ESMO 2019: Activity of Cediranib Plus Olaparib in Platinum-Resistant Ovarian Cancer
Posted: Monday, October 28, 2019
Given the promising trend in progression-free survival demonstrated in the results of the phase II BAROCCO trial for cediranib plus olaparib for women with heavily pretreated platinum-resistant ovarian cancer, “the combination represents an active, feasible, oral regimen that deserves further investigation,” said Nicoletta Colombo, MD, of Istituto Europeo di Oncologia, Milan, and colleagues. In a presentation at the European Society for Medical Oncology (ESMO) Congress 2019 in Barcelona (Abstract LBA58), Dr. Colombo noted that the results with the combination of an inhibitor of VEGF receptor tyrosine kinases and a PARP inhibitor were not statistically significant, but that BAROCCO included a difficult-to-treat population with a high unmet need.
The study’s rationale, in part, is that “hypoxia induced by antiangiogenic agents could cause a functional impairment of homologous recombination, thus sensitizing wild-type BRCA tumor cells to PARP inhibition,” noted Dr. Colombo and colleagues in the abstract. BAROCCO randomly assigned 123 patients (109 with germline BRCA wild-type disease) 1:1:1 to receive paclitaxel (control arm), oral olaparib daily together with cediranib daily (continuous-schedule arm), or olaparib with cediranib given 5 days per week (intermittent-schedule arm) until disease progression.
In the experimental arms, 85% of patients saw a clinical benefit, according to the investigators. However, “the interruption of cediranib administration for 2 days may have a detrimental effect on progression-free survival with no advantage [regarding] toxicity,” they noted. Although the estimated hazard ratio for progression-free survival in the continuous arm versus the control arm was 0.76 (P = .28 by log-rank test), it was 1.08 in the intermittent arm versus the control arm (P = .76 by log-rank test).
In the control, continuous, and intermittent arms, the median progression-free survival for the 123 patients was 3.1, 5.7, and 3.8 months, respectively, whereas in the subgroup with BRCA wild-type disease, the progression-free survival was 2.1, 5.8, and 3.8 months, respectively.
Disclosure: For full disclosures of the study authors, visit esmo.org.