Cediranib–Olaparib No Benefit Over Standard Care In Platinum-Sensitive Recurrent Ovarian Cancer

Author: By Laura Cowen, medwireNews Reporter 

medwireNews: A platinum-free combination of cediranib plus olaparib does not offer better progression-free survival (PFS) than standard platinum-based chemotherapy in women with recurrent platinum-sensitive ovarian cancer, show phase III data presented at the virtual 2020 ASCO Annual Meeting. 

“Overall, although NRG-GY004 did not meet its primary endpoint, non-platinum therapies may still offer alternatives in women with recurrent platinum-sensitive ovarian cancer and can be feasibly explored in future studies in this setting”, remarked presenting author Joyce Liu, from the Dana-Farber Cancer Institute in Boston, Massachusetts, USA. 

Of the 528 women included in the open-label study, 187 were randomly assigned to receive platinum-based standard of care (carboplatin/paclitaxel, carboplatin/gemcitabine, or carboplatin/liposomal doxorubicin), 189 were assigned to receive cediranib 30 mg/day plus olaparib 200 mg twice daily, and 189 were given olaparib 300 mg twice daily. 

All patients had recurrent platinum-sensitive (>6-month platinum-free interval), high-grade, serous, endometrioid, or BRCA-related ovarian cancer that had been treated with a maximum of one prior non-platinum therapy and unlimited prior platinum therapies, excluding PARP and VEGFR inhibitors except for bevacizumab. 

After a median 29.1 months of follow-up, median PFS was 10.3 months with platinum-based chemotherapy, 10.4 months with cediranib plus olaparib and 8.2 months with olaparib monotherapy. 

The difference in PFS between chemotherapy and cediranib plus olaparib was not statistically significant and the null hypothesis was thus not rejected. Additional treatment comparisons could not be statistically interpreted due to the hierarchical testing design. 

The objective response rates were 71.3%, 69.4% and 52.4% with chemotherapy, cediranib plus olaparib and olaparib monotherapy, respectively, meaning that there was a significantly poorer response to olaparib than chemotherapy, while overall survival (OS) was 31.3, 30.5 and 29.2 months, respectively. Joyce Liu noted, however, that the OS data are not yet mature. 

Among the 134 patients with a germline BRCA mutation, median PFS was 10.5, 18.0 and 12.7 months with chemotherapy, cediranib plus olaparib and olaparib monotherapy, respectively, prompting the presenter to say that “both olaparib and combination cediranib-olaparib demonstrated substantial activity” in this subgroup, with biomarker investigation now ongoing. 

The corresponding durations among BRCA wild-type patients were 9.7, 8.9 and 6.6 months. 

No new safety signals were identified for cediranib plus olaparib and, “as expected”, hematologic adverse events (AEs) occurred at higher rates with chemotherapy whereas non-hematologic AEs were more common with the non-platinum combination, Joyce Liu told delegates. 

Treatment discontinuations due to AEs were reported in 15.0% of the chemotherapy group, 21.2% of the cediranib plus olaparib group and 8.5% of the olaparib group. 

Joyce Liu concluded: “Combination cediranib-olaparib did not meet the primary endpoint of improved PFS compared to platinum-based chemotherapy, although comparable clinical activity in terms of both PFS and objective response rates were observed.” 

Reference  

Liu JF, Brady MF, Matulonis UA, et al. A phase III study comparing single-agent olaparib or the combination of cediranib and olaparib to standard platinum-based chemotherapy in recurrent platinum-sensitive ovarian cancer. J Clin Oncol 38: 2020 (suppl; abstr 6003). DOI: 10.1200/JCO.2020.38.15_suppl.6003.