Avastin Regimen Improves Survival in Ovarian Cancer, Including Some HRD-Positive Tumors

Patients with newly diagnosed ovarian cancer without a BRCA1/2 mutation treated first with chemotherapy plus Avastin (bevacizumab) and Imfinzi (durvalumab) then with maintenance Avastin plus Imfinzi and Lynparza (olaparib) had a sign

ificant improvement in survival without disease progression compared with maintenance Avastin alone.

Results from an analysis of the ongoing phase 3 DUO-O trial were presented during a press briefing for the 2023 American Society of Clinical Oncology Annual Meeting.

Findings indicated that in a non–BRCA-mutant homologous recombination deficient (HRD)–positive tumor population, the median progression-free survival (the time during and after treatment when a patient with cancer lives without disease worsening) was 37.3 months in the maintenance triplet arm versus 23 months in the maintenance Avastin alone arm. In each respective treatment arm, the progression-free survival rate was 90% versus 85% at 12 months; 84% versus 69% at 18 months; and 70% versus 46% at 24 months.

Of note, cancer cells in patients with HRD-positive tumors are unable to repair themselves.

The median progression-free survival was 24.2 months in the maintenance triplet arm versus 19.3 months in the maintenance Avastin alone arm. In each respective treatment arm, the progression-free survival rate was 81% versus 73% at 12 months; 71% versus 55% at 18 months; 51% versus 32% at 24 months.

Maintenance treatment with Avastin plus Imfinzi yielded a median progression-free survival of 20.6 months, which was an improvement compared with maintenance Avastin alone but lacked statistical significance. Maintenance Avastin plus Imfinzi produced 12-, 18-, and 24-month progression-free survival rates of 72%, 56%, and 39%, respectively.

Moreover, maintenance Avastin plus Imfinzi and Lynparza produced a median progression-free survival of 20.9 months versus 17.4 months with maintenance Avastin alone in the HRD-negative population.

Additionally, the progression-free survival with the maintenance doublet in those with HRD-positive disease was 24.4 months, with corresponding 12-, 18-, and 24-month rates of 85%, 76%, and 51%, respectively. Moreover, the median progression-free survival was 15.4 months, with 12-, 18-, and 24-month rates of 63%, 42%, and 31%, respectively.

“A (progression-free survival) effect was observed across all subgroups for the (maintenance Avastin plus Imfinzi and Lynparza) versus (maintenance Avastin alone) comparison,” said presenting author Dr. Carol Aghajanian, chief of Gynecologic Medical Oncology Service at Memorial Sloan Kettering Cancer Center in New York.

In the phase 3 DUO-O trial, patients with newly diagnosed stage 3 to 4 high-grade epithelial ovarian cancer were randomly assigned to one of three treatment arms. In the chemotherapy phase of the trial, patients received chemotherapy consisting of carboplatin/paclitaxel plus Avastin in arm 1 (378 patients) or chemotherapy plus Avastin and Imfinzi in arm 2 (374 patients) and arm 3 (378 patients).

In the maintenance phase, patients received Avastin alone for 15 months plus placebo in arm 1, Avastin for 15 months plus Imfinzi for 24 months and placebo in arm 2, or Avastin for 15 months plus Imfinzi and Lynparza for 24 months in arm 3.

The primary focus of the study was progression-free survival with maintenance Avastin alone versus maintenance triplet in the HRD-positive and overall patient populations. Other areas of interest included progression-free survival with maintenance Avastin alone versus maintenance doublet, overall survival (the time from treatment when a patient with cancer is still alive) and safety.

The most common any-grade side effects were neutropenia (low neutrophil counts, referring to a type of white blood cell), occurring in 44% of those receiving maintenance Avastin alone, 45% receiving maintenance Avastin plus Imfinzi, and 51% receiving maintenance Avastin plus Imfinzi and Lynparza. Additionally, 20%, 26%, and 35% of patients in each respective group discontinued treatment due to side effects. Overall, the safety and tolerability of the study regimens were consistent with the known profiles of each individual agent.

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