Randomized Trial of Olaparib With or Without Cediranib for Metastatic Castration-Resistant Prostate Cancer: The Results From National Cancer Institute 9984

Joseph W. Kim, Rana R. McKay, Marc R. Radke, Shilin Zhao, Mary Ellen Taplin, Nancy B. Davis, Paul Monk, Leonard J. Appleman, Primo N. Lara, Ulka N. Vaishampayan, Jingsong Zhang, Asit K. Paul, Glenn Bubley, Eliezer M. Van Allen, Serhan Unlu, Ying Huang, Massimo Loda, Geoffrey I. Shapiro, Peter M. Glazer, Patricia M. LorussoS. Percy Ivy, Yu Shyr, Elizabeth M. Swisher, Daniel P. Petrylak

Research output: Contribution to journalArticlepeer-review

18 Citations (Scopus)

Abstract

PURPOSECediranib, 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.METHODSPatients 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.RESULTSIn 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.CONCLUSIONCediranib 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.

Original languageEnglish
Pages (from-to)871-880
Number of pages10
JournalJournal of Clinical Oncology
Volume41
Issue number4
DOIs
Publication statusPublished - 2023 Feb 1

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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