Progression-Free Survival Associated With Olaparib With or Without Cediranib vs Platinum-Based Chemotherapy in Women With High-Grade Ovarian Cancer

Neither olaparib monotherapy or olaparib plus cediranib increased progression-free survival (PFS) compared with platinum-based chemotherapy in women with high-grade serous or endometroid ovarian cancer sensitive to such chemotherapy. These were the findings of an open-label, Phase III study (NRG-GY004) of 565 patients with these cancers who were randomly assigned in equal numbers to receive either platinum-based chemotherapy, olaparib, or olaparib plus cediranib between early February 2016 and mid-November 2017 (J Clin Oncol. 2022; doi:10.1200/JCO.21.02011).

The study, which was done in the United States and Canada, had PFS in the intention-to-treat population as its primary end point. Its secondary end points were 1) patient-reported outcomes (PROs) and 2) clinical activity in patient subgroups with germline BRCA-mutated or BRCA wild-type ovarian cancer.

Although platinum-based chemotherapy is the standard of care for platinum-sensitive ovarian cancer, complications result when it is infused repeatedly. Therefore, the researchers decided to compare the activity of two non-platinum-based alternative treatments, olaparib or olaparib plus cediranib, with that of platinum-based chemotherapy.

As a result, they found that, with chemotherapy, median PFS was 10.3 months (95% CI, 8.7 to 11.2 mo). In contrast, with olaparib alone, it was 8.2 months (95% CI, 6.6 to 8.7 mo). Moreover, although median PFS with olaparib plus cediranib was 10.4 months (95% CI, 8.5 to 12.5 mo), which is similar to median PFS for chemotherapy, olaparib plus cediranib did not improve PFS compared with chemotherapy (hazard ratio [HR] 0.86; 95% CI, 0.66 to 1.10; P=0.077).

Nevertheless, both olaparib monotherapy and olaparib plus cediranib showed clinical activity, which was most evident in women with a germline BRCA mutation. For example, in those with a germline BRCA mutation, the PFS HR for olaparib plus cediranib vs. chemotherapy was 0.55 (95% CI, 0.32 to 0.94), and the PFS HR for olaparib monotherapy vs. chemotherapy was 0.63 (95% CI, 0.37 to 1.07). In contrast, in those without a germline BRCA mutation, the PFS HR for olaparib plus cediranib vs. chemotherapy was 0.97 (95% CI, 0.73 to 1.30), and the PFS HR for olaparib monotherapy vs. chemotherapy was 1.41 (95% CI, 1.07 to 1.86).

“The observed activity of olaparib/cediranib and olaparib, particularly in patients with BRCA-mutated tumors, warrants further exploration and development of non-platinum-based alternatives, especially in selected patient populations with platinum-sensitive ovarian cancer,” wrote Joyce F. Liu, MD, Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, and colleagues.

Although hematologic adverse events were more common with chemotherapy, nonhematologic adverse events were more common with olaparib plus cediranib. Moreover, patients who evaluated treatment in terms of PROs (n=489) rated olaparib plus cediranib more than 1 point worse than chemotherapy (97.5% CI, −2.0 to −0.2, P=0.0063) on the Disease Related Symptoms-Physical subscale of the National Comprehensive Cancer Network-Functional Assessment of Cancer Therapy Ovarian Symptom Index. However, no difference in this score was found between olaparib and chemotherapy.

These findings led to the conclusion that “Combination olaparib/cediranib did not improve PFS compared with chemotherapy and resulted in reduced PROs.”