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.
