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Robert Pirker
Moderator of
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MA 10 - Immunotherapy I (ID 664)
- Event: WCLC 2017
- Type: Mini Oral
- Track: Immunology and Immunotherapy
- Presentations: 12
- Moderators:S. Wang, Robert Pirker
- Coordinates: 10/17/2017, 11:00 - 12:30, Room 303 + 304
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MA 10.01 - Durvalumab ± Tremelimumab with Platinum-Doublets in Non-Small Cell Lung Cancer: Canadian Cancer Trials Group Study IND.226 (ID 8700)
11:00 - 11:05 | Presenting Author(s): Desiree Hao | Author(s): R.A. Juergens*, S.A. Laurie, P.M. Ellis, M. Mates, Penelope Bradbury, M. Tehfe, C. Kollmannsberger, A. Arnold, John R Goffin, P. Wheatley-Price, J. Hilton, A.G. Robinson, D. Tu, P. Brown-Walker, L. Seymour
- Abstract
- Presentation
Background:
Anti-PD1-monotherapy has activity in NSCLC with improved outcomes compared to chemotherapy. Preclinical, and early clinical data, suggests that combining immune checkpoint inhibitors and platinum-based chemotherapy may be synergistic. We examined the cohort of patients (pts) with metastatic NSCLC, with no prior therapy for advanced disease, from this multicentre phase Ib trial. The primary objective was to establish the recommend phase II doses of durvalumab (Du) ± tremelimumab (Tr) in combination with platinum-doublet chemotherapy. Secondary objectives included assessing safety, tolerability, and antitumour activity of the 4-drug combination.
Method:
Pts were treated with Du±Tr at one of 4 dose levels (DL) concomitantly with either pemetrexed (Pem) +cisplatin/carboplatin followed by maintenance Pem for nonsquamous histology or gemcitabine (Gem) +cisplatin/carboplatin for squamous tumours. At DL0 Du 15 mg/kg IV q3wks was added; DL1 added Du 15mg/kg q3wk + Tr 1mg/kg x1 dose; DL2a added Du 15mg/kg q3wk + Tr 1 mg/kg q6wk x multiple doses; DL2b added Du 15mg/kg q3wk + Tr 3 mg/kg q6wk (1 dose with cycle 1 and 2 doses with maintenance pem), DL3 and DL4 added a fixed doses of Du 1125mg/Tr 56 mg and Du 1500 mg/ Tr 75 mg q3wk respectively. Du could continue until 1 year or unacceptable toxicity.
Result:
To date, 45 pts (median age=62 (range 36-78); 44% male, 100% ECOG PS≤1) have received 346 cycles in the Pem-platinum cohort while 9 pts (median age=64 (range 57-80); 78% male, 100% ECOG PS≤1) have been received 55 cycles in the Gem-platinum group. Most adverse events were ≤grade 2 and attributed to chemotherapy. Immunotherapy-related adverse events (irAEs) ≥ grade 3 were observed in 27% of patients and were more commonly reported with the addition of Tr. In the Pem-platinum cohort, diarrhea (n=5), fatigue (n=4) and elevated lipase (n=4) were the most come irAEs ≥ grade 3, while rash, pneumonitis and hypothyroidism occurred in 1 pt each after the introduction of Tr. In the Gem-platinum cohort, irAEs ≥ grade 3 were fatigue and rash (1 pt each at DL2b) and elevated lipase (1 pt at DL3). The objective response rate in 35 evaluable patients receiving Pem-platinum was 57.1% (95% CI=39.4, 73.7 ) and 37.5% (95% CI=8.5, 75.5) in the 8 evaluable patients receiving Gem-Platinum.
Conclusion:
The combination of Du±Tr can be safely administered with platinum-doublet chemotherapy with encouraging preliminary response data. Adding Tr may increase ≥ grade 3 irAE hence patient selection and early intervention is key to managing irAEs. *contributed equally
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MA 10.02 - Nab-Paclitaxel + Durvalumab as Second- or Third-Line Treatment of Advanced NSCLC: Results from ABOUND.2L+ (ID 8682)
11:05 - 11:10 | Presenting Author(s): Ramaswamy Govindan | Author(s): Manuel Cobo Dols, S.P. Aix, Pieter E. Postmus, C. Lewanski, Jaafar Bennouna, J.R. Fischer, O.J. Vidal, David James Stewart, A. Ardizoni, J. Weaver, M. Wolfsteiner, Martin Reck, D. Talbot, D. Morgensztern, T.J. Ong
- Abstract
- Presentation
Background:
Chemotherapy may enhance immunotherapeutic effects by causing tumor antigen release, which primes the immune system to kill tumor cells. Early clinical data on nab-paclitaxel + carboplatin in combination with immune checkpoint inhibitors (ICI) demonstrated promising activity without compounding toxicities in patients with non-small cell lung cancer (NSCLC). ABOUND.2L+ evaluated nab-paclitaxel–based regimens in previously treated patients with advanced NSCLC. Here we report the efficacy and safety of nab-paclitaxel + durvalumab as second/third-line treatment.
Method:
Patients with advanced NSCLC were assigned to receive second/third-line (immunotherapy allowed in prior line, including platinum doublet combination) nab-paclitaxel 100 mg/m[2] on days 1 and 8 + durvalumab 1125 mg on day 15, in 21-day cycles, administered until unacceptable toxicity/progression per immune-related RECIST v1.1. Primary endpoint is progression-free survival (PFS). Secondary endpoints are overall survival (OS), overall response rate (ORR), disease control rate (DCR), and safety.
Result:
Seventy-nine patients were enrolled. Median age was 63 years, 68% of patients were male, 23% had Eastern Cooperative Oncology Group performance status of 0, and 70% had nonsquamous NSCLC; 11% of patients received prior ICIs. Median PFS (Table) and OS were 4.5 (3.4-5.8) months and NE (7.3-NE). ORR was 27% (1 complete response) and DCR was 71%. Grade 3/4 treatment-emergent adverse events of special interest occurring in ≥ 5% of patients included neutropenia (6%) and dyspnea (5%); grade 3/4 peripheral neuropathy and anemia each occurred in 4% of patients. Median treatment duration was 24 weeks; median number of treatment cycles was 7. For nab-paclitaxel and durvalumab, median dose intensities were 59.05 mg/m[2]/week and 326.61 mg/week, respectively; median percentages of per-protocol dose were 88.58% and 87.10%.
Conclusion:
The combination of durvalumab with nab-paclitaxel demonstrated antitumor activity with manageable toxicity in the second/third-line setting. Further details will be presented. NCT02250326Nab-P Durva Median PFS (range), months Overall (n = 79) 4.5 (3.4-5.8) ICI pretreated (n = 9)[a] ICI naive (n = 69)[a] 6.9 (1.4-NE) 4.4 (3.0-5.7) Squamous (n = 23)[a] Nonsquamous (n = 55)[a] 5.9 (3.0-7.8) 4.2 (2.9-5.7) ICI, immune checkpoint inhibitor; NE, not estimable; PFS, progression-free survival. [a] Data pending for 1 patient.
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MA 10.03 - 3-Year Survival and Duration of Response in Randomized Phase II Study of Atezolizumab vs Docetaxel in 2L/3L NSCLC (POPLAR) (ID 8703)
11:10 - 11:15 | Presenting Author(s): Keunchil Park | Author(s): C. Lewanski, Shirish M Gadgeel, L. Fehrenbacher, Julien Mazieres, A. Rittmeyer, Ji-Youn Han, A. Artal-Cortes, F. Braiteh, M. Gandhi, W. Yu, C. Matheny, P. He, A. Sandler, M. Ballinger, Johan F. Vansteenkiste
- Abstract
- Presentation
Background:
Atezolizumab (anti–PD-L1) has demonstrated OS benefit over docetaxel in a randomized Phase II study, POPLAR, in patients with advanced NSCLC. This benefit has been confirmed in the randomized Phase III study OAK (Rittmeyer, 2017). The 3-year survival analysis of the POPLAR study presented here describes the longest survival follow-up reported to date of an all-comer randomized PD-L1/PD-1 immunotherapy trial in 2L+ NSCLC.
Method:
Patients were randomized 1:1 to receive atezolizumab (1200 mg) or docetaxel (75 mg/m[2]) IV q3w. Tumors were prospectively evaluated for tumor cell (TC) or tumor-infiltrating immune cell (IC) PD-L1 expression using the VENTANA SP142 IHC assay. Landmark OS was estimated using the Kaplan-Meier method. Data cutoff, April 7, 2017; minimum follow-up, 3 years.
Result:
The 2-year and 3-year survival with atezolizumab vs docetaxel were 32.2% vs 16.6% and 18.7% vs 10.0%, respectively. The long-term OS benefit of atezolizumab vs docetaxel was observed across histology and PD-L1 expression subgroups (Table). While the TC3 or IC3 subgroup derived the greatest OS benefit, the TC0 and IC0 subgroup also had improved long-term OS with atezolizumab vs docetaxel. The ITT ORR was 15% in both atezolizumab and docetaxel arms, but the median duration of response was 3 times longer with atezolizumab (22.3 months [95% CI: 11.6, 31.1] vs 7.2 months [95% CI: 5.8, 12.2] with docetaxel). Seven of the 11 docetaxel-arm 3-year survivors received subsequent non-protocol therapy with anti–PD-L1/PD-1 agents. Atezolizumab had a favorable safety profile compared with docetaxel that was consistent with previous reports.
Conclusion:
Atezolizumab demonstrates superior 2-year and 3-year OS benefit compared with docetaxel, and this benefit is observed across histology and PD-L1 expression subgroups (including TC0 and IC0). Atezolizumab is well tolerated, and responses are highly durable. These results are consistent with long-term OS results from OAK, presented separately.Table. Landmark OS in the ITT, PD-L1 expression, and histology subgroups in POPLAR Population (n, atezolizumab vs docetaxel) 2-year OS rate, % 3-year OS rate, % Atezolizumab Docetaxel P value[a] Atezolizumab Docetaxel P value[a] ITT (144 vs 143) 32.2% 16.6% 0.0027 18.7% 10.0% 0.0419 PD-L1 Expression Subgroups TC3 or IC3 (24 vs 23) 41.7% 19.9% 0.1003 37.5% 14.9% 0.0724 TC2/3 or IC2/3 (50 vs 55) 36.1% 13.8% 0.0082 21.2% 9.9% 0.1166 TC1/2/3 or IC1/2/3 (93 vs 102) 36.0% 19.8% 0.0124 18.0% 11.0% 0.1759 TC0 and IC0 (51 vs 41) 25.0% 6.8% 0.0202 20.5% 6.8% 0.0693 Histology Subgroups Non-squamous (95 vs 95) 32.2% 21.1% 0.0960 23.3% 12.4% 0.0585 Squamous (49 vs 48) 32.7% 7.8% 0.0020 9.4% 5.2% 0.4603 [a ]For descriptive purpose only. TC3 or IC3 = PD-L1 ≥ 50% TC or 10% IC; TC2/3 or IC2/3 = PD-L1 ≥ 5% TC or IC; TC1/2/3 or IC1/2/3 = PD-L1 ≥ 1% on TC or IC; TC0 and IC0 = PD-L1 < 1% on TC and IC. NCT01903993.
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MA 10.04 - Discussant - MA 10.01, MA 10.02, MA 10.03 (ID 10824)
11:15 - 11:30 | Presenting Author(s): Wan-Teck Lim
- Abstract
- Presentation
Abstract not provided
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MA 10.05 - Improved Outcome for Immune Checkpoint Inhibitors (ICI) in Patients Previously Treated with Bavituximab in the SUNRISE Trial (ID 8684)
11:30 - 11:35 | Presenting Author(s): Michael Boyer | Author(s): David R Spigel, P. Mainwaring, H. Lena, M. McCleod, G. Losonczy, R.E. Sanborn, R. Natale, M. Tang, J. Lai, N.L. Kallinteris, Joseph Shan, David E Gerber
- Abstract
- Presentation
Background:
Bavituximab targets exposed phosphatidylserine (PS) in the tumor microenvironment, resulting in repolarization of myeloid suppressor cells/M2 macrophages to M1, production of pro-inflammatory cytokines such as IFNγ and IL-12, dendritic cell maturation, and tumor specific cytotoxic T-cell activation. SUNRISE was a Phase III trial of docetaxel with bavituximab (D+B) or placebo (D+P) in patients with treated Stage IIIb/IV non-squamous NSCLC. Recent correlative analyses from SUNRISE suggest bavituximab is more active in PD-L1 negative, immune cold tumors and thus may complement PD-1/PD-L1 ICI.
Method:
This subgroup analysis included all patients who received subsequent ICI after discontinuing SUNRISE study drug. We calculated overall survival (OS) both from randomization and start of subsequent ICI.
Result:
Ninety-three of 597 randomized patients (16%) received ICI as next line of therapy after SUNRISE assigned treatment. Baseline characteristics were balanced between the treatment groups and consistent with the ITT population. From randomization, mOS was not reached (95% confidence interval [CI], 15.2-NA) in D+B (N=46) and 12.6 months (95% CI, 10.4-17.8) in D+P (N=47) (hazard ratio [HR], 0.46; P=0.006) (Figure). From start of ICI, mOS was not reached (95% CI, 10.2-NA) in D+B and 6.2 months (95% CI, 3.9-8.7) in D+P (HR, 0.42; P=0.002). The mPFS was 6.0 months (95% CI, 3.5-6.5) in D+B and 4.4 months (95% CI, 2.6-6.3) in D+P (HR, 1.00; P=0.991). ORR was 20% vs. 13% (Odds ratio 0.6; P=0.41) for D+B and D+P, respectively. The safety profile was similar between groups and no immune related (IR) toxicities (colitis, pneumonitis, hypothyroidism) were reported.
Conclusion:
Within the limits of a subgroup analysis, a significant improvement in OS was observed for patients previously treated with D+B. Furthermore, bavituximab has not been associated with IR toxicities and might serve as a useful drug in combination with ICI for the treatment of immune cold tumors. Figure 1
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MA 10.06 - Real-World Results in Non-Squamous Non-Small Cell Lung Cancer Patients: Italian Nivolumab Expanded Access Programme (ID 9580)
11:35 - 11:40 | Presenting Author(s): Francesco Grossi | Author(s): Lucio Crinò, A. Delmonte, D. Turci, D. Signorelli, F. De Marinis, H.J. Soto Parra, Domenico Galetta, Frederico Cappuzzo, F. Sperandi, M. Tiseo, G. Puppo, F. Roila, Maria Rita Migliorino, G. Tonini, F. Cognetti, A. Santoro, D. Tassinari, A. Scoppola, D. Giannarelli, Enrico Cortesi
- Abstract
- Presentation
Background:
Nivolumab monotherapy has shown survival benefit in patients (pts) with different tumors, including melanoma, lung cancer, renal cell carcinoma, head and neck cancer and Hodgkin lymphoma. Controlled clinical trial setting differs from what experienced by pts and physicians in routine clinical practice. Here, we report efficacy and safety results of nivolumab in pts with non-squamous non-small cell lung cancer (Non-Sq-NSCLC) treated in the Expanded Access Programme in Italy.
Method:
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 non-Squamous NSCLC. Nivolumab 3 mg/kg was administered intravenously every 2 weeks to a maximum of 24 months. Pts included in the analysis had received at least one dose of nivolumab and were monitored for adverse events (AE) using Common Terminology Criteria for Adverse Events.
Result:
Overall, 1588 pts were enrolled in the EAP across 168 Italian centers. Baseline characteristics of pts were representative of Non-Sq-NSCLC population, in the advanced disease setting. As of March 2017, median overall survival (OS) was 11 months (10.0-12.0), with a median follow-up of 7.8 months (1-21.9) and a median of 7 doses (1-46). The best overall response rate (BORR) was 18%, including 10 pts (<1%) with complete response and 280 pts (17.6%) with partial response. Stable disease has been defined for 414 pts (26.0%) and totally 274 (17.2%) patients were treated beyond progression. Response rates and survival were comparable among pts regardless age (< and ≥ 75 years), presence of brain metastasis and number of prior therapies. Overall, among 1588 pts, 1254 discontinued treatment for any reason, with only 93 (7%) pts who discontinued treatment due to adverse events, in line with what observed in previous studies.
Conclusion:
To date, this is the largest clinical experience with nivolumab in a real-world setting and these EAP data are in line with what reported in the registrative phase 3 clinical trial. According to these results, nivolumab seems to be an effective and safe therapy for pre-treated patients with non-squamous NCSLC, supporting its use in current clinical practice.
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MA 10.07 - Elderly Lung Cancer Patients on Immunotherapy: Preliminary Results from the ELDERS Study (ID 9840)
11:40 - 11:45 | Presenting Author(s): Fabio Gomes | Author(s): S. Woolley, R. Califano, Y. Summers, K. Baker, K. Burns, J. Yorke, Fiona Blackhall
- Abstract
- Presentation
Background:
Immunotherapy is revolutionising the way many cancer types are treated. The immunosenescence and the high heterogeneity of the elderly raises questions on the benefits with such treatments and real-world data is lacking.
Method:
ELDERS is a prospective, observational pilot study on the use of checkpoint inhibitors in patients with advanced/metastatic non-small cell lung cancer (NSCLC) or malignant melanoma. The study was designed with 2 arms, the elderly (≥ 70 years) and the non-elderly (45-69 years) with 2 co-primary endpoints, immune-related toxicity (irAE) profile and health-related quality of life (HRQoL) through the EORTC QLQ-C30. A comorbidity score (CIRS) was applied at baseline (score 0-56) and serial geriatric assessments were performed for stratification with a screening tool (G8) and further geriatric assessment as needed. A total of 110 patients of a planned 120 have been recruited. This interim analysis is of the NSCLC cohort with a minimum of 3 months on study/follow-up.
Result:
32 patients were included, with 96% treated with pembrolizumab (9% first-line) and 40.6% enrolled on the elderly arm. In both arms, 45% had a tumour PD-L1 expression of ≥50%. The elderly arm had more advanced disease with 69% staged M1b vs. 42.1% in younger arm (p=0.05). 69% of patients, in both arms, were performance status 0/1 at the start of treatment. The median CIRS total score was 12 for the elderly and 7 for the younger arm. 46% of elderly patients had an abnormal geriatric screening (G8≤14), requiring further assessments. With a median follow-up of 6 months, the objective response rate (ORR) was overall 19% with a median time to response of 8 weeks. The ORR was numerically higher in the elderly with 30.8% vs. 10.5% (p=0.09). 9.4% of patients on study had a grade 3/4 irAE, with no difference between study arms. Elderly patients had a numerically higher rate of admissions, 53.8% vs. 36.8% (p=0.18). No statistically significant correlation was identified between higher comorbidity score or abnormal geriatric assessment and the incidence of irAEs. No significant negative impact on the global HRQoL was detected in either arm during treatment with immunotherapy.
Conclusion:
Despite the small number of patients and the limited follow-up time, there is no signal in this interim analysis to indicate that elderly patients have less benefit or higher risk of irAE compared with younger patients, despite more comorbidities and geriatric syndromes. These results help to inform clinical practice in the absence of trials dedicated to the elderly population.
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MA 10.08 - Discussant - MA 10.05, MA 10.06, MA 10.07 (ID 10825)
11:45 - 12:00 | Presenting Author(s): Hidehito Horinouchi
- Abstract
- Presentation
Abstract not provided
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MA 10.09 - Increased T Follicular Helper Cell Infiltration in Lung Adenocarcinoma Tertiary Lymphoid Organs (ID 8487)
12:00 - 12:05 | Presenting Author(s): Erin Anne Marshall | Author(s): K.W. Ng, Katey S.S. Enfield, S.D. Martin, K. Milne, S.H.Y. Kung, C.E. Macaulay, W.L. Lam
- Abstract
- Presentation
Background:
T follicular helper cells (Tfh) are an antigen-experienced CD4+ T cell subset that have been found to play crucial roles in the development of humoral immunity. In particular, their presence in the B cell-rich germinal centre of secondary and tertiary lymphoid tissue aids in B cell maturation through selection of B cells producing high-affinity antibodies. Tfh cells have known roles in autoimmune disease and B cell malignancies; however, their role in many solid tumours, including those of the lung, remains unclear.
Method:
We analyzed 83 paired tumour-normal lung adenocarcinoma samples from the BC Cancer Agency (BCCA) as well as 576 unpaired samples from The Cancer Genome Atlas (TCGA). Relative immune cell content was obtained from gene expression data using a linear support vector regression deconvolution approach (CIBERSORT). Spatial positioning of B and T cells within selected tumour sections was examined through IHC. The impact of Tfh infiltration on patient survival was analyzed using a Cox Proportional Hazard model.
Result:
T follicular helper cells are increased in tumour tissue, accompanied by global upregulation of Tfh markers PDL1 and CXCR5 in both the BCCA and TCGA cohorts. Histological analysis revealed localization of Tfh cells within tertiary lymphoid organs, with direct contact with B cells in the follicular zone observed. Importantly, Tfh recruitment appears to be an early event in tumour development and a function of neoantigen exposure, indicative of an active anti-tumour response rather than a result of chronic inflammation of the tumour microenvironment.
Conclusion:
T follicular helper cells are required for B cell maturation and subsequent antibody responses. As such, it is not surprising that Tfh infiltration in tumour-resident ectopic lymphoid structures correlates with patient survival in various cancer types. Given the importance of tumour-specific antibody responses in natural and therapeutic immunity, further investigation of Tfhs may show prognostic utility and be a marker of early-stage lung tumours.
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MA 10.10 - Tumor Draining Lymph Node Immunophenotype Corresponds with Primary Tumor Characteristics in Patients with Non-Small Cell Lung Cancer (ID 10343)
12:05 - 12:10 | Presenting Author(s): Daniel H. Sterman | Author(s): V. Murthy, J.J. Tsay, J. Minehart, K. Mangalick, J.L. Bessich, G.C. Michaud, M.A. Curotto De Lafaille, Kwok-Kin Wong, C. Goparaju, Harvey I Pass
- Abstract
- Presentation
Background:
There is growing appreciation for the role of tumor-draining lymph nodes (TDLN) in the dynamic of immunoediting orchestrated by non-small cell lung cancers (NSCLC). By comparing T-cell subsets and gene expression in TDLN and non-draining lymph nodes (NDLN), we aim to determine whether there is tumor-regional variation in immunophenotype.
Method:
Patients undergoing endobronchial ultrasound-guided transbronchial needle aspiration for the diagnosis/staging of NSCLC were recruited. Aspirates were obtained from TDLN (N1/N2 nodes with increased fluorodeoxyglucose-F-18 (FDG) avidity and/or enlarged >1cm) and NDLN (non-enlarged/non-FDG-avid N2/N3 nodes) along with peripheral blood. Samples were stained with fluorophore-conjugated antibodies (CD4-FITC, CD8-V450, CD25-PECy7, CD127-APCR700, CD45RO-PECF594) and analyzed by flow cytometry. CD4+CD25- and CD8+ effector T-cells (Teff) were sorted. Gene expression profiling was performed on sorted Teff using the Nanostring™ platform to measure differential expression between TDLN and NDLNs.
Result:
We compared T-cell subpopulations in TDLN and paired NDLN from 16 subjects. There were significantly fewer CD4+ T-cells in TDLN vs NDLN (10.1% vs 28.9%, p=0.0039), with more Tregs (12.1% vs 7.3%, p=0.1563) suggesting a pattern of tumor-regional immunosuppression in the TDLN. This was more consistent when tumor histology was adenocarcinoma compared to squamous cell cancer with respect to both depletion of Teff and higher proportion of Tregs (Figure 1). A more immunosuppressive TDLN phenotype was also observed with high tumor PD-L1 expression (>50%), with 36% fewer CD4+ T-cells in TDLN relative to paired NDLN when PD-L1 expression was high relative to just 3.2% fewer CD4+ T-cells with low PD-L1 expression. Gene expression in Teff has preliminarily demonstrated upregulation of genes mediating T-cell exhaustion (CTLA-4, PD-1, TGF-β) and downregulation of co-stimulatory/recruitment factors (CD28, ICOS, ICAM2) in TDLN suggesting impaired activation of tumor-regional Teff. Figure 1
Conclusion:
Our findings suggest that TDLNs in patients with NSCLC display a tolerogenic phenotype, with more marked immunosuppression in the setting of adenocarcinoma and high tumor PD-L1 expression.
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MA 10.11 - Hyperprogressive Disease (HPD) Is Frequent in Non-Small Cell Lung Cancer (NSCLC) Patients (Pts) Treated with Anti PD1/PD-L1 Agents (IO) (ID 10222)
12:10 - 12:15 | Presenting Author(s): Roberto Ferrara | Author(s): C. Caramella, M. Texier, C. Audigier-Valette, L. Tessonnier, Laura Mezquita, J. Lahmar, Julien Mazieres, G. Zalcman, S. Brosseau, Virginie Westeel, S. Le Moulec, L. Leroy, B. Duchemann, C. Lefebvre, R. Veillon, S. Champiat, C. Fertè, David Planchard, Marie-Eve Boucher, G. Martinez-Bernal, E. Bria, G. Tortora, J. Soria, Benjamin Besse
- Abstract
- Presentation
Background:
Using Tumor Growth Rate (TGR), HPD was identified in 9% of 131 advanced cancer pts, treated with IO in a single institution (Champiat et al. 2017). In this study, we explored HPD in a large, multicenter cohort of advanced NSCLC pts treated with IO.
Method:
We performed a retrospective analysis of consecutive NSCLC pts treated with IO, in 8 institutions, between November 2012 and April 2017. Eligibility criteria required, for each patient: 2 CT scans performed before starting IO and one during IO, an interval between two CT scans ≥2 weeks or 3 months (m) and presence of target lesions. CT scans were centrally assessed according to RECIST 1.1 criteria. We calculated TGR before IO (TGR pre-IO) and during IO (TGR IO); patients were defined HPD if they had progression disease (PD) at first evaluation during IO and a ≥ 2-fold increase in the TGR IO compared to TGR pre-IO. Median overall survival (mOS) was estimated using Kaplan-Meier method for the total population and HPD pts.
Result:
Among 419 eligible pts, 86 were excluded for inadequate intervals between CT scans. Among 333 evaluable pts, 63% were male, 46% ≥65 years, 43% smokers; 12% had PS ≥ 2, 65% adenocarcinoma, 45% ≥3 metastatic sites, 22% KRAS mutation, 4% EGFR mutation, 1% ALK rearrangement; 21% had PD-L1 positive status, 10% negative, 69% unknown, >90% received single agent PD-1 inhibitor in ≥ 2 line. Response rate (RR) to IO was 18%, median follow up was 12 m [10-14]. 33% of pts had TGR IO ≥1 (not regressing tumors), 25% had TGR IO ≥ 2-fold TGR pre-IO and 54 pts (16%) had HPD. 15 pts (4%) had confirmed pseudoprogression, 3 were initially qualified as HPD. Compared to not-HPD, HPD pts had more frequently ≥ 3 metastatic sites at baseline (59% vs 43% p=0,02) and more new lung lesions during IO (34% vs 17% p=0,007). PD-L1 negative status was more common among HPD pts but the association was borderline significant (53% vs 28% p=0,05). Age, clinical, molecular characteristics, RR to treatment before IO, baseline tumor burden, liver or brain new lesions during IO were not different according to HPD status. mOS was 13 m [10-17] in the total population, 5 m [3-8] in HPD pts.
Conclusion:
HPD occurred in 16% of advanced NSCLC pts treated with IO and was associated with plurimetastatic disease and appearance of new lung lesions. Further work is needed to characterize HPD prognostic value.
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MA 10.12 - Discussant - MA 10.09, MA 10.10, MA 10.11 (ID 10826)
12:15 - 12:30 | Presenting Author(s): David E Gerber
- Abstract
- Presentation
Abstract not provided
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MS 20 - Value-based Management for Special Populations (ID 542)
- Event: WCLC 2017
- Type: Mini Symposium
- Track: Nursing/Palliative Care/Ethics
- Presentations: 1
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MS 20.02 - Value-Based Judgment in Advanced NSCLC: The European Perspective (ID 7738)
11:20 - 11:40 | Presenting Author(s): Robert Pirker
- Abstract
- Presentation
Abstract:
Therapy of lung cancer depends on many factors including tumor-related factors, patient parameters and treatment-related factors. Tumor-related factors are histological subtype, molecular characteristics and stage as well as growth of tumors. Patient-related factors include age, life expectancy, gender, performance status, organ functions, co-morbidity, functional status, geriatric syndromes and patient preference. Drug-related parameters include convenience of administration, side effects of drugs, and polypharmacy. Costs, cost effectiveness and value-based judgements are also of major importance. Value-based judgements of anticancer therapies are based on the magnitude of the clinical benefit balanced against their costs (1). These judgements are gaining increasing importance because of the increasing costs of modern anticancer treatments including novel anticancer drugs. The benefit of treatments focus on living longer and living better. The evidence of the magnitude of the treatment benefit is derived from clinical trials such as phase 3 trials or from meta-analyses of randomized trials. Important outcome parameters focus on the impact of the treatments on overall survival, progression-free survival, response rates and symptom relief. Parameters for living longer are improved overall survival and/or improved surrogate of overall survival such as disease-free survival in the adjuvant setting or progression-free survival. With regard to living better, important parameters are improved quality of life, improved surrogate of quality of life, and reduced toxicity. The incremental cost-effectiveness ratio (ICER) is often used to evaluate the value of a new anticancer drug (2, 3). ICER refers to the costs per life year gained or costs per quality-adjusted life year gained. A drug is considered cost-effective if its ICER is below a certain threshold which depends on the country and may range from about 20.000 to 50.000 Euros or even higher. Several scientific and professional societies including ESMO have developed scales to determine the clinical benefit of systemic treatments in patients with cancer. The ESMO - Magnitude of Clinical Benefit Scale (ESMO-MCBS) is a standardized, generic, validated tool to assess the magnitude of clinical benefit that can be expected form anticancer therapies (4, 5). This tool is dynamic and has been planned to be revised in regular intervals (4). Separate tools have been developed for the adjuvant and the palliative settings. For assessment of survival data, hazard ratios and median survival times are considered. Based on simulation data, the lower limit of the 95% confidence interval of the hazard ratios have been recommended for use (4). Form 1 of the ESMO-MCBS is used for adjuvant or neoadjuvant therapies and for localized or metastatic disease treated with curative intent (4). The grades are A, B and C, with grades A and B representing high levels of clinical benefit (4). Grade A refers to >5% improvement in survival or improvement in disease-free survival alone with a HR<0.65 in studies without mature survival data. Grade B refers to ≥3% but ≤5% improvement in survival or improvement in disease-free survival alone with hazard ratios <0.65-0.8 without mature survival data. In addition, non-inferior survival or disease-free survival with reduced treatment toxicity or improved quality of life, or non-inferior survival with reduced treatment costs are also graded as B. Grade C refers to <3% improvement of survival or improvement in disease-free survival alone with hazard ratios >0.8 in studies without mature survival data. Form 2 of the ESMO-MCBS is used for therapies without curative intent (4). The grades range from 1 to 5, with grades 4 and 5 representing high levels of proven clinical benefit (4). Form 2 is more complex and includes forms 2a, 2b and 2c. Form 2a is for therapies that are not likely to be curative and have overall survival as primary endpoint. Form 2b is for therapies that are not likely to be curative and have progression-free survival as primary endpoint. Form 2c is for therapies that are not likely to be curative and have primary endpoints other than overall survival or progression-free survival. The preliminary magnitude of clinical benefit is based on the efficacy of the treatment and is then adjusted according to quality of life and grade 3-4 toxicities. The preliminary score is upgraded by 1 if the treatment resulted in improved quality of life and/or less grade 3-4 toxicities. The ESMO-MCBS is planned for comparative analyses of different treatments (4, 5). The value of treatments of lung cancer measured according to the ESMO-MCBS in a single institution has recently been published (6). In summary, the evaluation of the clinical benefit of anticancer therapies in patients with lung cancer is a complex and rapidly moving area. It is based on the evidence from clinical trials, cost effectiveness analyses and, more recently, also valued-based judgements. The latter tools are dynamic and balance magnitudes of the benefits against the costs of specific treatments. Despite all these measures, clinically experienced doctors working in close co-operation with informed patients and their relatives are crucial for optimal treatment decisions in patients with lung cancer. References 1. Porter ME. NEJM 2010, 363, 2477 2. Dilla T et al. Patient Preference and Adherence 2016, 10, 1 3. Bae YHJ & Mullins CD. J Manag Care Pharm 2014, 20, 1086 4. Cherny NI et al, Ann Oncol 2015, 26, 1547 5. Cherny NI et al. ESMO Open 2016, 1, e000100 6. Kiesewetter B et al. ESMO Open 2016, 1, e000066
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P2.09 - Mesothelioma (ID 710)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Mesothelioma
- Presentations: 1
- Moderators:
- Coordinates: 10/17/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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P2.09-004 - PD-L1 Protein Expression Is Negative Prognostic Factor in Malignant Pleural Mesothelioma in Central Europe (ID 9558)
09:30 - 09:30 | Author(s): Robert Pirker
- Abstract
Background:
Early data on immune-checkpoint blockade with PD-1 inhibitors show promising response rates and survival benefit mainly in PD-L1 positive malignant pleural mesothelioma (MPM) patients. Reported rate of PD-L1 positivity of MPM is between 20-40%. However, the role of PD-L1 protein expression positivity in prediction of a response to PD-1/PD-L1 inhibitors remains controversial. We assessed the prognostic value of PD-L1 expression in patients with MPM in central Europe.
Method:
We evaluated protein expression of PD-L1 in formalin-fixed paraffin-embedded surgical specimens of 176 MPM patients from Austria, Croatia, Hungary and Slovenia. PD-L1 antibody clone E1L3N (Cell Signaling) was used. Cut-off point of >10% of PD-L1-positive tumor cells at any staining intensity was correlated with clinicopathologic characteristics (age, gender, IMIG clinical stage, histology (epithelioid vs non-epithelioid) and survival).
Result:
There were altogether 49 females and 127 males, median age 63 years. PD-L1 protein expression of >10% was observed in higher proportion in a patient with higher IMIG stage (III+IV vs. I+II), as well as in patients with non-epithelioid histology, later being also statistically significant (p=0.0026). Median survival of patients with high PD-L1 expression (>10%) in tumor cells was significantly shorter in comparison with patients demonstrating lower PD-L1 expression (26 vs. 67 weeks respectively, p<0.001). PD-L1 expression (>10%) proved to be an independent prognostic factor in a multivariate cox regression analysis (hazard ratio [HR] 2.902; 95% confidence interval [CI] 1.425 to 5.937; p = 0.003).
Conclusion:
High expression of PD-L1 on tumor cells (>10%) is negative independent prognostic factor in malignant pleural mesothelioma regardless of histology.
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SH 02 - WCLC 2017 Highlights of the Previous Day (ID 752)
- Event: WCLC 2017
- Type: Scientific Highlights
- Track: Biology/Pathology
- Presentations: 1
- Moderators:
- Coordinates: 10/17/2017, 07:00 - 08:00, Room 503
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SH 02.01 - Chemotherapy/Targeted Therapy and SCLC/Neuroendocrine Tumors (ID 10927)
07:00 - 07:20 | Presenting Author(s): Robert Pirker
- Abstract
- Presentation
Abstract not provided
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