Olaparib with or without cediranib for metastatic castration-resistant prostate cancer

In preclinical models the pan-VEGFR inhibitor cediranib suppresses expression of HRR genes and increases sensitivity to PARP inhibition. The multicenter 9984 study of the National Cancer Institute evaluated addition of cediranib to the PARP inhibitor olaparib for metastatic castration-resistant prostate cancer. Addition of cediranib to olaparib improved radiographic progression-free survival among all randomized patients (panel A), did not improve overall survival (panel B), did improve rPFS in the HRR-deficient subgroup (panel C), and did not improve rPFS in the HRR-proficient subgroup (panel D), and was associated with higher incidence of grade 3 and 4 events (61% versus 18%). Panel E shows that patients with BRCA2-mutation had numerically longer rPFS in both arms compared with the ITT population.