Pembrolizumab (pembro) plus abiraterone acetate (abi) and prednisone (p) in patients with chemotherapy-naive metastatic castration-resistant prostate cancer (mCRPC): Results from KEYNOTE-365 cohort D

Autor: Cristiano Ferrario, Josep M. Piulats, Mark David Linch, Michael Stoeckle, Brigitte Laguerre, José A. Arranz, Tilman Todenhöfer, Peter C.C. Fong, William R. Berry, Urban Emmenegger, Loic Mourey, Nataliya Mar, Leonard Joseph Appleman, Anthony M. Joshua, Henry Jacob Conter, Xin Tong Li, Charles Schloss, Christian Heinrich Poehlein, Johann S. De Bono, Evan Y. Yu
Rok vydání: 2022
Předmět:
Zdroj: Journal of Clinical Oncology. 40:118-118
ISSN: 1527-7755
0732-183X
Popis: 118 Background: Abi + p is a standard of care for mCRPC. Cohort D of the phase 1b/2 KEYNOTE-365 study (NCT02861573) was used to evaluate safety and efficacy of the PD-1 inhibitor pembro + abi and p in patients (pts) who had not received chemotherapy for mCRPC. Methods: Chemotherapy-naive pts who had not previously used next-generation hormonal agents (NHAs) for mCRPC or were intolerant to enzalutamide or for whom enzalutamide was ineffective for mCRPC, whose disease progressed ≤6 months before screening, and who had ECOG PS score 0/1 were eligible. Enrolled pts received pembro 200 mg IV Q3W + abi 1000 mg PO QD and p 5 mg PO BID. Primary end points were PSA response rate (PSA decrease ≥50% from baseline), confirmed ORR per RECIST v1.1 by blinded independent central review, and safety. Secondary end points included rPFS per PCWG3-modified RECIST v1.1, DCR (CR + PR + SD or non-CR/non-PD ≥6 mo), DOR, OS, time to symptomatic skeletal-related event, radiographic bone progression, and radiographic soft tissue progression. Results: Of 103 treated pts, 35.9% had RECIST-measurable disease and 26.2% had previously received enzalutamide. Median (range) time from enrollment to data cutoff was 17.6 (9.7-27.0) months. Confirmed PSA response rate in all 103 pts was 56.3%. Overall, 78.6% of pts had a reduction in PSA level from baseline (confirmed and unconfirmed). For 37 pts with RECIST-measurable disease, ORR was 16.2% (1 CR; 5 PRs) overall, 7.7% for those who previously received enzalutamide (n = 13) and 21.7% for those who had not previously received NHAs (n = 23). Two pts with RECIST-nonmeasurable disease had a CR. DOR was not reached (NR; range, 2.1+ to 19.4+ mo); 4 pts had a response ≥12 months. DCR was 44.7% overall, 11.1% in pts who previously received enzalutamide (n = 27), and 57.3% in pts who had not previously used NHAs (n = 75). Additional analyses are listed in the table. Treatment-related AEs (TRAEs) were experienced by 90.3% of pts; 36.9% experienced grade 3-5 TRAEs. Overall, 18.4% of pts had a grade 3/4 ALT laboratory elevation and 12.6% had a grade 3/4 AST elevation. Five pts died of AEs; 1 was treatment-related (myasthenic syndrome). Conclusions: Pembro + abi and p showed antitumor activity in chemotherapy-naive pts with mCRPC. Safety was generally consistent with individual profiles of each agent, although there was an increased incidence of grade 3/4 ALT/AST laboratory elevations than reported for the individual treatments. Clinical trial information: NCT02861573. [Table: see text]
Databáze: OpenAIRE
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