417O - Phase 3, randomized trial (CheckMate 057) of nivolumab vs docetaxel in advanced non-squamous (non-SQ) non-small cell lung cancer (NSCLC): subgroup...

Date 19 December 2015
Event ESMO Asia 2015 Congress
Session Thoracic cancers
Topics Anti-Cancer Agents & Biologic Therapy
Non-Small-Cell Lung Cancer, Metastatic
Cancer Immunology and Immunotherapy
Presenter Leora Horn
Citation Annals of Oncology (2015) 26 (suppl_9): 125-147. 10.1093/annonc/mdv532
Authors 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. Kohlhäufl13, M.A. Burgio14, J. Fayette15, S. Gettinger16, C.T. Harbison17, A. Li18, F.G. Finckenstein19, L. Paz-Ares20
  • 1Department Of Medicine, Vanderbilt Ingram Cancer Center, 37232 - Nashville/US
  • 2Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins Hospital, Baltimore/US
  • 3Chefarzt Onkologischer Schwerpunkt, LungenClinic Grosshansdorf, Grosshansdorf/DE
  • 4Medical Oncology, Fox Chase Cancer Center, Philadelphia/US
  • 5Medical Oncology, Sarah Cannon Research Institute-cancer centre, 37203 - Nashville/US
  • 6Internal medicine­-oncology, Thoraxklinik Heidelberg, Heidelberg/DE
  • 7Division of oncology, Duke University Medical Center, Durham/US
  • 8Department Of Medicine, University of Washington Seattle Cancer Care Alliance, 98109 - Seattle/US
  • 9Dept. Of Medicine, The University of Chicago Medical Centre, 60637-1470 - Chicago/US
  • 10Department Of Oncology, Vall d’Hebron University Hospital, Barcelona/ES
  • 11Servicio De Oncologia, Hospital Madrid Norte San Chinarro Centro Integral Oncologico Clara Campal, Madrid/ES
  • 12Multidisciplinary oncology & therapeutic innovations, Hopital Nord, 13915 - Marseille/FR
  • 13Pneumonology & pulmonary Oncology, Klinik Schillerhöhe, 70839 - Gerlingen/DE
  • 14Department of medical oncology, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori, Meldola/IT
  • 15Oncologie médicale, Centre Léon Bérard, Lyon/FR
  • 16Medical oncology, Yale University School of Medicine Medical Oncology, New Haven/US
  • 17Immuno­science metabolic diseases and fibrosis, Bristol-­Myers Squibb, Princeton/US
  • 18Oncology, Bristol‐Myers Squibb, Princeton/US
  • 19Oncology global clinical research, Bristol­-Myers Squibb, Princeton/US
  • 20Servicio de oncología médica, Hospital Universitario Virgen del Rocio, Sevilla/ES

Abstract

Aim/Background

We report results from a phase 3 study of nivolumab vs docetaxel in patients with advanced non-SQ NSCLC after failure of platinum-doublet chemotherapy and a tyrosine kinase inhibitor, if eligible.

Methods

Patients were randomized to nivolumab 3 mg/kg every 2 weeks (Q2W) (n = 292) or docetaxel 75 mg/m2 Q3W (n = 290) until progression or discontinuation due to toxicity/other reasons. Primary objective was overall survival (OS) and secondary objectives include investigator-assessed overall response rate (ORR) (per RECIST [Response Evaluation Criteria in Solid Tumors] v1.1), progression-free survival (PFS), efficacy by programmed death ligand-1 (PD-L1) expression, PROs, and safety.

Results

Nivolumab improved OS (hazard ratio [HR] = 0.73; 96% CI: 0.59, 0.89; P = 0.00155) and ORR (19.2% vs 12.4%; P = 0.0246) vs docetaxel. HR for PFS was 0.92 (95% CI: 0.77, 1.11; P = 0.393). Median OS was 12.2 months (mo) (95% CI: 9.7, 15.0) vs 9.4 mo (95% CI: 8.0, 10.7) for nivolumab and docetaxel, respectively, and 1-year OS was 50.5% (95% CI: 44.6, 56.1) vs 39.0% (95% CI: 33.3, 44.6). Median PFS was 2.3 mo (95% CI: 2.2, 3.3) vs 4.2 mo (95% CI: 3.4, 4.9) and 1-year PFS was 18.5% (95% CI: 14.1, 23.4) vs 8.1% (95% CI: 5.1, 12.0). Nivolumab improved median response duration (17.1 mo [95% CI: 8.4, not estimable] vs 5.6 mo [95% CI: 4.4, 7.0]). Grade 3–5 treatment-related adverse events (TRAEs) occurred in fewer nivolumab-treated patients (Table). TRAEs leading to discontinuation were more common with docetaxel. Serious treatment-related AEs were less frequent in the nivolumab arm. PROs and efficacy by tumor PD-L1 expression will also be presented.

Nivolumab (n = 287) Nivolumab (n = 287) Docetaxel (n = 268) Docetaxel (n = 268)
Any grade % (n) Grade 3–5 % (n) Any grade % (n) Grade 3–5 % (n)
TRAEs 69.3 (199) 10.5 (30) 88.1 (236) 53.7 (144)
TRAEs leading to discontinuation 4.9 (14) 3.8 (11) 14.9 (40) 6.7 (18)

Conclusions

Nivolumab significantly improved OS vs docetaxel in patients with advanced, previously treated, non-SQ NSCLC. The safety profile of nivolumab 3 mg/kg Q2W was favorable vs docetaxel.

Clinical trial identification

NCT01673867

Disclosure

L. Horn: non-financial support from StemScientific during the study; personal fees from Bristol Myers Squibb, Merck; other from Bayer, Xcovery; grants from Astellas; personal fees from Clovis, Helix bio, Genentech, outside the submitted work. J. Brahmer: non-financial support from StemScientific, during the conduct of the study; grants from Bristol Myers Squibb, outside the submitted work. M. Reck: Advisory board: Hoffman-LaRoche, Lilly, MSD, BMS, AstraZeneca, Boehringer-Ingelheim, Pfizer, Novartis; tobacco-related remuneration to disclose. H. Borghaei: non-financial support from Stem Scientific during the study; grants from Millennium, personal fees and other from Eli Lilly, Bristol-Myers Squibb, Celgene, Genentech, outside the submitted work. D.R. Spigel: non-financial support from StemScientific during the conduct of the study; non-financial support from Bristol Myers Squibb outside the submitted work. N.E. Ready: non-financial support from StemScientific during the conduct of the study; personal fees from Bristol-Myers Squib, personal fees from Celgene, personal fees from Onyx, outside the submitted work. L.Q. Chow: Non-financial support from Stem Scientific during the study; personal fees-Astellas, BMS; pers. fees, other-Novartis, Merck; grants-Lilly/Imclone, OSI Pharma, BMS, Genentech, VentiRx, Pfizer, GSK, Merck, AZ/MedImmune, Novartis, outside submitted work. E.E. Vokes: non-financial support from StemScientific during the study; personal fees from AbbVie, AstraZeneca, Boehringer Ingelheim, Celgene, Clovis, Eli Lilly, GeneCentric, Genentech, Merck, Synta, Transgene, VentiRx outside the submitted work. E. Felip: Non-financial support from StemScientific during the study; personal fees from Eli Lilly, Pfizer, Roche, Boehringer Ingelheim, Astra Zeneca, BMS, MSD, Novartis, outside the submitted work. E. Holgado: Travel, Accomodations, Expenses provided by Merck Serono and Roche. F. Barlesi: personal fees from BMS during the conduct of the study; grants and personal fees from Roche; personal fees from Lilly, Novartis, Pfizer, Astra-Zeneca, Boehringer Ingelheim outside the submitted work. M. Kohlhäufl: non-financial support from StemScientific, during the conduct of the study. S.N. Gettinger: non-financial support from Stem Scientific during the study; grants from BMS, AstraZeneca, ARIAD, Genentech, Bayer; personal fees from BMS, ARIAD; personal fees from BMS, ARIAD, outside the submitted work. C.T. Harbison: non-financial support from StemScientific, other from Bristol-Myers Squibb; other from Bristol-Myers Squibb outside the submitted work. A. Li: Dr. employee of BMS and has stock ownership in BMS. F.G. Finckenstein: non-financial support from StemScientific, during the conduct of the study; personal fees and other from Bristol Myers Squibb, outside the submitted work. L. Paz-Ares: personal fees from Bristol-Myers Squibb, outside the submitted work. All other authors have declared no conflicts of interest.