Treatment With Bevacizumab for 30 Months Provides No Benefit Over 15 Months in Ovarian Cancer

Lengthening treatment with bevacizumab (Avastin) plus chemotherapy for up to 30 months did not prolong survival or improve outcomes vs the standard 15-month duration in patients with newly diagnosed stage IIB to IV ovarian, fallopian tube, or peritoneal cancer, according to data from the phase 3 AGO-OVAR 17 BOOST/GINECO OV118/ENGOT Ov-15 trial (NCT01462890).

There was no difference in progression-free survival (PFS) between the standard 15-month and experimental 30-month treatment arms (HR 0.99; 95% CI, 0.85-1.15; P = .90). Median PFS was 24.2 months in the standard arm vs 26.0 months in the extended arm, and restricted mean PFS was 39.5 vs 39.3 months, respectively. There was also no difference in overall survival (OS; HR 1.04; 95% CI, 0.87-1.23; P = .68), with medians of 54.3 months in the standard arm vs 60.0 months in the experimental arm and restricted means of 60.4 vs 60.8 months, respectively. Objective responses occurred in 26% of patients in the standard arm (n = 121) vs 27% of those in the experimental arm (n = 123; P = .87).

“To the best of our knowledge, the only other large prospective study of front-line bevacizumab-containing therapy showing PFS exceeding 2 years is the single-arm phase IIIB ROSiA study, in which bevacizumab was administered for up to 24 months. Until now, the most plausible hypothesis for the median PFS…in ROSiA was the extended treatment duration of bevacizumab, but evidence from AGO-OVAR 17 BOOST contradicts this hypothesis,” the investigators wrote.

Between November 11, 2022, and August 6, 2013, the trial randomly assigned 927 patients with newly diagnosed epithelial ovarian, fallopian tube, or primary peritoneal cancer underwent either standard (n = 464) or experimental (n = 463) treatment durations with bevacizumab. The median ages of patients were 61 years (range, 25-86) in the standard arm and 60 years (range, 21-89) in the experimental arm. Most patients in each respective arm had an ECOG performance status of 0 or 1 (95% vs 96%), a primary ovarian tumor (84% vs 84%), and high-grade serous disease (78% vs 79%). Approximately half of all patients had FIGO stage IIB to IIIC disease with no residual tumor, while the other half had stage IIB to IIIC with residual tumor or stage IV disease. Roughly 4% of patients in each arm had not undergone surgery.

Patients received paclitaxel at 175 mg/m² and carboplatin at area under the curve (AUC) 5 once every 3 weeks for 6 cycles. They also received bevacizumab at 15 mg/kg once every 3 weeks for either 22 cycles (15 months) in the standard arm or 44 cycles (30 months) in the experimental arm unless chemotherapy was initiated within 4 weeks following surgery, in which case the agent was withheld from the first cycle. Moreover, bevacizumab treatment continued even if one or both chemotherapy agents were discontinued before disease progression. There was no substantial difference between the arms in mean relative dose intensity.

Almost all patients in the standard and experimental arms, respectively, experienced AEs (99% vs 99%) and roughly two-thirds experienced AEs of grade 3 or higher (63% vs 68%). Across the treatment period, serious AEs occurred in 44% vs 46% of patients in the standard and experimental arms, respectively, and AEs of special interest occurred in 29% vs 34%. There were 8 fatal AEs in the standard arm including 2 cases of multiple organ dysfunction syndrome, 2 cases of sepsis, and 1 case each of cerebrovascular accident, mesenteric artery embolism, metastases to the kidney, and myocardial infarction. The experimental arm, meanwhile, had 2 fatal AEs that included an event of abdominal abscess and dehydration. The extended experimental treatment duration was associated with small increases in hypertension and proteinuria of grade 3 or higher; no other differences between the treatment arms were noted.

Reference

Pfisterer J, Joly F, Kristensen G, et al. Optimal treatment duration of bevacizumab as front-line therapy for advanced ovarian cancer: AGO-OVAR 17 BOOST/GINECO OV118/ENGOT Ov-15 open-label randomized phase III trial. J Clin Oncol. Published online November 4, 2022. doi:10.1200/JCO.22.01010