3010 Phase, randomized trial (CheckMate 057) of nivolumab (NIVO) vs docetaxel (DOC) in advanced non-squamous (non-SQ) non-small cell lung cancer (NSCLC): Subgroup analyses and patient reported outcomes (PROs)

Abstracts

S599

3010 ORAL Phase 3, randomized trial (CheckMate 057) of nivolumab (NIVO) vs docetaxel (DOC) in advanced non-squamous (non-SQ) non-small cell lung cancer (NSCLC): Subgroup analyses and patient reported outcomes (PROs) L. Horn1 , J. Brahmer2 , M. Reck3 , H. Borghaei4 , D.R. Spigel5 , M. Steins6 , N.E. Ready7 , L.Q. Chow8 , E.E. Vokes9 , E. Felip10 , E. Holgado11 , F. Barlesi12 , M.J. Kohlhaufl ¨ 13 , M.A. Burgio14 , J. Fayette15 , S.N. Gettinger16 , C.T. Harbison17 , A. Li18 , F.G. Finckenstein19 , L. Paz-Ares20 . 1 VanderbiltIngram Cancer Center, Department of Medicine, Nashville TN, USA; 2 The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Division of Oncology, Baltimore MD, USA; 3 LungenClinic Grosshansdorf, Airway Research Center North ARCN-German Center for Lung Research DZL, Grosshansdorf, Germany; 4 Fox Chase Cancer Center, Medical Oncology, Philadelphia PA, USA; 5 Sarah Cannon Research Institute/Tennessee Oncology PLLC, Medical Oncology, Nashville TN, USA; 6 ThoraxklinikHeidelberg Ggmbh, Internal Medicine-Oncology, Heidelberg, Germany; 7 Duke University Medical Center, Division of Oncology, Durham NC, USA; 8 University of Washington Division of Oncology, Department of Medicine, Seattle WA, USA; 9 University of Chicago Medicine & Biological Sciences, Department of Medicine, Chicago IL, USA; 10 Hospital Universitari de la Vall d’Hebron, Thoracic Tumor Group, Barcelona, Spain; 11 Hospital De Madrid, Norte Sanchinarro, Servicio de Oncolog´ıa, Madrid, Spain; 12 ˆ Hopital Nord, Multidisciplinary Oncology & Therapeutic Innovations, Marseille, France; 13 Robert-Bosch-Krankenhaus, Pneumonology & Pneumonologic Oncology, Gerlingen, Germany; 14 Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori, Department of Medical ´ ´ ´ Oncology, Meldola, Italy; 15 Centre Leon Berard, Oncologie Medicale, Lyon, France; 16 Yale Comprehensive Cancer Center, Medical Oncology, 17 New Haven CT, USA; Bristol-Myers Squibb, Immuno-Science Metabolic Diseases and Fibrosis, Princeton NJ, USA; 18 Bristol-Myers Squibb, Biostatistics, Princeton NJ, USA; 19 Bristol-Myers Squibb, Oncology Global Clinical Research, Princeton NJ, USA; 20 University Hospital Virgen del ´ Roc´ıo, Servicio de Oncolog´ıa Medica, Sevilla, Spain Background: Treatment options are limited for patients (pts) with advanced non-SQ NSCLC who progress after platinum-based doublet chemotherapy (PT-DC). DOC is approved for second-line treatment of advanced NSCLC; however, no single agent therapy has shown superior survival and improved tolerability vs DOC in this setting. We report results from a randomized, global phase 3 study of NIVO, a fully human IgG4 programmed death-1 (PD-1) immune checkpoint inhibitor antibody, vs DOC in pts with advanced non-SQ NSCLC after failure of PT-DC and tyrosine kinase inhibitor, if eligible. Methods: Pts were randomized to NIVO 3 mg/kg Q2W (n = 292) or DOC 75 mg/m2 Q3W (n = 290) until progression or discontinuation due to toxicity/ other reasons. Primary objective was OS; secondary objectives were investigator-assessed ORR (per RECIST v1.1), PFS, efficacy by PD-L1 expression, PROs, and safety. Results: NIVO improved OS (hazard ratio [HR]=0.73; 96% CI: 0.59, 0.89; P = 0.00155) and ORR (19.2% vs 12.4%; P = 0.0235) vs DOC. HR for PFS was 0.92 (95% CI: 0.77, 1.11; P = 0.393) (Table 1). Grade 3−5 treatmentrelated adverse events (AEs) occurred in 10.5% (30/287) of NIVO and 53.7% (144/268) of DOC pts. Treatment-related serious AEs (SAEs) were less frequent in the NIVO arm. Treatment-related AEs leading to discontinuation (DC) were more common with DOC vs NIVO (Table 2). No deaths were related to NIVO vs 1 DOC-related death. Additional subgroup analyses, including efficacy by tumor PD-L1 expression, and PROs, will be presented. Table 1. Efficacy measures Efficacy measure

NIVO (n = 292)

DOC (n = 290)

Median OS, mo (95% CI) 1-yr OS, % (95% CI) Median response duration, mo (95% CI) Median PFS, mo (95% CI) 1-yr PFS, % (95% CI)

12.2 (9.7, 15.0) 50.5 (44.6, 56.1) 17.1 (8.4, not estimable) 2.3 (2.2, 3.3) 18.5 (14.1, 23.4)

9.4 (8.0, 10.7) 39.0 (33.3, 44.6) 5.6 (4.4, 7.0) 4.2 (3.4, 4.9) 8.1 (5.1, 12.0)

Table 2. Treatment-related adverse events (AE) DOC (n = 268)

NIVO (n = 287)

Treatment-related AEs Treatment-related AEs leading to DC

Any grade, % (n)

Grade 3−5, % (n)

Any grade, % (n)

Grade 3−5, % (n)

69.3 (199) 4.9 (14)

10.5 (30) 3.8 (11)

88.1 (236) 14.9 (40)

53.7 (144) 6.7 (18)

DC, discontinuation.

Conclusions: NIVO significantly improved OS vs DOC in pts with advanced, previously-treated non-SQ NSCLC. The safety profile of NIVO

3 mg/kg Q2W was favorable vs DOC. NIVO demonstrated survival benefit across histologies in two randomized phase 3 trials. Conflict of interest: Ownership. N/A. Advisory boards. L. Horn (Merck and Genetech). M. Reck (Hoffman-La Roche, Eli Lilly, Merck Sharpe & Dohme, Bristol-Myers Squibb, AstraZeneca, Boehringer-Ingelheim, Pfizer, and Novartis). E. Felip (Eli Lilly, Pfizer, Roche, Boehringer-Ingelheim). F. Barlesi (Roche/Genentech, Pfizer, Novartis, Pierre Fabre Medicament, GlaxoSmithKline, Bristol-Myers Squibb, AstraZeneca/MedImmune, Boehringer-Ingelheim, and Eli Lilly). H. Borghaei (Bristol-Myers Squibb, Celgene, Eli Lilly, and Genentech). S. Gettinger (Bristol-Myers Squibb and ARIAD Pharmaceuticals). Board of Directors. N/A. Corporate-sponsored research. J. Brahmer has received grant support from Bristol-Myers Squibb. F. Barlesi’s institution (Roche/Genentech). H. Borghaei’s institution has received research funding from Millennium. S. Gettinger’s institution has received research funding from Bristol-Myers Squibb, ARIAD, Genentech, AstraZeneca, and Bayer. Other substantive relationships. E. Felip has participated in speakers’ bureaus on behalf of Bristol-Myers Squibb, Novartis, and AstraZeneca. F. Barlesi has received honoraria from Genentech/ Roche, Pfizer, Pierre Fabre Medicament, AstraZeneca, GlaxoSmithKline, Daiichi Sankyo, Bristol-Myers Squibb, Boehringer-Ingelheim, Eli Lilly, and Novartis. H. Borghaei has been compensated for travel, expenses and fees by Bristol-Myers Squibb, Celgene, Eli Lilly, and Genentech. D. Spigel has received non-financial support from Bristol-Myers Squibb unconnected to this abstract. N. Ready has received honoraria from Bristol-Myers Squibb and Celgene. E. Vokes reports personal fees from AbbVie, AstraZeneca, and Boehringer-Ingelheim. J. Fayette has a leadership role in Glycotope Company. S. Gettinger has received honoraria from Bristol-Myers Squibb and ARIAD Pharmaceuticals. C. Harbison, C. Dorange, and F. Finckenstein are Bristol-Myers Squibb employees and stockholders. L. Paz-Ares has been a scientific advisor for Eli Lilly, Pfizer, Bristol-Myers Squibb, Roche, AstraZeneca, and Clovis. 3011 ORAL Evaluation of overall health status in patients with advanced squamous non-small cell lung cancer treated with nivolumab or docetaxel in CheckMate 017 M. Reck1 , C. Coon2 , F. Taylor3 , M. DeRosa2 , J.R. Penrod4 , H. Dastani4 , L. Orsini4 , R.J. Gralla5 . 1 LungenClinic Grosshansdorf, Airway Research Center North ARCN-German Center for Lung Research DZL, Grosshansdorf, Germany; 2 Adelphi Values, Healthcare Analytics, Boston MA, USA; 3 Adelphi Values, Endpoint Development & Outcomes Assessment, Boston MA, USA; 4 Bristol-Myers Squibb, HEOR, Princeton NJ, USA; 5 Albert Einstein College of Medicine, Jacobi Medical Center, Bronx NY, USA Background: The CheckMate 017 (NCT01642004) randomized, openlabel, global phase 3 study evaluated efficacy and safety of secondline nivolumab (NIVO) vs docetaxel (DOC) in advanced squamous nonsmall cell lung cancer (NSCLC) patients. Overall survival was significantly superior and duration of treatment (Tx) longer for NIVO versus DOC. Materials and Methods: Patient-reported health status was evaluated using the EuroQOL Group’s EQ-5D preference-based health state utility measure (EQ-5D index) and visual analog scale (EQ-VAS) for overall health status. The EQ-5D index and EQ-VAS are scaled from 0−1 and 0–100, respectively; higher scores indicate better health status. The minimally important difference (MID) has been estimated to be 0.08 for the EQ-5D index and 7 for the EQ-VAS. Assessment was every 4 weeks (wks) for NIVO and every 3 wks for DOC for the first 6 months on Tx and every 6 wks for the rest of the Tx period for both study arms. Following Tx discontinuation, the measures were assessed at 2 follow-up visits. For each measure, the baseline (BL) and the changes from BL at each assessment were summarized by Tx group. Results: EQ-5D completion rates for BL and at least one subsequent assessment were 71.9% (97/135) and 64.2% (88/137) for NIVO and DOC, respectively, and were relatively consistent throughout assessments and by Tx. BL mean [SD] EQ-VAS and EQ-5D index scores were similar for NIVO (63.7 [18.2] and 0.683 [0.208], respectively) and DOC (66.3 [20.5] and 0.663 [0.284], respectively). In the NIVO arm, the EQ-VAS score was statistically higher (P0.05) compared to BL at wks 12, 20 to 36, and 48; of these the differences at wks 24 to 36 and 48 were greater than the MID. On-Tx assessments after wk 54 had fewer than 10 patients. Similarly, the EQ-5D index improved significantly from BL at wks 16 to 30 and wks 42 to 54 (P0.05), with the changes at wks 42 to 54 also larger than the MID. The 2 follow-up assessments after NIVO discontinuation were not significantly different from BL for either the EQ-5D index or the EQ-VAS. In the DOC arm, the EQ-VAS and EQ-5D index scores while on Tx did not differ significantly from BL through wk 18, after which the sample had fewer than 10 patients. At follow-up visit 1, DOC patients’ EQ-VAS showed