{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Kim JW"],"funding":["NCATS NIH HHS","NIEHS NIH HHS","NCI NIH HHS"],"pagination":["871-880"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC9901975"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["41(4)"],"pubmed_abstract":["<h4>Purpose</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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; <i>P</i> = .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 <i>BRCA2</i>-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.<h4>Conclusion</h4>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. <i>BRCA2</i>-mutated subgroups treated with olaparib with or without cediranib were associated with a numerically longer median rPFS."],"journal":["Journal of clinical oncology : official journal of the American Society of Clinical Oncology"],"pubmed_title":["Randomized Trial of Olaparib With or Without Cediranib for Metastatic Castration-Resistant Prostate Cancer: The Results From National Cancer Institute 9984."],"pmcid":["PMC9901975"],"funding_grant_id":["UM1 CA186717","UM1 CA186690","R35 CA197574","R01 ES005775","P30 CA093373","UL1 TR001863","UM1 CA186712"],"pubmed_authors":["Swisher EM","Petrylak DP","Radke MR","Zhang J","Lara PN","Kim JW","LoRusso PM","Vaishampayan UN","Shapiro GI","Taplin ME","Shyr Y","Zhao S","Huang Y","Davis NB","Loda M","Van Allen EM","Paul AK","Unlu S","Ivy SP","Monk P","Bubley G","Glazer PM","McKay RR","Appleman LJ"],"additional_accession":[]},"is_claimable":false,"name":"Randomized Trial of Olaparib With or Without Cediranib for Metastatic Castration-Resistant Prostate Cancer: The Results From National Cancer Institute 9984.","description":"<h4>Purpose</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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; <i>P</i> = .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 <i>BRCA2</i>-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.<h4>Conclusion</h4>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. <i>BRCA2</i>-mutated subgroups treated with olaparib with or without cediranib were associated with a numerically longer median rPFS.","dates":{"release":"2023-01-01T00:00:00Z","publication":"2023 Feb","modification":"2025-04-04T11:50:37.641Z","creation":"2025-04-04T11:50:37.641Z"},"accession":"S-EPMC9901975","cross_references":{"pubmed":["36256912"],"doi":["10.1200/JCO.21.02947"]}}