Pembrolizumab monotherapy has shown antitumor activity and acceptable safety in patients with mCRPC previously treated with a next-generation hormonal agent (NHA) and docetaxel.
The KEYNOTE-199 phase II study (NCT02787005) enrolled patients with RECIST-measurable PD-L1+ disease, RECIST-measurable PD-L1− disease, and bone-predominant disease irrespective of PD-L1 status in C1, C2, and C3, respectively. Patients had prior treatment with ≥1 NHA and 1 or 2 chemotherapies, including docetaxel, and received pembrolizumab 200 mg Q3W for 35 cycles or until progression/toxicity. The primary end point was ORR per RECIST v1.1 by blinded independent central review. Key secondary end points were time to PSA progression, DCR, PSA response rate, rPFS, OS, DOR, and safety.
In total, 258 patients were treated (C1: 133; C2: 67; C3: 58), of whom 6 completed therapy (C1: 4; C3: 2). The median (range) time from enrollment to data cutoff was 31.3 mo (26.7-34.7), 30.6 mo (28.0-34.1), and 32.6 mo (27.4-34.4) in C1, C2, and C3, respectively. In patients with measurable disease, ORR (95% CI) was 6% (2.6-11.5) in C1 and 3% (0.4-10.4) in C2, and 6 of 10 responders experienced DOR ≥18 mo (Table). Median time to PSA progression was 4 mo regardless of cohort (Table). Grade ≥3 treatment-related AEs (TRAEs) occurred in 16%, 15%, and 17% of patients in C1, C2, and C3, respectively (1 death in each cohort from a TRAE [C1: sepsis; C2: unknown; C3: immune-related pneumonitis]). Efficacy outcomes a≥50% decrease from baseline.
Cohort 1 Measurable, PD-L1+ n = 133 Cohort 2 Measurable, PD-L1− n = 67 Cohort 3 Bone Predominant n = 58 ORR per RECIST v1.1 per BICR, measurable disease, n/N (%) 8/133 (6) 2/67 (3) – CR, n/N (%) 3/133 (2) 0 – PR, n/N (%) 5/133 (4) 2/67 (3) – DCR (CR + PR + SD or non-CR/non-PD ≥6 mo), n/N (%) 14/133 (11) 4/67 (6) 12/58 (21) PSA response rate,a pts w/baseline PSA, n/N (%) 8/124 (6) 5/61 (8) 1/58 (2) Median time to PSA progression, mo (95% CI) 4 (4-4) 4 (4-6) 4 (4-4) Median rPFS per PCWG3-modified RECIST, mo (95% CI) 2 (2-2) 2 (2-3) 4 (2-4) Median OS, mo (95% CI) 10 (6-12) 8 (6-10) 14 (11-18) OS at 24 mo, % 22 16 21
In 3 cohorts of docetaxel and NHA-pretreated patients with RECIST-measurable or bone-predominant mCRPC, pembrolizumab monotherapy led to promising antitumor activity and disease control and was well tolerated. There was durable antitumor activity and disease control, with survival up to 24 mo.
NCT02787005, June 1, 2016.
Medical writing and/or editorial assistance was provided by Matthew Grzywacz, 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.
Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.
Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.
J.C.H. Goh: Shareholder/Stockholder/Stock options: Immutep Ltd.; Honoraria (self): MSD; Advisory/Consultancy: AstraZeneca, Tesaro, BMS; Speaker Bureau/Expert testimony: Ipsen; Travel/Accommodation/Expenses: AstraZeneca, Astellas. J.M. Piulats: Advisory/Consultancy: Roche, Novartis, Jansen, Astellas, Bayer, Sanofy-Genzyme, MSD, BMS, Merk-Serono, Clovis, AstraZeneca, Beigene, VCN Biotech; Research grant/Funding (self): Roche, Jansen, Astellas, MSD, BMS, Merk-Serono, AstraZeneca, Beigene, VCN Biotech; Travel/Accommodation/Expenses: Roche, Astellas, Jansen. M. Gross-Goupil: Honoraria (self): Ipsen, Janssen, Astellas; Advisory/Consultancy: Astellas, Janssen, Ipsen, MSD; Research grant/Funding (self): MSD, BMS, Janssen, AstraZeneca, Pfizer, Roche; Travel/Accommodation/Expenses: Amgen, MSD, Roche, Pfizer, Sanofi. U.N. Vaishampayan: Advisory/Consultancy, Research grant/Funding (institution): Merck & Co., Inc. R. de Wit: Advisory/Consultancy, Speaker Bureau/Expert testimony: Merck, Sanofi, Roche, Janssen, Clovis. T.V. Alanko: Honoraria (institution): Eli Lilly, Roche; Advisory/Consultancy: Bayer, BMS, Celgene, Eli Lilly, MSD, Nordic Drugs, Roche, Shire; Speaker Bureau/Expert testimony: Bayer, Servier; Travel/Accommodation/Expenses: BMS, Celgene, MSD, Roche, Shire. S. Fukasawa: Speaker Bureau/Expert testimony: Pfizer, Bristol-Myers Squibb, Ono Pharmaceutical, Janssen Pharmaceutical. S. Feyerabend: Advisory/Consultancy: AstraZeneca, Bayer; Travel/Accommodation/Expenses: Janssen. R. Berger: Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: MSD, BMS, AZ. H. Wu: Shareholder/Stockholder/Stock options, Full/Part-time employment: Merck & Co., Inc. J. Kim: Shareholder/Stockholder/Stock options, Full/Part-time employment: Merck & Co., Inc. C. Schloss: Shareholder/Stockholder/Stock options, Full/Part-time employment: Merck & Co., Inc. J.S. de Bono: Advisory/Consultancy: AstraZeneca, Sanofi, Astellas Pharma, Pfizer, Genentech/Roche, Janssen Oncology, Menarini Silicon Biosystems, Daiichi Sankyo, Sierra Oncology, Bayer, Merck Sharp & Dohme, Merck Serono, Boehringer Ingelheim, Celgene, Taiho Pharmaceuticals, Genmab, SlasoSmi; Research grant/Funding (institution): AstraZeneca, Genentech, Sanofi, Taiho Pharmaceuticals, Daiichi Sankyo, Merck Serono, Astex Pharmaceuticals, Merck Sharp & Dohme, Orion Pharma, GlaxoSmithKline, Cellcentric, Celgene, Sierra Oncology, Bayer, MedImmune, Medication, Terumo, Astellas Pharma, G. E.S. Antonarakis: Research grant/Funding (self): Janssen, Sanofi, Dendreon, AstraZeneca Clovis, Merck, JohnsonJohnson, Genentech, Novartis, Bristol-Myers Squibb, Eli Lilly, Tokai, Celgene; Advisory/Consultancy: Janssen, Astellas, Sanofi, Dendreon, Medivation, ESSA, AstraZeneca, Clovis, Merck, Eli Lilly, Amgen, Bayer, GlaxoSmithKline; Licensing/Royalties: Qiagen. All other authors have declared no conflicts of interest.