Abstract 620P
Background
Pembro + docetaxel and prednisone (cohort B) has shown antitumor activity in patients (pts) with mCRPC in the phase I/II KEYNOTE-365 study (NCT02861573). Updated results from cohort B, including time to symptomatic skeletal event, radiographic bone progression, and radiographic soft tissue progression, are reported.
Methods
Pts who received abi or enza for ≤4 wk in the prechemotherapy mCRPC setting and whose disease progressed within 6 mo of screening were eligible. Pts received pembro 200 mg IV + docetaxel 75 mg/m2 IV Q3W and prednisone 5 mg orally twice daily. Primary end points: PSA response rate (decrease ≥50% from baseline), ORR per RECIST v1.1 by blinded independent central review, and safety. Secondary end points: DCR, DOR, rPFS per PCWG-modified RECIST, OS, time to symptomatic skeletal event, radiographic bone progression, and radiographic soft tissue progression.
Results
104 of 105 enrolled pts were treated; 50% had measurable disease. Median (range) time from enrollment to data cutoff was 19.9 (1.4-27.8) mo for all pts and 21.8 (17.9-27.8) mo for pts with ≥27 wk follow-up (n = 72). Confirmed PSA response rate was 28% in 103 pts with baseline PSA assessment. In pts with measurable disease and ≥27 wk follow-up (n = 39), confirmed ORR was 18% (7/39, all PR). For all pts, median rPFS was 8.3 mo (95% CI, 7.6-10.1) and median OS was 20.4 mo (95% CI, 16.9-NR). At 12 mo, rPFS rate was 24.0% and OS rate was 75.8% by Kaplan-Meier. Additional efficacy analyses are displayed in the table. Grade ≥3 treatment-related adverse events (TRAEs) occurred in 40% of pts; 2 pts died of TRAEs (pneumonitis).
Conclusions
Pembro + docetaxel and prednisone continued to show antitumor activity and acceptable safety in pts with abi- or enza-pretreated mCRPC. KEYNOTE-921 phase III study of this combination is ongoing (NCT03834506). Table: 620P
| DCR, n/N (%)a | |
| Measurable disease | 20/39 (51) |
| Nonmeasurable disease | 17/33 (52) |
| Total | 37/72 (51) |
| DOR, median (range), moa | 6.7 (3.4-9.0+)b |
| Response ≥6 mo, n/N (%) | 5/7 (71) |
| Median, mo (95% CI) | |
| Time to confirmed PSA progression | 6.2 (3.7-7.4) |
| Time to symptomatic skeletal-related event | 25.9 (18.3-NR) |
| Event-free survival rate at 12 mo, % | 73.1 |
| Time to radiographic bone progression | 10.3 (9.0-12.2) |
| Event-free survival rate at 12 mo, % | 36.7 |
| Time to radiographic soft tissue progression | 12.4 (9.7-NR) |
| Event-free survival rate at 12 mo, % | 54.9 |
aWith ≥27-wk potential follow-up; b ‘+’ indicates ongoing responder; NR, not reached.
Clinical trial identification
NCT02861573, August 10, 2016.
Editorial acknowledgement
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.
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
E. Romano: Research grant/Funding (institution): Bristol-Myers Squibb, AstraZeneca; Travel/Accommodation/Expenses: AstraZeneca, Merck/MSD, Roche. S.S. Sridhar: Advisory/Consultancy: Merck, Pfizer, Roche, Bristol-Myers Squibb, Janssen, Astellas, AstraZeneca, Bayer. M.P. Kolinsky: Honoraria (self): Janssen, Astellas, Bayer; Advisory/Consultancy: Janssen, Ipsen, Bristol-Myers Squibb, AstraZeneca, Merck; Travel/Accommodation/Expenses: Novartis. G. Gravis: Honoraria (institution): Pfizer, BMS, MSD, AstraZeneca, Astellas, Janssen, Bayer; Advisory/Consultancy: BMS, Pfizer, AstraZeneca, Janssen, Sanofi, Ipsen, Bayer; Travel/Accommodation/Expenses: BMS, Pfizer, AstraZeneca, Janssen, Sanofi, Ipsen, MSD. L. Mourey: Honoraria (self): Sanofi, Astellas, Janssen, Ipsen; Advisory/Consultancy: Advisory/Consultancy Astellas, Sanofi, BMS, Janssen; Travel/Accommodation/Expenses: Astellas, Ipsen, Sanofi, BMS, AstraZeneca, Pfizer, MSD. J.M. Piulats: Advisory/Consultancy: Roche, Novartis, Janssen, Astellas, Bayer, Sanofi Genzyme, MSD, BMS, Merck-Serono, Clovis, AstraZeneca, Beigene, VCN Biotech; Research grant/Funding (self): Roche, Janssen, Astellas, MSD, BMS, Merck-Serono, AstraZeneca, Beigene, VCN Biotech; Travel/Accommodation/Expenses: Roche, Astellas, Janssen. W.R. Berry: Research grant/Funding (self): Merck, Pfizer; Advisory/Consultancy: Pfizer, Genomic Health. H. Gurney: Advisory/Consultancy: BMS, MSD, Pfizer, AstraZeneca, Ipsen, Roche. L.J. Appleman: Research grant/Funding (institution): Acerta, Agensys, Astellas, Aveo, Bayer, Bristol-Myers Squibb, Calithera, Esai, Exelixis, Genentech, Inovio, Novartis, Eli Lilly, Merck, Peloton, Tokai. M. Boegemann: Honoraria (self): Janssen, Astellas, Bayer, Abx, Sanofi, Novartis, Amgen, Pfizer, MSD, BMS, Ipsen, Exelixis, EUSApharm, Eisai, AstraZeneca; Advisory/Consultancy: Janssen, Astellas, Bayer, Abx, Sanofi, Eli Lilly, Novartis, Amgen, Pfizer, MSD, BMS, Ipsen, Exelixis, EUSApharm, Eisai, AstraZeneca, Merck; Research grant/Funding (self): Janssen; Travel/Accommodation/Expenses: Janssen, Bayer, BMS, AstraZeneca. 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, GlaxoSmi. A.M. Joshua: Research grant/Funding (institution): Bristol-Myers Squibb, Janseen Oncology, Merck Sharp & Dohme, Aptevo Therapeutics, Mayne Pharma, Roche/Genentech, Bayer, Macrogenics, Lilly. U. Emmenegger: Honoraria (self): Merck, Astellas; Advisory/Consultancy: Merck, Astellas; Research grant/Funding (institution): Merck, Astellas. H.J. Conter: Full/Part-time employment: Hoffman-La Roche Canada; Advisory/Consultancy: Janssen, Roche; Travel/Accommodation/Expenses: Bayer. B. Laguerre: Honoraria (self): BMS, Astellas, Janssen, AstraZeneca; Travel/Accommodation/Expenses: Pfizer, Astellas, Novartis, Janssen. H. Wu: Full/Part-time employment: Merck; Shareholder/Stockholder/Stock options: Merck. P. Qiu: Full/Part-time employment: Merck; Shareholder/Stockholder/Stock options: Merck. C. Schloss: Full/Part-time employment: Merck; Shareholder/Stockholder/Stock options: Merck. E.Y. Yu: Honoraria (institution): AbbVie, Advanced Accelerator Applications, Amgen, AstraZeneca, Bayer, Clovis, Dendreon, EMD Serono, Incyte, Janssen, Merck, Pharmacyclics, QED, Sanofi Genzyme, Seattle Genetics, Tolmar; Advisory/Consultancy: AbbVie, Advanced Accelerator Applications, Amgen, AstraZeneca, Bayer, Clovis, Dendreon, EMD Serono, Incyte, Janssen, Merck, Pharmacyclics, QED, Sanofi Genzyme, Seattle Genetics, Tolmar; Research grant/Funding (institution): Daiichi-Sankyo, Dendreon, Merck, Pharmacyclics, Seattle Genetics, Taiho. All other authors have declared no conflicts of interest.