that d-PCR was a highly sensitive and useful method for detecting the T790M mutation. Moreover, dynamically monitoring T790M change might help determining EGFR-TKI resistance. We thank Italian Association for Cancer Research (AIRC) for supporting the study.
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P3.02b-035 - Cell Free Tumor DNA to Monitor Response to Tyrosine Kinase Inhibitors in Patients with EGFR-Mutant Non-Small Cell Lung Cancer (ID 4038)
14:30 - 14:30 | Author(s): L. Crinò
- Abstract
Background:
Treatment with epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) has improved outcome of EGFR mutant non-small-cell lung cancer (mEGFR-NSCLC) patients. Monitoring the presence of EGFR sensitizing and resistance (such as T790M) mutations in response to treatment may have a clinical impact on the therapeutic strategy. Detecting these alterations in circulating free tumor DNA (cftDNA) can be an easier and more safe way to obtain information about the EGFR mutational status.
Methods:
Analyses have been conducted in NSCLC patients with a tissue-confirmed EGFR mutation, treated in first-line setting with TKIs. EGFR-sensitive and EGFR exon 20 mutations were analyzed in cftDNA extracted from plasma collected at baseline, after 8 and 20 days’ treatment, and every 4 months of therapy until progression. EGFR analyses were performed using PANAmutyper kit (PANAGENE).
Results:
Of the 16 mEGFR-NSCLC patients treated with first-line TKIs to date (4 with gefitinib, 2 with erlotinib and 10 with afatinib), 9 (56%) showed EGFR-sensitivity mutation at baseline in cftDNA: 6 had an exon 19 deletion, 1 an exon 21 L861Q mutation and 2 an exon 21 L858R mutation synchronous to exon 20 mutations (one insertion and one T790M point mutation). In these 2 last patients, exon 20 mutations were not identified in tumor tissue. The baseline mutation became undetectable in cftDNA in all the 6 patients with EGFR exon 19 deletion at different time point from the beginning of TKIs: in 5 patients after 21 days and in 1 after 8 days. All these patients had partial response at the first radiological evaluation. The subject harboring EGFR L858R mutation synchronous to exon 20 insertion was responsive to TKI and showed the disappearance of exon 20 insertion in cftDNA a the first clinical evaluation, whereas EGFR L858R disappeared after 4 cycles of treatment. Patient with EGFR L858R and T790M didn’t respond to TKI and progressed after 2 months of treatment. At present 3 out of 9 patients progressed but only one showed appearance of T790M in cftDNA during TKI. In the 7 mEGFR-NSCLC with undetectable cftDNA mutation at baseline no changes were seen during treatment.
Conclusion:
EGFR mutation analysis in cftDNA could give important information concerning the activity of TKIs. In particular the disappearance of mutation in cftDNA may be an early parameter of response that has to be validated in prospective trials. Moreover, cftDNA may give integrative information with respect to that obtained from tissue analysis, bypassing the problem of tumor heterogeneity.
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P3.02c - Poster Session with Presenters Present (ID 472)
- Event: WCLC 2016
- Type: Poster Presenters Present
- Track: Advanced NSCLC
- Presentations: 4
- Moderators:
- Coordinates: 12/07/2016, 14:30 - 15:45, Hall B (Poster Area)
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P3.02c-068 - Immunotherapy against Non Small Cell Lung Cancer (NSCLC): Looking for Predictive Factors to Avoid an Untargeted Shooting (ID 5207)
14:30 - 14:30 | Author(s): L. Crinò
- Abstract
Background:
The use of immunotherapy for the whole Non Small Cell Lung Cancer (NSCLC) population, is like an untargeted shooting. So trying to discover predicitve factors to response still represents the key to the problem. We retrospectively analyzed a cohort of patients (pts) treated with Nivolumab, in the attempt to correlate clinical and molecular features with response.
Methods:
69 heavily pretreated advanced NSCLCs (16 squamous/ 53 adenocarcinomas) were retrospectively evaluated for response to Nivolumab. Pts’ samples from a subgroup of responders (14/17 pts, 82%), were further analyzed for PD-L1/PD-1 expression by immunoistochemistry (IHC), and for TILs density. We used rabbit monoclonal antibodies anti PD-L1 [clone E1L3N] for tumor cell expression (0-3, negative-intense) and mouse monoclonal antibody anti PD-1 [clone EH33] for TILs.
Results:
Clinico-pathologic characteristics: mostly smoker males (81%), PS 0-1 (85%), EGFR+ 7%, K-RAS+ 23%. Overall response rate was 25% (2% complete response and 23% partial response), stable disease 30%, progressive disease 41%. Median progression free survival (PFS) and overall survival (OS) for the entire cohort were 2.9 and 8.3 months (mo) respectively. 1 and 2-y OS rates were both 44% (95% CI, 29-58). Pts with EGFR + NSCLC showed a significantly lower median OS with respect to the wild type cohort (4.5 vs NR; p < 0.005) as well as pts with brain metastases (4.1 vs NR), while a trend toward improvement in PFS for K-RAS+ was seen. A subgroup analysis according to the time to progression to prior chemotherapy regimen (< 3 mo versus > 6 mo), confirmed a poorer survival for those with rapid spread of disease. Among laboratory tests, a better outcome for those who developed G2 leucopenia was demostrated (OS 8.3 vs 5.0 mo). Severe drug-related adverse events occurred in only 5.7% of pts. PD-L1, PD-1, TIL expression for 14/17 pts with OR, were as follows: PD-L1 > 5% 6/14 pts (43%); PD-1 2/14 (14%); focal TILs presence 7/14 (50%).
Conclusion:
Nivolumab confirms activity in NSCLC with durable responses and accettable safety profile. Of note, 44% of our patients were alive at 2 years. No predictive role emerged in our small cohort, according PD-L1, PD-1 and TILs expression, for those obtaining a tumor response. Interactions among alternative factors such as smoking habit, mutational status, time to progression, bone marrow toxicities (ie leucopenia), may have more powerful association with response and clinical outcome. Updated clinical activity and biomarker analysis will be presented.
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P3.02c-092 - Nivolumab in Multi-Treated Patients with Advanced Sq-NSCLC: Data from the Italian Cohort of Expanded Access Programme (EAP) (ID 4792)
14:30 - 14:30 | Author(s): L. Crinò
- Abstract
Background:
The prognosis of patients with advanced Sq-NSCLC worsens with the increase of the number of treatment linesand no effective therapeutic options were available for those refractory patients so far.Nivolumab demonstrated significant benefits against the SoC docetaxel in 2[nd] line treatment of advanced sq-NSCLC. In the real life experience of the EAP we could assess the clinical activity and tolerability of nivolumab not only in patients treated in 2[nd] line but also in patients who had received at least 2 lines of therapy prior than nivolumab.
Methods:
Nivolumab was provided upon physician request for patients aged ≥18 years who had relapsed after a minimum of 1 prior systemic treatment for stage IIIB/stage IV Sq-NSCLC. Nivolumab 3 mg/kg was administered intravenously every 2 weeks for <24 months. Pts included in the analysis had received ≥1 dose of nivolumab and were monitored for adverse events (AEs) using Common Terminology Criteria for Adverse Events (version 4.03).
Results:
210 patients, corresponding to 56.4% of the entire Italian cohort (n=372), received nivolumab after at least 2 prior lines of chemotherapy in the EAP: 120 (57.1%), 69 (32.9%) and 21 (10%) had received 2, 3 and > 3 prior lines of therapy, respectively. Response was evaluable in 204 patients: with a median number of 8 doses (range, 1–24) and a median follow-up of 5.1 months, the disease control rate was 47%, with 3 patients (1%) in complete response, 30 patients (14%) in partial response and 66 patients (32%) in stable disease. 36 patients (17%) were treated beyond RECIST-defined progression, with 11 of them achieving disease control. As of April 2016, median progression-free survival and median overall survival were respectively 3.8 and 11.2 months. 117/210 patients (55.7%) discontinued treatment for any reason except toxicity; 11 out of 210 (5.2%) discontinued due to AEs.
Conclusion:
These findings showed that nivolumab provided clinical activity with a manageable safety profile in patients with advanced, refractory Sq-NSCLC. These data suggest that nivolumab can be a treatment option for patients failing more than one line of chemotherapy.
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P3.02c-095 - Italian Nivolumab Expanded Access Programme: Efficacy and Safety Data in Squamous Non Small Cell Lung Cancer Patients (ID 5159)
14:30 - 14:30 | Author(s): L. Crinò
- Abstract
Background:
Nivolumab monotherapy has shown survival benefit in patients (pts) with melanoma, lung cancer, renal cell carcinoma and head and neck cancer. The experience of pts and physicians in routine clinical practice is often different from those in a controlled clinical trial setting. Here, we report efficacy and safety of nivolumab monotherapy in pts with squamous non small cell lung cancer (Sq-NCSLC) treated in the nivolumab Expanded Access Programme in Italy.
Methods:
Nivolumab was available upon physician request for pts aged ≥18 years who had relapsed after a minimum of one prior systemic treatment for stage IIIB/stage IV Sq-NSCLC. Nivolumab 3 mg/kg wass administered intravenously every 2 weeks to a maximum of 24 months. Pts included in the analysis had received at least 1 dose of nivolumab and were monitored for adverse events (AE) using Common Terminology Criteria for Adverse Events.
Results:
In total, 371 Italian pts participated in the EAP across 96 centres and 363 patients were evaluable for response. With a median follow-up of 5.2 months (range 0-12.9) and a median of 7 doses, the best overall response rate (BORR) was 18%, with 3 complete responses (CR) and 62 partial responses (PR), and the disease control rate (DCR) was 47%. DCR was comparable among pts regardless previous lines of therapy, brain metastasis, age and smoking habits. A non-conventional benefit was observed in 23 (17 SD and 6 PR) out of 66 pts treated beyond RECIST defined progression. As of April 2016, median progression-free survival and median overall survival were 3.9 (95% CI: 3.2-4.6) and 9.1 (95% CI: 6.7-11.5) months, respectively. Regarding the safety profile, 267 out of 371 pts (72%) had at least one AE of any grade, considered to be drug-related in 106 pts (29%). Grade 3/4 AE were reported in 66 pts and considered to be drug-related in 20 pts (5%). AE were generally manageable following the specific guidelines.
Conclusion:
To date, this is the largest clinical experience with nivolumab in a real-world setting. These preliminary EAP data seems to confirm the efficacy and safety data of nivolumab from registrational trials, supporting its use in current clinical practice for pre-treated pts with Sq-NCSLC.
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P3.02c-096 - Use of Nivolumab in Elderly Patients with Advanced Squamous NSCLC: Results from the Italian Expanded Access Programme (EAP) (ID 5706)
14:30 - 14:30 | Author(s): L. Crinò
- Abstract
Background:
The efficacy and safety of nivolumab in patients with squamous NSCLC (sq-NSCLC) have been demonstrated in several trials including the phase 3, randomized, controlled CheckMate 017 study whose results led to the approval of the product for this indication. However, data on the use of nivolumab in the real world setting is still limited and collecting it is paramount. The Italian nivolumab EAP for sq-NSCLC represents an important source of information in that respect. The current analysis describes results of the use of nivolumab in the group of EAP patients aged >75 years.
Methods:
Nivolumab was provided upon physicians’ request for patients aged ≥18 years who had relapsed after a minimum of one prior systemic treatment for stage IIIB/stage IV Sq-NSCLC. Nivolumab 3 mg/kg was administered intravenously every 2 weeks for <24 months. Patients included in the analysis received ≥1 dose of nivolumab and were monitored for adverse events (AEs) using Common Terminology Criteria for Adverse Events.
Results:
70 out of 372 (18.8%) patients with advanced Sq-NSCLC participating in the EAP in Italy were ≥75 years old and 68 of them were evaluable for response. With a median number of doses of 7 (range, 1–20) and a median follow-up of 4.7 months, the disease control rate was 42.9%, including 13 patients with a partial response and 17 with stable disease. 16 pts were treated beyond RECIST-defined progression and 5 of them achieved disease control. As of April 2016, the median progression-free survival and median overall survival among those elderly patients were 3.2 and 7.6 months, respectively. Among 70 pts, 41 pts (58.6%) discontinued treatment for any reason except toxicity; 8 out of 70 discontinued due to AE (11.4%).
Conclusion:
This analysis, conducted on elderly patients with sq-NSCLC in a real life setting, suggests that nivolumab is an effective and well tolerated treatment for this special population.
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PL03 - Presidential Symposium (ID 428)
- Event: WCLC 2016
- Type: Plenary
- Track:
- Presentations: 1
- Moderators:D.P. Carbone, R. Pirker
- Coordinates: 12/06/2016, 08:35 - 10:25, Hall D (Plenary Hall)
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PL03.07 - First-line Ceritinib Versus Chemotherapy in Patients With ALK-rearranged (ALK+) NSCLC: A Randomized, Phase 3 Study (ASCEND-4) (Abstract under Embargo until December 6, 7:00 CET) (ID 4987)
09:45 - 09:55 | Author(s): L. Crinò
- Abstract
- Presentation
Background:
Here, we report results of ceritinib versus chemotherapy as first-line treatment for advanced ALK+ NSCLC.
Methods:
Untreated ALK+ (IHC confirmed), advanced, nonsquamous NSCLC patients (N=376; median age, 54 years) were randomized (1:1) to ceritinib 750 mg/day (n=189 [59 with brain metastases (BM)]) or chemotherapy (n=187 [62 with BM]; [pemetrexed 500 mg/m[2] plus cisplatin 75 mg/m[2] or carboplatin AUC 5-6] for 4 cycles followed by maintenance pemetrexed), stratified by WHO PS (0 vs 1-2), BM at screening, and prior neo-/adjuvant chemotherapy. Crossover from chemotherapy to ceritinib was allowed at progression (n=80 crossed-over).
Results:
Median treatment exposure was 66.4 weeks for ceritinib and 26.9 weeks for chemotherapy. Median follow-up duration was 19.7 months (randomization to cut-off date). The study met its primary objective, with ceritinib demonstrating statistically significant improvement in BIRC PFS (RECIST 1.1; median, 16.6 [12.6, 27.2] vs 8.1 months [5.8, 11.1], HR=0.55, P<0.001) versus chemotherapy. OS was immature (HR, 0.73 [0.50, 1.08]; P=0.056) with 42.3% of required events at interim analysis. ORR (BIRC, 72.5% vs 26.7%) and DOR (BIRC, median, 23.9 vs 11.1 months) were also higher with ceritinib versus chemotherapy. Among patients with measurable baseline BM and ≥1 postbaseline assessment, intracranial ORR (BIRC neuroradiologist; modified RECIST v1.1) was higher with ceritinib (72.7% [49.8, 89.3] vs 27.3% [10.7, 50.2]) versus chemotherapy (Table). Most common AEs (>50%) with ceritinib were diarrhea (84.7%), nausea (68.8%), vomiting (66.1%), ALT increase (60.3%), and AST increase (52.9%). Overall, 5.3% ceritinib- and 11.4% chemotherapy-treated patients discontinued due to AEs suspected to be drug-related. Figure 1
Conclusion:
First-line ceritinib achieved statistically significant and clinically meaningful improvement in median PFS with an estimated 45% risk reduction in advanced ALK+ NSCLC versus chemotherapy including maintenance. Moreover, ceritinib achieved high and durable systemic responses and high OIRR in patients with measurable BM. Safety profile of ceritinib is consistent with previously reported.
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SH05 - WCLC 2016 Scientific Highlights - Chemotherapy, Targeted Therapy and Immunotherapy of Advanced NSCLC (ID 487)
- Event: WCLC 2016
- Type: Scientific Highlights
- Track: Advanced NSCLC
- Presentations: 1
- Moderators:J. Skřičková, M. Samarzija
- Coordinates: 12/07/2016, 07:30 - 08:30, Hall C1
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SH05.03 - Immunotherapy of Advanced NSCLC (ID 7131)
08:10 - 08:30 | Author(s): L. Crinò
- Abstract
- Presentation
Abstract not provided
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