According to results from the phase 3 NRG-GY004 trial, neither olaparib alone nor olaparib plus cediranib improved overall survival (OS) when compared with standard-of-care treatment for patients with platinum-sensitive high-grade serous, endometrioid, or BRCA-related ovarian cancer.

These results were presented at the European Society for Medical Oncology Congress in Madrid, Spain, by lead author, Joyce F. Liu, MD, MPH, Dana-Farber Cancer Institute, Boston, Massachusetts. 

The previously reported primary analysis found “neither olaparib nor combined cediranib and olaparib improved [progression-free survival] PFS compared to standard of care [platinum] therapy as treatment for relapsed [platinum]-sensitive [ovarian cancer], although median PFS was longer in patients with [germline] BRCA [mutations],” stated Dr Liu and coauthors.

In this overall survival analysis, 565 patients with platinum-sensitive high-grade serous, endometrioid, or BRCA-related ovarian cancer were randomized on a 1-to-1-to-1 basis to receive standard of care (carboplatin plus paclitaxel, carboplatin plus gemcitabine, or carboplatin plus liposomal doxorubicin); 300mg olaparib twice daily; or 30mg cediranib once daily plus 200mg olaparib twice daily. Patients were stratified based on germline BRCA (gBRCA) status, platinum-free interval (6 to 12 vs >12 months), and prior treatment with anti-angiogenic therapy. The primary end point was OS, with analysis specified to occur when at least 265 events had occurred cumulatively in the standard of care and cediranib plus olaparib arms.

At a median follow-up of 66.5 months, 528 patients had started treatment. There were 187 patients were in the standard of care arm, 189 in the olaparib arm, and 189 in the cediranib plus olaparib arm, with 23.7% of patients harboring a gBRCA mutation. Death occurred in 419 patients and the hazard ratio (HR) for OS between olaparib and standard of care was 1.27 (95% confidence interval [CI] 0.99 to 1.62; P = 0.06) and 1.12 (95% CI 0.87 to 1.43; P = 0.38) between cediranib plus olaparib and standard of care. Median OS was 32.7 months in the standard of care arm, 31 months in the olaparib arm, and 33.5 months in the cediranib plus olaparib arm.

Among patients who harbored a gBRCA mutation, HR for OS between olaparib and standard of care was 1.39 and 1.24 between cediranib plus olaparib and standard of care. Median OS for these patients was 43.2 months in the standard of care arm, 41.3 months in the olaparib arm, and 44.8 months in the cediranib plus olaparib arm. Among non-gBRCA mutated patients, HR for OS in these comparisons was 1.26 and 1.07, respectively. At analysis, 46 patients in the standard of care arm received non-protocol therapy before disease progression and 36 patients received a PARP inhibitor (PARPi). Treatment was terminated prior to death in 27.3% of patients in the standard of care arm, 7.9% of patients in the olaparib arm, and 10.6% of patients in the cediranib plus olaparib arm.

“In NRG-GY004, neither [olaparib] nor [cediranib plus olaparib] improved OS compared to [standard of care] as treatment for relapsed [platinum]-sensitive [ovarian cancer],” concluded Dr Liu and coauthors. “These findings must be interpreted with caution given the proportion of [patients] terminating follow-up early and the number of [patients] on the [standard of care] arm who received off-protocol PARPi maintenance.”

Source:

Liu JF, Brady M, Matuloni UA, et al. Overall survival (OS) outcomes from NRG-GY004, a phase III study comparing single-agent olaparib or combination cediranib and olaparib to platinum (plat) based chemotherapy in recurrent plat sensitive ovarian cancer (OvCa). Presented at the 2023 ESMO Congress; October 20-24, 2023; Madrid, Spain. Abstract LBA45