In the phase 3 PROpel trial, a significant improvement in overall survival is observed for olaparib with abiraterone compared to placebo with abiraterone in patients with mCRPC. The improvement observed was primarily attributable to patients with BRCA mutation. ( Ref: Saad F, et al. Lancet Oncol. Sep 12, 2023)
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In the phase 2 CAPRI trial, patients with recurrent, platinum-sensitive BRCA1/2 mutated or homologous recombination (HR) deficient high-grade serous ovarian cancer (HGSOC) and clinically benefited from PARPi before progression, treated with ceralasertib (ATR inhibitor) and olaparib (PARP inhibitor) showed ORR of 50% (95% confidence interval, 0.15-0.72). ATR inhibition re-sensitizes PARPi-resistant cells to PARP inhibition and has an apparent synergistic effect with PARP inhibition. Grade 3/4 toxicities were 38%: anemia (15%), thrombocytopenia (23%), and neutropenia (8%). The combination was tolerable and showed activity in patients who progressed with PARPi as the penultimate regimen. (Ref: Wethington SL, et al. Clin Cancer Res. August 1, 2023)
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