Title | Randomized Trial of Olaparib With or Without Cediranib for Metastatic Castration-Resistant Prostate Cancer: The Results From National Cancer Institute 9984. |
Publication Type | Journal Article |
Year of Publication | 2023 |
Authors | Kim JW, McKay RR, Radke MR, Zhao S, Taplin M-E, Davis NB, Monk P, Appleman LJ, Lara PN, Vaishampayan UN, Zhang J, Paul AK, Bubley G, Van Allen EM, Unlu S, Huang Y, Loda M, Shapiro GI, Glazer PM, LoRusso PM, S Ivy P, Shyr Y, Swisher EM, Petrylak DP |
Journal | J Clin Oncol |
Volume | 41 |
Issue | 4 |
Pagination | 871-880 |
Date Published | 2023 Feb 01 |
ISSN | 1527-7755 |
Keywords | Antineoplastic Combined Chemotherapy Protocols, Humans, Male, National Cancer Institute (U.S.), Phthalazines, Prostatic Neoplasms, Castration-Resistant, United States, Vascular Endothelial Growth Factor A |
Abstract | PURPOSE: Cediranib, a pan-vascular endothelial growth factor receptor inhibitor, suppresses expression of homologous recombination repair (HRR) genes and increases sensitivity to poly-(ADP-ribose) polymerase inhibition in preclinical models. We investigated whether cediranib combined with olaparib improves the clinical outcomes of patients with prostate cancer. METHODS: Patients with progressive metastatic castration-resistant prostate cancer (mCRPC) were randomly assigned 1:1 to arm A: cediranib 30 mg once daily plus olaparib 200 mg twice daily or arm B: olaparib 300 mg twice daily alone. The primary end point was radiographic progression-free survival (rPFS) in the intention-to-treat patients. The secondary end points were rPFS in patients with HRR-deficient and HRR-proficient mCRPC. RESULTS: In the intention-to-treat set of 90 patients, median rPFS was 8.5 (95% CI, 5.4 to 12.0) and 4.0 (95% CI, 3.2 to 8.5) months in arms A and B, respectively. Cediranib/olaparib significantly improved rPFS versus olaparib alone (hazard ratio [HR], 0.617; 95% CI, 0.392 to 0.969; P = .0359). Descriptive analyses showed a median rPFS of 10.6 (95% CI, 5.9 to not assessed [NA]) and 3.8 (95% CI, 2.33 to NA) months (HR, 0.64; 95% CI, 0.272 to 1.504) among patients with HRR-deficient mCRPC, and 13.8 (95% CI, 3.3 to NA) and 11.3 (95% CI, 3.8 to NA) months (HR, 0.98; 95% CI, 0.321 to 2.988) among patients with BRCA2-mutated mCRPC in arms A and B, respectively. The incidence of grades 3-4 adverse events was 61% and 18% in arms A and B, respectively. CONCLUSION: Cediranib combined with olaparib improved rPFS compared with olaparib alone in men with mCRPC. This combination was associated with an increased incidence of grades 3-4 adverse events. BRCA2-mutated subgroups treated with olaparib with or without cediranib were associated with a numerically longer median rPFS. |
DOI | 10.1200/JCO.21.02947 |
Alternate Journal | J Clin Oncol |
PubMed ID | 36256912 |
PubMed Central ID | PMC9901975 |
Grant List | P30 CA093373 / CA / NCI NIH HHS / United States R01 ES005775 / ES / NIEHS NIH HHS / United States UM1 CA186690 / CA / NCI NIH HHS / United States UL1 TR001863 / TR / NCATS NIH HHS / United States UM1 CA186709 / CA / NCI NIH HHS / United States UM1 CA186712 / CA / NCI NIH HHS / United States R35 CA197574 / CA / NCI NIH HHS / United States UM1 CA186717 / CA / NCI NIH HHS / United States |
Related Faculty:
Massimo Loda, M.D.