Olaparib and Cediranib vs Chemotherapy for Platinum-Sensitive Ovarian Cancer

Oral nonplatinum therapies olaparib and cediranib each demonstrated a clinical advantage in progression-free survival (PFS) over chemotherapy in patients with ovarian cancer and germline BRCA variants, according to a phase 3 trial. However, combination olaparib-cediranib did not improve PFS vs chemotherapy in the patient population as a whole.

“Platinum-based chemotherapy is the standard of care for platinum-sensitive ovarian cancer, but complications from repeated platinum therapy occur,” wrote lead author Joyce Liu, MD, Dana-Farber Cancer Institute, Boston, and colleagues.

In NRG-GY004, an open-label study conducted in the United States and Canada. Between February 04, 2016, and November 13, 2017, 565 patients were randomized in a 1:1:1 ratio to platinum-based chemotherapy, olaparib, or olaparib plus cediranib.

The primary end point was PFS in the intention-to-treat population. Secondary end points included activity within germline BRCA-mutated or wild-type subgroups and patient-reported outcomes (PROs).

Median PFS was 10.3 (95% CI, 8.7 to 11.2) months with chemotherapy, 8.2 months (95% CI, 6.6 to 8.7) with olaparib, and 10.4 (95% CI, 8.5 to 12.5) months with olaparib plus cediranib. Combination therapy with olaparib plus cediranib did not improve PFS versus chemotherapy (hazard ratio [HR] 0.86; 95% CI, 0.66 to 1.10; P = .077).

In patients with a germline BRCA mutation, the PFS HR versus chemotherapy was 0.55 (95% CI, 0.32 to 0.94) for olaparib plus cediranib, and 0.63 (95% CI, 0.37 to 1.07) for olaparib. In patients without a germline BRCA mutation, the PFS HR versus chemotherapy were 0.97 (95% CI, 0.73 to 1.30) and 1.41 (95% CI, 1.07 to 1.86), respectively.

Hematologic adverse events occurred more commonly with chemotherapy, but nonhematologic adverse events were higher with olaparib plus cediranib.

Of the cohort, 489 patients were evaluable for PROs. Patients receiving combination olaparib plus cediranib scored on average 1.1 points worse on the NCCN FACT-Ovarian Symptom Index Disease-Related Symptoms-Physical (NFOSI-DRS-P) subscale compared with chemotherapy (97.5% CI, –2.0 to –0.2, P = .0063).

Source:
Liu J, Brady M, Matulonis U, et al. Olaparib With or Without Cediranib Versus Platinum-Based Chemotherapy in Recurrent Platinum-Sensitive Ovarian Cancer (NRG-GY004): A Randomized, Open-Label, Phase III Trial. J Clin Oncol. Published online March 15, 2022. doi:10.1200/JCO.21.02011.