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Sandy Srinivas, MD
Sandy Srinivas, MD
Posted: Friday, January 27, 2023
Results from National Cancer Institute 9984, a randomized phase II trial, demonstrated improvement in radiographic progression–free survival in patients with progressive, metastatic castration-resistant prostate cancer with the combination of a PARP inhibitor and a VEGFR inhibitor over a PARP inhibitor alone. However, the combination of the PARP inhibitor olaparib and the VEGFR inhibitor cediranib was accompanied by a significantly increased rate of grade 3 or 4 toxicities (61% vs. 18%), noted Joseph W. Kim, MD, of Yale Cancer Center, New Haven, Connecticut, and colleagues in the Journal of Clinical Oncology.
The intention-to-treat cohort’s 90 patients were randomly assigned on a 1:1 basis to arm A (cediranib plus olaparib) or arm B (olaparib alone). Median radiographic progression–free survival was 8.5 months and 4.0 months in arms A and B, respectively (P = .0359), representing a 38% reduction in the risk of radiographic disease progression or death with the combination. The combination’s increased toxicities “were manageable with supportive care, [but] treatment interruptions were frequent,” the authors wrote.
Secondary endpoints were radiographic progression–free survival in patients with homologous recombination repair (HRR)-deficient and HRR-proficient disease. The median radiographic progression–free survival was 10.6 versus 3.8 months (hazard ratio = 0.64; 95% confidence interval = 0.272–1.504) among patients with HRR-deficient disease in arms A and B, respectively. Among the patients with BRCA2-mutated disease in arms A and B, respectively, the median radiographic progression–free survival times were 13.8 and 11.3 months.
“[O]ur ongoing whole-exome and transcriptome analyses may help identify [such] a biomarker by examining the genetic landscape beyond HRR genes and evaluating the changes of the gene expression profile with the treatment,” the study investigators predicted. Further, descriptive analyses of radiographic progression–free survival in biomarker subgroups indicated that a deleterious BRCA2 mutation may prove to be the best predictor of olaparib efficacy.
Disclosure: For full disclosures of the study authors, visit ascopubs.org.
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