As reported in the Journal of Clinical Oncology by Copeland et al, the phase III Gynecologic Oncology Group 0212/NRG Oncology study has shown no improvement in overall survival with maintenance paclitaxel or paclitaxel poliglumex vs surveillance in patients with advanced ovarian, tubal, or peritoneal cancers.
Paclitaxel poliglumex was investigated on the basis of evidence of a reduced risk of neurotoxicity, alopecia, and hypersensitivity reactions compared with paclitaxel.
Study Details
In the open-label U.S. multicenter trial, 1,157 women with clinical complete response to first-line platinum/taxane-based treatment were randomly assigned 1:1:1 between March 2005 and January 2014 to maintenance paclitaxel at 135 mg/m2 once every 28 days for 12 cycles (n = 384), paclitaxel poliglumex at the same dose and schedule (n = 387), or surveillance (n = 386). The primary endpoint was overall survival.
At a fourth interim analysis in May 2016, the independent Data Monitoring Committee voted to stop the study for futility. For the current analysis, data were frozen and locked in February 2019.
Key Findings
Median follow-up was 8.1 years. Median overall survival was 56.8 months in the paclitaxel group (hazard ratio [HR] vs surveillance = 1.091, 95% confidence interval [CI] = 0.91–1.31, P = .343), 60.0 months in the paclitaxel poliglumex group (HR vs surveillance = 1.033, 95% CI = 0.86–1.24, P = .725), and 58.3 months in the surveillance group.
Median progression-free survival was 18.9 months in the paclitaxel group (HR vs surveillance = 0.801, 95% CI = 0.68–0.94, P = .006), 16.3 months in the paclitaxel poliglumex group (HR vs surveillance = 0.854, 95% CI = 0.73–1.0, P = .055), and 13.4 months in the surveillance group.
Grade ≥ 2 gastrointestinal adverse events occurred in 27% of patients the paclitaxel group, 20% in the paclitaxel poliglumex group, and 11% of the surveillance group. Grade ≥ 2 neurologic adverse events occurred in 36%, 46%, and 14%, respectively. Grade ≥ 3 adverse events that were more common with taxanes included neutropenia (16.6%, 21.6%, and 0.5%, overall P < .01), sensory neuropathy (5.4%, 10.0%, and 0.8%, overall P < .001), and joint/bone/muscle pain (4.8%, 8.2%, and 2.9%, overall P = .004). No deaths were considered related to study treatment.
The investigators concluded, “Maintenance therapy with paclitaxel and paclitaxel poliglumex did not improve overall survival among patients with newly diagnosed ovarian, tubal, or peritoneal cancers, but may modestly increase progression-free survival. Gastrointestinal and neurologic toxicities were more frequent in the taxane treatment arms.”
Larry J. Copeland, MD, of The Ohio State University, James Cancer Hospital, Columbus, is the corresponding author of the Journal of Clinical Oncology article.
Disclosure: The study was supported by the National Cancer Institute and by Cell Therapeutics Inc. For full disclosures of the study authors, visit ascopubs.org.
