A long-term phase III trial found that maintenance chemotherapy did not improve overall survival over surveillance among women with advanced ovarian/fallopian tube/peritoneal cancer who had a complete response to first-line therapy.
A long-term phase III randomized trial found that maintenance chemotherapy did not improve overall survival over surveillance among women with advanced ovarian/fallopian tube/peritoneal cancer who had a complete response (CR) to first-line therapy. Maintenance chemotherapy also increased toxicity in these patients.
Treating advanced-stage ovarian cancer with surgery and chemotherapy has a high CR rate, but following those responses there is a high probability of recurrent progressive disease, said Larry J. Copeland, MD, of Ohio State University, in a presentation delivered at the Society of Gynecologic Oncology (SGO) Annual Meeting in National Harbor, Maryland. Maintenance therapy has been proposed as a way to reduce that recurrence rate and thus extend survival.
The GOG 212 study began in 2005, and closed in 2014; Copeland presented its final survival analysis. A total of 1,157 patients with stage III-IV ovarian, tubal, or peritoneal cancer who achieved a clinical CR were randomized to surveillance, paclitaxel infusion every 28 days for 12 cycles, or CT-2103 (paclitaxel poliglumex [PP]) on the same schedule. Patients were followed for a median of 71 months; several patients in each group were ineligible, were not treated, or withdrew consent, leaving 1,051 patients for analysis.
The most common disease site was the ovaries, in approximately 85% of each group, followed by the peritoneum in about 11%, and the fallopian tube in about 4%. Most patients were stage III, with serous histology.
The median overall survival was no different between the groups, at 54.8 months with surveillance, 51.3 months with paclitaxel, and 60 months with PP. The hazard ratio (HR) for paclitaxel vs surveillance was 1.104 (97.5% CI, 0.884–1.38); for PP vs surveillance, it was 0.979 (97.5% CI, 0.781–1.23).
There was a slightly extended median progression-free survival with maintenance therapy. The median PFS was 13.4 months with surveillance, compared with 18.9 months with paclitaxel, and 16.3 months with PP. For paclitaxel compared to surveillance, the HR was 0.783 (95% CI, 0.666–0.921), and for PP vs surveillance it was 0.847 (95% CI, 0.721–0.0995).
Adverse events, in particular neurotoxic events, were increased with maintenance chemotherapy. Neurotoxicity of grade 1/2 occurred in 75.4% of PP patients, and in 79.4% of paclitaxel patients, compared with 54% of surveillance patients; grade 3/4 neurotoxicities occurred in 12.4%, 7.2%, and 1.9% of those groups, respectively. Other adverse events more common with maintenance therapy included allergic reactions, fatigue, alopecia, nausea, and constipation.
Quality-of-life measures showed similar results between the groups, with some poorer outcomes with the maintenance therapy.
Though it was not prospectively measured, there was some indication that patients with R0 disease did derive benefit from the maintenance therapy. Copeland said that question, along with the possibility that maintenance chemotherapy could induce chemoresistance in these patients, remain unanswered after this study.