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K. Reckamp
Moderator of
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ORAL 18 - Non PD1 Immunotherapy and Angiogenesis (ID 114)
- Event: WCLC 2015
- Type: Oral Session
- Track: Treatment of Advanced Diseases - NSCLC
- Presentations: 7
- Moderators:C. Butts, K. Reckamp
- Coordinates: 9/08/2015, 10:45 - 12:15, Four Seasons Ballroom F1+F2
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ORAL18.01 - TG4010 Immunotherapy plus Chemotherapy as First Line Treatment of Advanced NSCLC: Phase 2b Results (ID 669)
10:45 - 10:56 | Author(s): E. Quoix, F. Forget, C. Chouaid, Z. Papai, G. Losonczy, E. Felip, M. Cobo, C. Ottensmeier, J.T. Beck, B. Bastien, A. Tavernaro, G. Lacoste, J. Limacher, H. Léna
- Abstract
- Presentation
Background:
TG4010 is an immunotherapy using an attenuated and modified poxvirus (MVA) coding for MUC1 and interleukin-2. Previous Phase 2 trials have demonstrated the efficacy and safety of TG4010 in combination with chemotherapy. In addition, Triple Positive Activated Lymphocytes (TrPAL; CD16+, CD56+, CD69+) was identified as a potential biomarker predictive of efficacy
Methods:
TIME is a double blind, placebo-controlled phase 2b/3 study. The Phase 2b part compared first line chemotherapy combined with TG4010 or placebo and further assessed the predictive value of baseline level of TrPAL. Eligibility criteria included stage IV NSCLC not previously treated, MUC1+ tumor by immunohistochemistry, PS ≤1. TG4010 10[8] pfu or placebo was given SC weekly for 6 weeks (w), then every 3w up to progression in immediate combination with chemotherapy. Patients were randomized using TrPAL cut-off value (normal vs high) that was previously pre-determined in healthy subjects. Primary efficacy endpoint was progression-free survival (PFS) using a Bayesian design to confirm that, with a 95% probability, the true hazard ratio (HR) is <1 in patients with normal TrPAL level. Secondary objectives were response rate (ORR), duration of response, survival, safety and subgroup analyses according to histology and level of TrPAL.
Results:
222 patients (pts) were randomized 1:1. In pts with normal TrPAL the study met the primary endpoint with a Bayesian probability of 98.4% that the PFS HR is <1 in favor of TG4010. In the whole study population, ORR was 39.6% vs 28.8% and duration of response was 30.1w versus 18.7w in the TG4010 and placebo arms respectively. Survival data will be presented at the time of the meeting. Preplanned subgroup analyses showed that PFS was significantly improved in the TG4010 arm in pts with low TrPAL (n=152; HR=0.66 [CI95% 0.46-0.95] p= 0.013) while it was not the case in pts with high TrPAL (n=70; HR=0.97 [CI 95% 0.55-1.73] p=0.463). In addition, PFS was also significantly improved in pts with non-squamous tumors (n=196; HR=0.69 [CI95% 0.51-0.94] p=0.009) as well as in pts with non-squamous tumors and low TrPAL (n=131; HR=0.61 [CI95% 0.42-0.89] p=0.005). In this last group, PFS at 9 months was 37% with TG4010 versus 18% with placebo. Frequency and severity of adverse events were similar in both treatment arms except injection site reactions which were more frequent in the TG4010 arm but all of mild or moderate intensity. Exploratory analysis of the impact of PDL1 expression in the tumor of patients treated with TG4010 in TIME study supports the activity of TG4010 whether the tumor is positive or negative for PDL1 expression.
Conclusion:
These results provide additional data supporting the efficacy of TG4010, particularly in patients with non-squamous tumors and/or a low level of TrPAL at baseline. The Phase 3 part of the TIME study is planned to continue in patients with non-squamous tumors with OS as primary endpoint.
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ORAL18.02 - MUC1-Targeted Dendritic Cell-Based Vaccine Immunotherapy in Patients with Standard Treatments-Refractory Non-Small-Cell Lung Cancer (ID 1193)
10:56 - 11:07 | Author(s): K. Teramoto, J. Hanaoka, N. Tezuka, Y. Daigo
- Abstract
- Presentation
Background:
MUC1, a tumor antigen, has been considered to a promising target antigen for cancer immunotherapy because it possesses a potent immunogenicity. It is processed and presented by antigen-presenting cells in a MHC-unrestricted pattern. Dendritic cell-based vaccine immunotherapy can elicit antigen-specific cytotoxic T lymphocytes in tumor-bearing hosts, and activated cytotoxic T lymphocytes are expected to attack cancer cells. In this study, we evaluated the efficacy of MUC1-targeted dendritic cell-based vaccine immunotherapy in patients with standard treatments-refractory advanced non-small-cell lung cancer (NSCLC).
Methods:
The eligibility criteria of this immunotherapy were as follows: histologic or cytologic evidence of NSCLC that had been proven to express MUC1 abundantly; an Eastern Cooperative Oncology Group performance status of 0-2; advanced stage of diseases refractory for other standard cancer treatments. The dendritic cells were prepared from peripheral blood mononuclear cells with cytokines interleukin-4 and granulocyte macrophage colony stimulating factor, were pulsed with MUC1 peptides, and subsequently administered to patients subcutaneously. The vaccinations were repeated bi-weekly, and assessable patients were received at least 6 vaccinations. Tumor response was assessed according to the Response Evaluation Criteria in Solid Tumors. Adverse events were graded according to National Cancer Institute Common Toxicity Criteria.
Results:
From June 2005 and March 2015, 42 patients were treated with dendritic cell-based vaccines, and 29 patients (69.0%) with median age of 61 years (range, 49-84 years) were assessable for tumor responses. The cohort consisted of 18 males and 11 females. As their histological types, 24 patients had adenocarcinomas; 4 patients with squamous cell carcinomas and 1 patient with pleomorphic carcinoma. Among these assessable patients, neither complete response nor partial response was obtained. Seventeen patients had progressive disease as the best response, and 11 patients had stable disease, yielding overall disease control rate of 39.2% (95%CI=20.3-55.6). Median survival time after the vaccines was 10.0 months, and 1-year survival rate was 39.6%. Adverse events related to the vaccines were less frequent. Immunological responses were able to be monitored in five patients, showing that MUC1-specific cytotoxic responses of effector immune cells were achieved in all of those patients, and the population of regulatory T lymphocytes in peripheral blood cells was decreased after the vaccines.
Conclusion:
MUC1-targeted dendritic cell-based vaccine immunotherapy is feasible, and has a potential to control the diseases in patients with refractory NSCLC.
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ORAL18.03 - Discussant for ORAL18.01, ORAL18.02 (ID 3335)
11:07 - 11:17 | Author(s): J. Vansteenkiste
- Abstract
- Presentation
Abstract not provided
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ORAL18.04 - Anti-Angiogenic Therapy in Advanced Non-Small Cell Lung Cancer (NSCLC): A Meta-Analysis of Phase 3 Randomized Trials (ID 937)
11:17 - 11:28 | Author(s): J. Raphael, K.K. Chan, S. Karim, H. Lam, K. Delos Santos, S. Verma
- Abstract
- Presentation
Background:
There is a significant unmet medical need for effective and well-tolerated treatment options for advanced NSCLC patients. Angiogenesis is a fundamental step in tumor growth and progression; its inhibition has become an attractive target as anticancer therapy. We conducted this meta-analysis to evaluate the effectiveness of adding anti-angiogenic therapy (AT) to standard of care (chemotherapy, tyrosine kinase inhibitors (TKIs) or best supportive care) in advanced NSCLC
Methods:
The electronic databases Ovid PubMed, Cochrane Central Register of Controlled Trials, Embase, the websites of European Society of Clinical Oncology, the American Society of Clinical Oncology and the Lung Cancer Association were searched to identify all eligible phase 3, randomized, controlled trials with AT for the treatment of advanced NSCLC. Pooled hazard ratios (HRs) for overall survival (OS) and progression-free survival (PFS), and pooled odds ratio (OR) for overall response rates (RR) were calculated. We divided the population into 2 subgroups based on the dose of Bevacizumab administered: 7.5 mg/kg (group 1) and 15mg/kg (group 2)
Results:
Data of 19098 patients (9867 AT; 9231 controls) from 25 phase III trials were analyzed. Compared with the standard of care alone, the addition of AT did not prolong OS (HR 0.98; 95% [CI] 0.96-1.00; p=0.1 and HR 0.97; 95% [CI] 0.94-1.00; p=0.06 for group 1 and 2 respectively). In an exploratory analysis, the addition of AT did not prolong OS for the adenocarcinoma histology and when it was used in the 1[st] line setting. Furthermore, there was no OS benefit regardless of the type of AT therapy i.e. monoclonal antibodies (Mabs) versus oral TKIs. There was a significant improvement in PFS with the addition of AT (HR 0.85; 95% [CI] 0.79-0.91; p<0.00001 and HR 0.81; 95% [CI] 0.75-0.88; p<0.00001 for group 1 and 2 respectively) and overall RR (OR 1.61; 95% [CI] 1.30-2.01; p<0.0001 and OR 1.72; 95% [CI] 1.39-2.14; p<0.00001 for group1 and 2 respectively).
Conclusion:
This is the 1[st] meta-analysis to our knowledge including all phase 3 trials with AT in NSCLC and showing that the addition of AT to the standard of care in advanced NSCLC had no significant effect on OS and only improved PFS and overall RR. The role of AT in advanced lung cancer is still questionable; strong validated biomarkers are eagerly needed to predict which subgroup might benefit the most from such therapy.
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ORAL18.05 - Early Predictive Value of Perfusion-Computed Tomography (pCT) in Advanced NSCLC Patients Treated with Bevacizumab: IMPACT Trial (ID 2268)
11:28 - 11:39 | Author(s): F. Aya, N. Viñolas, M. Sanchez, M. Benegas, O. Reig, A. Sosa, I. Vollmer, A. Arcoha, A. Martinez, M. Boillos, M. Viladot, A. Prat, N. Reguart
- Abstract
- Presentation
Background:
The use of targeted drugs has implied the development of new imaging techniques able to assess in vivo processes as part of antitumor response. Functional imaging techniques may be more appropriate to study changes in vascularization parameters such as blood flow (BF), blood volume (BV) and permeability (PMB) after treatment with antiangiogenics. Perfusion-computed tomography (pCT) could be a useful technique to predict non-small cell lung cancer (NSCLC) (pts) that most benefit from antiangiogenic therapy by assessing early variations of perfusion parameters.
Methods:
IMPACT (NCT02316327) is an ongoing open-label, single arm phase II/IV study to evaluate the predictive value of early perfusion changes in pts diagnosed with advanced non-squamous (ns)-NSCLC treated with bevacizumab in combination with chemotherapy. Patients receive cisplatin (80 mg/m2 i.v. d1), gemcitabine (1250 mg/m2 i.v. d1 and 8) and bevacizumab (B, 7.5 mg/kg i.v. d1) up to 6 cycles each 21 days. Pts with non-progressive disease are allowed to continue with B maintenance until PD or unacceptable toxicity. pCT assessment is done basal (d-1), at d+7 and d+42. The primary endpoint is to evaluate whether early reductions (d-1 vs d+7) in pCT parameters in terms of BF (mL/100mL/min), BV (mL/100mL) and PMB (mL/100mL/min) may predict response to bevacizumab as compared to Objective Response Rate (ORR) in terms of RECIST after 2 cycles (d+42). All perfusion evaluation parameters during treatment are measured in the same single thoracic target lesion. Planned sample size is 20 pts.
Results:
A total of 12 pts with ns-NSCLC have been recruited and data is available for analysis in 8 pts. Mean age is 62 years, 7 males and 1 female. All pts were diagnosed of adenocarcinoma stage IV (63% stage IVb). All tumor samples were negative for EGFR/ALK and 50% positive for KRAS. Mean cycles of chemotherapy were 5 (range 2-6) and 3 (range 0-12) of B maintenance. Target lesions for perfusion were: lung 3 pts (38%), lymph nodes in 4 pts (50%) and pleura in 1 pt (12%). No differences were found in terms of basal BF, BV and PMB depending on perfusion-target chosen. Four pts (50%) achieved partial response (PR), 3 pts (38%) stable disease (SD) and 1 pt (12%) progressive disease (PD). Mean basal perfusion parameters were: BF 61,5 (34,4 - 109), BV 10,4 (3,7 - 22,2) and PMB 17 (5,5 - 27,9). Mean perfusion changes early assessed by pCT at d+7 were: BF 21,7%, BV -49% and PMB -34,4%, decreasing consistently at day +42 (BF -46,8%, BV -45,5% and PMB -53,9%). Mean early variation (d-1 vs d+7) of BF in pts with SD/PD was +1,7% as compared with -45,3% in pts with PR. Mean variation of BF compared with d+42 (d-1 vs d+42) was also greater in pts with PR (-50%). Similar trends were observed in BV and PMB.
Conclusion:
Early response to B as assessed with p-CT may help to select those pts with NSCLC who most benefit from antiangiogenic therapy. Early changes in perfusion parameters can be identified with B treatment. Recruitment is ongoing.
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ORAL18.06 - Effect of Anti-VEGF Therapy on MDSCs' Population in the Peripheral Blood of Non-Small Cell Lung Cancer (NSCLC) Patients (ID 689)
11:39 - 11:50 | Author(s): F. Koinis, E.K. Vetsika, M. Gioulbasani, D. Aggouraki, A. Koutoulaki, L. Vamvakas, D. Mavroudis, V. Georgoulias, A. Kotsakis
- Abstract
- Presentation
Background:
Bevacizumab is an anti-VEGF monoclonal antibody approved for the treatment of non-squamous NSCLC. It is widely accepted that immunosuppressive mechanisms dominate in patients (pts) with solid tumors, including NSCLC. MDSCs are a heterogeneous population of immature cells of myeloid origin, whose expression is induced by VEGF. We recently identified two monocytic and one granulocytic MDSC subpopulation which are significantly increased and functional in the peripheral blood of NSCLC pts.
Methods:
Peripheral blood immune cells from 46 pts with unresectable NSCLC were analyzed by flow cytometry before the initiation of chemotherapy and after 3 cycles. Changes in the frequencies of the three MDSCs subpopulations were correlated with clinical outcome. Isolated MDSCs were co-cultured with T cells in order to confirm their functionality through estimation of IFN-γ secretion.
Results:
At diagnosis, the CD15(-) monocytic MDSCs’ levels were significantly increased in male pts (p=0.03) and in smokers (p=0.01). Overall, chemotherapy had no effect on the frequency of the distinct MDSC subpopulations. However, after 3 cycles of therapy, levels of all three MDSC subpopulations numerically decreased in responders (n=11) compared to non-responders (n=4). In addition, bevacizumab-based chemotherapy regimens significantly reduced the frequency of the granulocytic MDSC subpopulation when compared to the effect of non-bevacizumab based therapy (p=0.02). Lastly, suppression of IFN-γ secretion in vitro, confirmed the inhibitory effect of isolated MDSCs on T-cell cytotoxic capacity.
Conclusion:
These data indicate that although chemotherapy has no effect on the levels of different immunosuppressive MDSC subpopulations, bevacizumab–based regimens seem to exert an effect on the granulocytic MDSC subpopulation. Additional studies are needed in a larger cohort of pts in order to document its impact in the clinical outcome of NSCLC pts.
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ORAL18.07 - Discussant for ORAL18.04, ORAL18.05, ORAL18.06 (ID 3336)
11:50 - 12:00 | Author(s): P. Lara Jr.
- Abstract
- Presentation
Abstract not provided
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Author of
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MINI 04 - Clinical Care of Lung Cancer (ID 102)
- Event: WCLC 2015
- Type: Mini Oral
- Track: Treatment of Advanced Diseases - NSCLC
- Presentations: 1
- Moderators:L. Gaspar, V. Westeel
- Coordinates: 9/07/2015, 16:45 - 18:15, Mile High Ballroom 2c-3c
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MINI04.10 - Discussant for MINI04.06, MINI04.07, MINI04.08, MINI04.09 (ID 3309)
17:35 - 17:45 | Author(s): K. Reckamp
- Abstract
- Presentation
Abstract not provided
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MINI 16 - EGFR Mutant Lung Cancer 2 (ID 130)
- Event: WCLC 2015
- Type: Mini Oral
- Track: Treatment of Advanced Diseases - NSCLC
- Presentations: 1
- Moderators:G.J. Riely, M.C. Garassino
- Coordinates: 9/08/2015, 16:45 - 18:15, Four Seasons Ballroom F3+F4
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MINI16.03 - Dose Optimization of Rociletinib for EGFR Mutated NSCLC (ID 967)
16:55 - 17:00 | Author(s): K. Reckamp
- Abstract
- Presentation
Background:
Rociletinib (CO-1686) is a novel, oral, irreversible mutant selective tyrosine kinase inhibitor for the treatment of patients with mutant epidermal growth factor receptor (EGFR) non-small cell lung cancer (NSCLC). Rociletinib has demonstrated efficacy against activating mutations (L858R and Del19) and the dominant acquired resistance mutation (T790M), while sparing wild-type EGFR. A maximum tolerated dose was not identified in Phase 1 with 1000 mg BID the highest dose studied. Here we assess the efficacy and safety of the three doses of rociletinib (500 mg BID, 625 mg BID and 750 mg BID) selected for Phase 2 study.
Methods:
TIGER-X (NCT01526928) is a Phase 1/2 open-label, safety, pharmacokinetics and preliminary efficacy study of rociletinib in patients with advanced EGFR mutant NSCLC progressing after ≥1 EGFR tyrosine kinase inhibitor (TKI). Efficacy is assessed using RECIST. Safety is evaluated using standard adverse event (AE) reporting.
Results:
As of April 2015, a total of 231 central T790M positive patients were evaluable for efficacy and 343 for safety (any T790M). All patients were enrolled in the USA (85%), Europe (9%) and Australia (6%). Baseline characteristics were similar in each dose group. The median number of prior therapies was 2. 85% had EGFR TKI as their most recent prior therapy and 10% had a history of diabetes/hyperglycemia. Immature ORRs are 53% (500 mg BID), 52% (625 mg BID) and 43% (750 mg BID), with disease control rates of 89% (500 mg BID), 87% (625 mg BID) and 82% (750 mg BID). The most common ≥grade 3 treatment-related AE was hyperglycemia [16% (500 mg BID), 25% (625 mg BID) and 35% (750 mg BID)] which was managed with oral hypoglycemic agents. Only one patient discontinued the study for hyperglycemia. Grade 3 QTc prolongation was uncommon, occurring in 2% (500 mg BID), 7% (625 mg BID) and 10% (750 mg BID) of patients, and demonstrated a relationship to dose. There were no clinically relevant cutaneous toxicities with 7 cases of grade 1 rash and 4 cases of grade 1 stomatitis (no dose relationship) and no paronychia.
Conclusion:
All 3 Phase 2 doses of rociletinib are active and well tolerated in a Western patient population with advanced NSCLC. The lack of cutaneous toxicities confirms the selectivity of rociletinib for mutant forms of EGFR and is an important contributor to QOL and maintaining dose intensity (Lacouture et al. 2011). Overall, the adverse event frequency appears to be related to dose, but antitumor activity does not, thus the risk/benefit profile may be optimal at the lowest dose studied.
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MINI 28 - Psychological Impact of Lung Cancer and its Treatment (ID 150)
- Event: WCLC 2015
- Type: Mini Oral
- Track: Palliative and Supportive Care
- Presentations: 1
- Moderators:A. Oton
- Coordinates: 9/09/2015, 16:45 - 18:15, 102+104+106
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MINI28.07 - Interdisciplinary Palliative Care for Lung Cancer Patients and Family Caregivers (ID 379)
17:20 - 17:25 | Author(s): K. Reckamp
- Abstract
- Presentation
Background:
Palliative care is focused on supporting the best possible quality of life (QOL) for patients and family caregivers (FCGs) coping with serious and complex illnesses such as lung cancer. Although the accepted definition of palliative care encompasses the entire trajectory of the cancer continuum from diagnosis to the end of life, the majority of published palliative care trials focused primarily on patients with metastatic disease. The purpose of this National Cancer Institute-supported Program Project (P01) was to test the effect of a concurrent, interdisciplinary palliative care intervention in patients with Stage I-IV non-small cell lung cancer (NSCLC) and FCGs in an ambulatory care setting, comparing the usual care and intervention groups.
Methods:
Patients undergoing treatments for NSCLC and their FCGs were enrolled in a prospective, sequential design whereby the usual care group was accrued first followed by the intervention group. Patients and FCGs in the intervention group completed a comprehensive QOL assessment at baseline, and were presented by nurses at weekly interdisciplinary care meetings. They also received four educational sessions that addressed physical, psychological, social, and spiritual well-being needs. Patients and FCGs in the usual care group received disease-focused therapies and procedures and were referred by their treating oncologist to palliative care services as needed per standard of care. Patients’ QOL, symptoms, and psychological distress were assessed at baseline and 12 weeks using validated measures which included the FACT-L, FACIT-Sp-12, LCS, and the Distress Thermometer. FCG outcomes included QOL, psychological distress, perceived burden, and caregiving preparedness, with validated measures that included the COH-QOL-FCG, Distress Thermometer, Caregiver Burden Scale, and Caregiver Skills Preparedness Tool. Outcomes were tested using factorial ANOVAs controlling for baseline scores, with disease stage as a blocking variable and group (usual care versus intervention) as the factor.
Results:
A total of 491 patients (219 = usual care; 272 = intervention) and 354 FCGs (157 = usual care; 197 = intervention) who completed baseline assessments were included in the primary analysis. Patients who received the intervention had significantly better scores for QOL (109.1 vs. 101.4; p<.001), symptoms (25.8 vs. 23.9; p<.001) spiritual well-being (38.1 vs. 36.2; p=.001), lower psychological distress (2.2 vs. 3.3; p<.001), and more advance care planning (44% versus 9%; p<.001) at 12 weeks compared to patients in the usual care group. FCGs in the intervention group had significantly better scores for social well-being (5.84 vs. 6.86; p<.001) and lower psychological distress (4.61 vs. 4.20; p=.010) at 12 weeks compared to FCGs in the usual care group. Survival analysis for stage IV patients using the Kaplan-Meier approach did not achieve statistical significance but showed a 6 month difference in favor of the intervention group. t included the COH-QOL-FCG, Distress Thermometer, Caregiver Burden Scale, and Caregiver Skills Preparedness Tool. Outcomes were tested using factorial ANOVAs controlling for baseline scores, with disease stage as a blocking variable and group (usual care versus intervention) as the factor.
Conclusion:
Interdisciplinary palliative care in the ambulatory care setting resulted in significant improvements in QOL, symptoms, and psychological distress for NSCLC patients and FCGs.
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ORAL 02 - PD1 Axis Immunotherapy 2 (ID 87)
- Event: WCLC 2015
- Type: Oral Session
- Track: Treatment of Advanced Diseases - NSCLC
- Presentations: 1
- Moderators:E.B. Garon, H.J. Ross
- Coordinates: 9/07/2015, 10:45 - 12:15, Four Seasons Ballroom F1+F2
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ORAL02.01 - Phase 3, Randomized Trial (CheckMate 017) of Nivolumab (NIVO) vs Docetaxel in Advanced Squamous (SQ) Cell Non-Small Cell Lung Cancer (NSCLC) (ID 736)
10:45 - 10:56 | Author(s): K. Reckamp
- Abstract
- Presentation
Background:
Treatment options for patients with advanced SQ NSCLC who fail platinum-based doublet chemotherapy (PT-DC) are limited. NIVO, a fully human IgG4 programmed death-1 (PD-1) immune checkpoint inhibitor, demonstrates activity across NSCLC histologies and is approved in the US for treatment of metastatic SQ NSCLC with progression on or after platinum-based chemotherapy. We report results from a randomized, open-label, global phase 3 study (CheckMate 017; NCT01642004) comparing NIVO vs docetaxel in patients with previously treated SQ NSCLC and disease progression during/after one prior PT-DC regimen.
Methods:
Patients (N=272) were randomized 1:1 to receive either NIVO 3 mg/kg every 2 weeks (Q2W; n=135) or docetaxel 75 mg/m[2] Q3W (n=137) until disease progression or discontinuation due to toxicity or other reasons. For NIVO patients, treatment after initial progression was permitted at the investigator’s discretion, per protocol criteria. The primary objective was overall survival (OS). Secondary objectives included investigator-assessed objective response rate (ORR; per RECIST v1.1), progression-free survival (PFS), efficacy by PD-L1 expression (PD-L1 testing not required for enrollment), patient-reported outcomes (PRO), and safety. PRO analyses are presented in a separate abstract.
Results:
Treatment with NIVO led to 41% reduction in risk of death (hazard ratio [HR]=0.59; 95% CI: 0.44, 0.79; P=0.00025) and improved ORR (20% vs 9%; P=0.0083) and PFS (HR=0.62; 95% CI: 0.47, 0.81; P=0.0004) vs docetaxel (Table). Twenty-eight patients were treated with NIVO beyond initial progression, nine of whom demonstrated a non-conventional pattern of benefit (ie, reduction in target lesions with simultaneous appearance of new lesions, initial progression followed by tumor reduction, or no further progression for ≥2 tumor assessments). Across pre-specified cut-points (1%, 5%, and 10%), PD-L1 expression was neither prognostic nor predictive of benefit. OS HRs favored NIVO across most predefined patient subgroups. Grade 3–4 drug-related adverse events (AEs) were reported in 7% (9/131) of NIVO and 55% (71/129) of docetaxel patients. Grade 3–4 drug-related select AEs are shown below (Table). No deaths were related to NIVO vs 3 docetaxel-related deaths. Figure 1
Conclusion:
CheckMate 017 achieved its primary objective, demonstrating clinically superior and statistically significant OS with NIVO vs docetaxel in patients with advanced, previously treated SQ NSCLC. Benefit was seen regardless of PD-L1 status. The safety profile of NIVO 3 mg/kg Q2W is favorable vs docetaxel and consistent with prior studies. AEs were manageable with established guidelines. NIVO represents a new standard of care in this patient population. Updated OS and safety data will be presented.
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P1.01 - Poster Session/ Treatment of Advanced Diseases – NSCLC (ID 206)
- Event: WCLC 2015
- Type: Poster
- Track: Treatment of Advanced Diseases - NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 9/07/2015, 09:30 - 17:00, Exhibit Hall (Hall B+C)
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P1.01-086 - TIGER-3: A Phase 3 Open-Label, Randomized Study of Rociletinib vs Chemotherapy in NSCLC (ID 949)
09:30 - 09:30 | Author(s): K. Reckamp
- Abstract
Background:
Rociletinib (CO-1686) is a novel, oral, irreversible tyrosine kinase inhibitor for the treatment of patients with mutant epidermal growth factor receptor (EGFR) non-small cell lung cancer (NSCLC) that has demonstrated efficacy against the activating mutations (L858R and Del19) and the dominant acquired resistance mutation (T790M), while sparing wild-type EGFR. TIGER-X, a Phase I/II dose-ranging trial, has provided evidence that rociletinib is associated with durable response and is well tolerated in patients with NSCLC and positive T790M status following progression on a TKI.[1 ]Efficacy has also been noted for patients with T790M negative status in TIGER-X.[2] TIGER-3 is designed to investigate single agent rociletinib vs chemotherapy in patients who have failed EGFR therapy and platinum-based doublet chemotherapy, which is a setting of acquired resistance and high unmet need for targeted therapeutic options. TIGER-3 will evaluate patients with T790M positive and negative status based on tumor biopsies and plasma, and biomarkers of response and/or resistance.
Methods:
Patients with histologically or cytologically confirmed metastatic or unresectable locally advanced NSCLC, with radiological progression on the most recent therapy will be enrolled in this phase 3, randomized, open-label study (NCT02322281). Patients must have documented evidence of a tumor with ≥1 EGFR activating mutations excluding exon 20 insertion, and prior treatment with an EGFR TKI and platinum-containing doublet chemotherapy. Patients will be randomized 1:1 to receive rociletinib twice daily (500 mg) or single agent cytotoxic chemotherapy (investigator choice specified before randomization) until disease progression according to RECIST 1.1. Patients will be stratified by presence or absence of brain metastases, ECOG performance status (0 vs 1), and race (Asian vs non-Asian). The primary endpoint is progression-free survival (PFS). Secondary endpoints include safety, objective response rates, duration of response, disease control rate, and overall survival. Kaplan-Meier methodology will assess time to event variables. The stratified log-rank and the hazard ratio will be used for comparing PFS distributions. Serial assessment of safety will be carried out based on standard adverse event reporting. Planned enrolment is 600 patients; enrolment has been open since March 2015. Sequist LV J Clin Oncol. 2014 Soria J-C EORTC-NCI-AACR 2014
Results:
Not applicable
Conclusion:
Not applicable
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P1.11 - Poster Session/ Palliative and Supportive Care (ID 229)
- Event: WCLC 2015
- Type: Poster
- Track: Palliative and Supportive Care
- Presentations: 1
- Moderators:
- Coordinates: 9/07/2015, 09:30 - 17:00, Exhibit Hall (Hall B+C)
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P1.11-004 - Impact of Lung Cancer Surgery on Quality of Life of Family Caregivers (ID 1431)
09:30 - 09:30 | Author(s): K. Reckamp
- Abstract
Background:
Family caregivers (FCGs) of lung cancer patients experience decreased quality of life (QOL) and psychological distress related to their caregiving role. Although there is extensive data about the significant impact of lung cancer surgery on patient QOL, little is known about the impact on FCGs. We describe QOL, psychological distress, and perceived caregiver burden outcomes among FCGs of patients undergoing lung cancer surgery.
Methods:
As part of a National Cancer Institute-supported Program Project (P01) testing the effect of a palliative care intervention in patients with non-small cell lung cancer, patients and their FCGs were sequentially enrolled into a usual care group or an intervention group, which received interdisciplinary care planning as well as a comprehensive assessment and education by an advanced practice nurse. For this subset analysis, we included only those patients who underwent surgery and their FCGs. Outcomes were assessed at baseline (pre-operatively), at 6-7 weeks, and 12 weeks after surgery. FCGs were assessed using the following validated measures: distress thermometer for psychological distress, family version of QOL scale in four domains (physical, psychological, social, and spiritual well being), and Caregiver Burden Scale. Patients were assessed using distress thermometer and FACT-L for QOL domains.
Results:
QOL data were available for 41 pairs of patients and FCGs (10 usual care and 31 intervention). Psychological distress levels were highest for patients (3.8/10) and FCGs (5.1/10) before surgery, then decreased six weeks after surgery for both groups respectively (2.9/10 and 4.2/10). Patients’ distress continued to decrease at 12 weeks (2.2/10, p = .001), but FCGs did not (4.4/10, p = .0.157). Although patients had improvements in all domains between 6 and 12 weeks, FCGs did not experience similar improvements in most domains (Figure 1). Likewise, there was no significant decrease in caregiver objective burden over the 12 weeks (21.1 vs. 21.3, p = 0.942). Patients in the intervention group had improved total QOL at 12 weeks compared to usual care (Total FACT-L 116 vs. 94, p <.001). In contrast, there were no significant differences between the usual care and intervention groups in QOL of FCGs.
Conclusion:
FCGs of lung cancer patients experience significant psychological distress. FCGs continue to have decreased QOL 3 months after lung cancer surgery. The trajectory of QOL for FCGs does not mirror that of patients. FCGs play an important role in patient recovery and greater research is needed to understand how they are impacted by thoracic surgery. Figure 1
