Addition of Cediranib to Olaparib Fails to Induce Superior PFS in Platinum-Censitive Ovarian Cancer

A study designed to evaluate the addition of cediranib to olaparib (Lynparza) failed to meet its primary end point of improved progression-free survival (PFS), compared with chemotherapy, according to results presented at the 2020 ASCO Virtual Scientific Program.

However, study data suggested the combination showed comparable activity to standard of care platinum-based chemotherapy treatment for recurrent platinum-sensitive ovarian cancer. More, both olaparib alone and the cediranib/olaparib combination demonstrated substantial activity for patients with a germline BRCA (gBRCA) mutation.

“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 the study’s presentation. “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 (HR, 0.63; 95% CI, 0.37-1.07) for olaparib alone.

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 endpoint, 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.