Data from the phase 3 ICON9 study, presented at the 2024 ESMO Congress, revealed that maintenance therapy with olaparib plus cediranib did not significantly improve progression-free survival (PFS) or overall survival (OS) compared to olaparib alone in patients with relapsed platinum-sensitive ovarian cancer.
The international, academic, controlled, randomized phase 3 trial enrolled 330 patients with relapsed platinum-sensitive ovarian, fallopian tube, and primary peritoneal cancer. Patients had a maximum of 2 prior lines of treatment and had achieved complete or partial response after a minimum of 4 cycles of chemotherapy. Patients were stratified based on tumor BRCA status, surgery vs no surgery relapse, prior treatment with bevacizumab, progression-free interval of 6 to12 months vs longer than 12 months, and country.
Study Design and Outcomes
In the ICON9 trial, patients were randomized to receive either oral olaparib at 300 mg twice daily (BD) plus oral cediranib at 20 mg once daily (OD) or 300 mg of oral olaparib BD until disease progression or clinical benefit. The primary endpoint was PFS, and secondary endpoints included OS, toxicity, adherence, quality of life (QoL), cost-effectiveness, further treatment, and response rate.
At a median follow-up of 37.0 months, the median PFS was 13.9 months in the olaparib/cediranib arm and 11.0 months in the olaparib arm (HR = 0.84; 95% CI, 0.65-1.07; P = .24). The median OS was 37.2 months in the olaparib/cediranib arm and 37.8 months in the olaparib arm (HR = 0.92; 95% CI, 0.67-1.26; P = .81).
"The improvement in progression or overall survival with maintenance olaparib and cediranib was not statistically significant compared to olaparib alone," said chief trial investigator Shibani Nicum, BSc (Hons), MBChB, MRCP, DPhil, a consultant medical oncologist and associate professor of Medical Oncology at University College Hospital London.
Safety Profile
The safety profile was generally consistent with expected toxicities from the two agents. Grade 3 or higher adverse events (AEs) occurring more frequently in the olaparib plus cediranib arm compared to the olaparib only arm included anemia (23 patients vs 20 patients), hypertension (16 patients vs 4 patients), diarrhea (16 patients vs 3 patients), fatigue (10 patients vs 5 patients), decreased neutrophil count (10 patients vs 4 patients), and abdominal pain (8 patients vs 5 patients).
Implications for Ovarian Cancer Treatment
While the combination did not demonstrate a statistically significant improvement, Dr. Nicum noted that the PFS and OS in the olaparib arm were better than anticipated, suggesting potential benefits from olaparib monotherapy in this patient population. The results highlight the complexities of treating relapsed ovarian cancer and the need for further research to optimize treatment strategies.
