Abstract 1139P
Background
Long-term safety of pembrolizumab in metastatic melanoma was analyzed using data from phase 1–3 studies: KEYNOTE-001, KEYNOTE-002, and KEYNOTE-006.
Methods
Safety was assessed in randomized patients who received ≥1 pembrolizumab dose. Lead-time bias was addressed via landmark analyses with patients who were progression-free before day 147.
Results
Adverse events (AEs) were analyzed for 1567 patients. Median follow-up was 42.4 months (range, 24.6-47.8), which represents the largest analysis of the safety of pembrolizumab in advanced melanoma to date. Most treatment-related AEs (TRAEs) were mild/moderate; grade 3/4 TRAEs occurred in 17.7% of patients. Two deaths were considered pembrolizumab-related. Any-grade and grade 3/4 immune-mediated AEs (imAEs) occurred in 23.0% and 6.9% of patients, respectively; imAEs occurring in ≥3.0% of patients were hypothyroidism (9.1%), pneumonitis (3.3%), and hyperthyroidism (3.0%); median time to onset/resolution was 15.9/8.6, 36.0/8.1, and 7.3/6.1 weeks. Most imAEs occurred within 16 weeks of treatment initiation. In the week-21 landmark analysis (n = 291 still on study), patients who did (n = 79) versus did not (n = 384) develop imAEs had similar objective response rates (ORRs) (64.6% vs 63.0%); median time to response (TTR) was 5.6 months for both; median duration of response (DOR) was 20.0 versus 25.3 months; median progression-free survival (PFS) was 17.0 versus 17.7 months; median overall survival (OS) was not reached (NR) versus 43 months (P = 0.1104). Patients who did (n = 17) versus did not (n = 62) receive systemic corticosteroids at week 21 had similar ORRs (70.6% vs 62.9%) and median TTR (6.4 vs 5.6 months) but numerically shorter median PFS (9.9 vs 17.0 months); median DOR was 14.2 months versus NR; median OS was NR for both.
Conclusions
These results further support pembrolizumab use in advanced melanoma, with no new toxicity signals after lengthy follow-up of a large patient population. In landmark analyses, pembrolizumab efficacy was similar regardless of imAE occurrence or systemic corticosteroid use.
Clinical trial identification
KEYNOTE-001, KEYNOTE-002, and KEYNOTE-006: NCT01295827, NCT01704287, and NCT01866319, respectively.
Editorial acknowledgement
Medical writing and/or editorial assistance was provided by Doyel Mitra, PhD, of the ApotheCom pembrolizumab team (Yardley, PA, USA). This assistance was funded by Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.
Legal entity responsible for the study
Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.
Funding
Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.
Disclosure
O. Hamid: Advisory/Consultancy: Merck; Research grant/Funding (institution): Arcus, Aduro, Akeso, Amgen, Array, BMS, Cytomx, Exelixis, Genentech, GSK, Immunocore, Incyte, Iovance, Merck, Moderna, Merck Serono, Nextcure, Novartis, Regeneron, Roche, Seattle Genetics, Torque, and Zelluna. A. Ribas: Honoraria (institution), Advisory/Consultancy: Amgen, Chugai, Genentech-Roche, Novartis, and Merck; Advisory/Consultancy, Shareholder/Stockholder/Stock options: Arcus, Bioncotech, Compugen, Cytomx, Five Prime, FLX-Bio, Merus, Rgenix, PACT Pharma, and Tango Therapeutics. J. Weber: Honoraria (institution), Advisory/Consultancy, Travel/Accommodation/Expenses: Merck, BMS, Genentech, Celldex, Pfizer, and AstraZeneca; Licensing/Royalties, Patent named on a PD-1 biomarker: Biodesix. A.S. Daud: Research grant/Funding (institution): Merck, BMS, Incyte, OncoSec, and Regeneron; Honoraria (self): Regeneron. F.S. Hodi: Advisory/Consultancy, Research grant/Funding (institution): Merck; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Bristol-Myers Squibb, EMD Serono; Advisory/Consultancy: Takeda, Surface, Genentech/Roche, Compass Therapeutics, Verastem, 7 Hills Pharma, Bayer, Aduro, Partners Therapeutics, Sanofi, Pfizer, Rheos, Kairos; Advisory/Consultancy, Licensing/Royalties: Apricity, Torque, Bicara; Advisory/Consultancy: Novartis; Advisory/Consultancy, Licensing/Royalties: Pionyr; Licensing/Royalties: Patent Methods for Treating MICA-Related Disorders (#20100111973); Licensing/Royalties: Patent Angiopoiten-2 Biomarkers Predictive of Anti-immune checkpoint response (#20170248603) pending; Licensing/Royalties: Patent Compositions and Methods for Identification, Assessment, Prevention, and Treatment of Melanoma using PD-L1 Isoforms (#20160340407) pending; Licensing/Royalties: Patent Therapeutic peptides (#20160046716) pending; Licensing/Royalties: Patents pending for Therapeutic Peptides (#20140004112), Therapeutic Peptides (#20170022275), Therapeutic Peptides (#20170008962), Therapeutic Peptides (#9402905), and for methods of using pembrolizumab and trebanaib. J.D. Wolchok: Advisory/Consultancy: Adaptive Biotech; Amgen; Apricity; Ascentage Pharma; Astellas; AstraZeneca; Bayer; Beigene; Bristol-Myers Squibb; Celgene; Chugai; Eli Lilly; F Star; Imvaq; Kyowa Hakko Kirin; Linneaus; MedImmune; Merck; Neon Therapeutics; Ono; Polaris Pharma; Polynoma; P; Research grant/Funding (institution): Bristol-Myers Squibb; AstraZeneca; Shareholder/Stockholder/Stock options: Potenza Therapeutics; Tizona Pharmaceuticals; Adaptive Biotechnologies; Imvaq; Beigene; Trieza; Linneaus. T.C. Mitchell: Honoraria (self): BMS, Aduro, Merck, and Incyte. R.W. Joseph: Advisory/Consultancy: Merck. C. Boutros: Advisory/Consultancy: Bristol-Myers Squibb; Speaker Bureau/Expert testimony: Merck; Travel/Accommodation/Expenses: Amgen, Sandoz. L. Min: Research grant/Funding (institution): BMS. G.V. Long: Advisory/Consultancy: Aduro, Amgen, Array, Bristol-Myers Squibb, Merck Sharp Dohme, Novartis, Pierre-Fabre, Oncosec, and Roche. J. Lin: Full/Part-time employment: Merck. N. Ibrahim: Shareholder/Stockholder/Stock options, Full/Part-time employment: Merck; Shareholder/Stockholder/Stock options: GSK. M. Carlino: Advisory/Consultancy: Merck Sharp & Dohme (MSD), Bristol-Myers Squibb (BMS), Novartis, Roche, Pierre Fabre, Amgen, and Ideaya. C. Robert: Advisory/Consultancy: Roche, Pierre Fabre, Merck, Novartis, Amgen, BMS, Novartis, MSD, and Sanofi. All other authors have declared no conflicts of interest.