Autores: Fizazi, K. (Autor de correspondencia); Retz, M.; Petrylak, D. P.; Goh, J. C.;
Pérez Gracia, José Luis; Lacombe, L.; Zschabitz, S.; Burotto, M.; Mahammedi, H.; Gravis, G.; Bastos, D. A.; McCune, S. L.; Vázquez Limón, J. C. ; Kwan, E. M.; Castellano, D.; Flechon, A.; Saad, F.; Grimm, M. O.; Shaffer, D. R.; Armstrong, A. J.; Bhagavatheeswaran, P.; Amin, N. P.; Unsal-Kacmaz, K.; Wang, X.; Li, J.; Loehr, A.; Pachynski, R. K.
Resumen:
Background CheckMate 9KD (NCT03338790) is a nonrandomized, multicohort, phase 2 trial of nivolumab plus other anticancer treatments for metastatic castration-resistant prostate cancer (mCRPC). We report results from cohorts A1 and A2 of CheckMate 9KD, specifically evaluating nivolumab plus rucaparib. Methods CheckMate 9KD enrolled adult patients with histologically confirmed mCRPC, ongoing androgen deprivation therapy, and an Eastern Cooperative Oncology Group performance status of 0-1. Cohort A1 included patients with postchemotherapy mCRPC (1-2 prior taxane-based regimens) and <= 2 prior novel hormonal therapies (eg, abiraterone, enzalutamide, apalutamide); cohort A2 included patients with chemotherapy-naive mCRPC and prior novel hormonal therapy. Patients received nivolumab 480 mg every 4 weeks plus rucaparib 600 mg two times per day (nivolumab dosing <= 2 years). Coprimary endpoints were objective response rate (ORR) per Prostate Cancer Clinical Trials Working Group 3 and prostate-specific antigen response rate (PSA(50)-RR; >= 50% PSA reduction) in all-treated patients and patients with homologous recombination deficiency (HRD)-positive tumors, determined before enrollment. Secondary endpoints included radiographic progression-free survival (rPFS), overall survival (OS), and safety. Results Outcomes (95% CI) among all-treated, HRD-positive, and BRCA1/2-positive populations for cohort A1 were confirmed ORR: 10.3% (3.9-21.2) (n=58), 17.2% (5.8-35.8) (n=29), and 33.3% (7.5-70.1) (n=9); confirmed PSA(50)-RR: 11.9% (5.9-20.8) (n=84), 18.2% (8.2-32.7) (n=44), and 41.7% (15.2-72.3) (n=12); median rPFS: 4.9 (3.7-5.7) (n=88), 5.8 (3.7-8.4) (n=45), and 5.6 (2.8-15.7) (n=12) months; and median OS: 13.9 (10.4-15.8) (n=88), 15.4 (11.4-18.2) (n=45), and 15.2 (3.0-not estimable) (n=12) months. For cohort A2 they were confirmed ORR: 15.4% (5.9-30.5) (n=39), 25.0% (8.7-49.1) (n=20), and 33.3% (7.5-70.1) (n=9); confirmed PSA(50)-RR: 27.3% (17.0-39.6) (n=66), 41.9 (24.5-60.9) (n=31), and 84.6% (54.6-98.1) (n=13); median rPFS: 8.1 (5.6-10.9) (n=71), 10.9 (6.7-12.0) (n=34), and 10.9 (5.6-12.0) (n=15) months; and median OS: 20.2 (14.1-22.8) (n=71), 22.7 (14.1-not estimable) (n=34), and 20.2 (11.1-not estimable) (n=15) months. In cohorts A1 and A2, respectively, the most common any-grade and grade 3-4 treatment-related adverse events (TRAEs) were nausea (40.9% and 40.8%) and anemia (20.5% and 14.1%). Discontinuation rates due to TRAEs were 27.3% and 23.9%, respectively. Conclusions Nivolumab plus rucaparib is active in patients with HRD-positive postchemotherapy or chemotherapy-naive mCRPC, particularly those harboring BACA1/2 mutations. Safety was as expected, with no new signals identified. Whether the addition of nivolumab incrementally improves outcomes versus rucaparib alone cannot be determined from this trial.
