Responses to Olaparib/Cediranib Combination in Ovarian Cancer Warrant Further Investigation

Joyce F. Liu, MD, MPH

Phase 3 trial results demonstrated comparable activity of cediranib and olaparib (Lynparza) with standard-of-care platinum-based chemotherapy in the treatment of recurrent platinum-sensitive ovarian cancer, despite missing the primary end point of progression-free survival (PFS) improvement. These data were presented as part of the 2020 American Society of Clinical Oncology Virtual Scientific Program.

Patients with a germline BRCA (gBRCA) mutation treated in the 3-arm trial who received both olaparib alone and the cediranib/olaparib combination had promising responses.

"Three clinical studies have suggested the potential for synergy between anti-angiogenics and PARP inhibitors," lead study author Joyce F. Liu, MD, MPH, of the Dana-Farber Cancer Institute, explained in her presentation of the data. "In pre-clinical studies in ovarian cancer cell lines, synergy between cediranib and olaparib has been observed."

For the cediranib/olaparib combination, median progression-free survival (PFS) was 10.4 months (HR, 0.856; 95% CI, 0.66-1.11; P = 0.08, 1-tail). For olaparib alone, the median PFS was 8.2 months (HR, 1.20; 95% CI, 0.93-1.54). The standard of care chemotherapy saw a median PFS of 10.3 months.

Median overall survival (OS) for the cediranib/olaparib combination was 30.5 months compared to 31.3 months for standard of care chemotherapy and 29.2 months for olaparib alone. More, overall response rate (ORR) amongst the 3 groups was 71.3%, 69.4%, and 52.4%, respectively, for standard of care chemotherapy, cediranib/olaparib, and olaparib alone.

The primary end point was PFS, with secondary end points including OS, ORR, activity in biomarker-defined populations, safety and adverse event (AE) assessment, and quality of life.

"NRG-GY004 is the first phase III trial to compare an all oral non-platinum regimen to platinum-based chemotherapy in platinum-sensitive ovarian cancer," said Liu.

Overall, 565 patients were enrolled and randomized to 3 groups: standard of care chemotherapy (n = 187), the cediranib/olaparib combination (n = 189), and olaparib alone (n = 189). Of this group of patients, 23.7% had gBRCA mutation.

Patients with gBRCA mutation who received the cediranib/olaparib combination had a PFS of 18.0 months (HR, 0.55; 95% CI, 0.73-1.30) and 12.7 months for olaparib alone (HR, 0.63; 95% CI, 0.37-1.07).

Hematologic AEs were higher among patients treated with standard of care chemotherapy, while non-hematologic AEs were more common amongst patients treated with the cediranib/olaparib combination.

Even though the research did not answer a key question regarding "whether a non-platinum therapy could improve clinical outcomes in platinum-sensitive ovarian cancer," the researchers still recommend further evaluation of this therapy to treat platinum-sensitive ovarian cancer.

"Overall, although NRG-GY004 did not meet its primary end point, non-platinum therapies may still offer alternatives in women with recurrent platinum-sensitive ovarian cancer, and GY004 demonstrated that these can be feasibly explored in future studies in this setting," concluded Liu.

^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 (NRG Oncology GY004). Presented at: 2020 ASCO Virtual Scientific Program; May 29, 2020. Abstract 6003.}

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