1. Pembrolizumab plus Olaparib in Patients with Metastatic Castration-resistant Prostate Cancer: Long-term Results from the Phase 1b/2 KEYNOTE-365 Cohort A Study
- Author
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Evan Y. Yu, Josep M. Piulats, Gwenaelle Gravis, Peter C.C. Fong, Tilman Todenhöfer, Brigitte Laguerre, Jose A. Arranz, Stephane Oudard, Christophe Massard, Julia Heinzelbecker, Luke T. Nordquist, Joan Carles, Michael P. Kolinsky, Marinela Augustin, Howard Gurney, Ali Tafreshi, Xin Tong Li, Ping Qiu, Christian H. Poehlein, Charles Schloss, Johann S. de Bono, Institut Català de la Salut, [Yu EY] University of Washington and Fred Hutchinson Cancer Center, Seattle, WA, USA. [Piulats JM] Catalan Institute of Oncology, Barcelona, Spain. [Gravis G] Institut Paoli Calmettes, Marseille, France. [Fong PCC] Auckland City Hospital, Auckland, New Zealand. University of Auckland, Auckland, New Zealand. [Todenhöfer T] Studienpraxis Urologie, Nürtingen, Germany. [Laguerre B] Centre Eugène Marquis, Rennes, France. [Carles J] Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain, and Vall d'Hebron Barcelona Hospital Campus
- Subjects
Male ,Anticossos monoclonals - Ús terapèutic ,Urology ,Medicaments antineoplàstics - Ús terapèutic ,Otros calificadores::Otros calificadores::/farmacoterapia [Otros calificadores] ,acciones y usos químicos::acciones farmacológicas::usos terapéuticos::antineoplásicos [COMPUESTOS QUÍMICOS Y DROGAS] ,Docetaxel ,Prostate-Specific Antigen ,Pròstata - Càncer - Tractament ,Other subheadings::Other subheadings::/drug therapy [Other subheadings] ,Neoplasms::Neoplasms by Site::Urogenital Neoplasms::Genital Neoplasms, Male::Prostatic Neoplasms::Prostatic Neoplasms, Castration-Resistant [DISEASES] ,Progression-Free Survival ,Prostatic Neoplasms, Castration-Resistant ,neoplasias::neoplasias por localización::neoplasias urogenitales::neoplasias de los genitales masculinos::neoplasias de la próstata::neoplasias prostáticas resistentes a la castración [ENFERMEDADES] ,Humans ,Chemical Actions and Uses::Pharmacologic Actions::Therapeutic Uses::Antineoplastic Agents [CHEMICALS AND DRUGS] ,Amino Acids, Peptides, and Proteins::Proteins::Blood Proteins::Immunoproteins::Immunoglobulins::Antibodies::Antibodies, Monoclonal [CHEMICALS AND DRUGS] ,Response Evaluation Criteria in Solid Tumors ,aminoácidos, péptidos y proteínas::proteínas::proteínas sanguíneas::inmunoproteínas::inmunoglobulinas::anticuerpos::anticuerpos monoclonales [COMPUESTOS QUÍMICOS Y DROGAS] ,Aged - Abstract
Metastatic castration-resistant prostate cancer; Olaparib; Pembrolizumab Cáncer de próstata metastásico resistente a la castración; Olaparib; Pembrolizumab Càncer de pròstata metastàtic resistent a la castració; Olaparib; Pembrolizumab Background Pembrolizumab and olaparib have shown single-agent activity in patients with previously treated metastatic castration-resistant prostate cancer (mCRPC). Objective To evaluate the efficacy and safety of pembrolizumab plus olaparib in mCRPC. Design, setting, and participants Cohort A of the phase 1b/2 KEYNOTE-365 study enrolled patients with molecularly unselected, docetaxel-pretreated mCRPC whose disease progressed within 6 mo of screening. Intervention Pembrolizumab 200 mg intravenously every 3 wk plus olaparib 400-mg capsule or 300-mg tablet orally twice daily. Outcome measurements and statistical analysis The primary endpoints were safety, confirmed prostate-specific antigen (PSA) response rate, and objective response rate (ORR) as per Response Evaluation Criteria in Solid Tumors (RECIST), version 1.1, by blinded independent central review. The secondary endpoints included radiographic progression-free survival (rPFS) and overall survival (OS). Results and limitations Of 104 enrolled patients, 102 were treated. The median age was 70 yr (interquartile range [IQR], 65–76), and 59 patients (58%) had measurable disease as per RECIST v1.1. The median time from the first dose to database cutoff was 24 mo (IQR, 22–47). The confirmed PSA response rate was 15%. The confirmed ORR was 8.5% (five partial responses) for patients with measurable disease. The median rPFS was 4.5 mo (95% confidence interval [CI], 4.0–6.5) and median OS was 14 mo (95% CI, 10.4–18.2). Clinical activity was consistent across the programmed death ligand 1 (PD-L1)-positive and homologous recombination repair mutation subgroups. Treatment-related adverse events (TRAEs) occurred in 93 patients (91%). Grade 3–5 TRAEs occurred in 49 patients (48%). Six deaths (5.9%) were due to adverse events; two (myocardial infarction and unknown cause) were attributed to treatment. Limitations of the study include the single-arm design. Conclusions Pembrolizumab plus olaparib had a safety profile consistent with the profiles of the individual agents and demonstrated antitumor activity in previously treated patients with molecularly unselected, docetaxel-pretreated mCRPC.
- Published
- 2023