Research focusing on first-line single-agent carboplatin was terminated due to an independent data monitoring committee’s recommendation after worse survival outcomes were observed in adult patients with ovarian cancer.
First-line, single-agent carboplatin was less active and produced significantly worse survival outcomes compared with carboplatin plus paclitaxel treatment options for older vulnerable patients with ovarian cancer, according to research published in JAMA Oncology.
The single-agent carboplatin treatment was compared with every-3-week or weekly carboplatin plus paclitaxel regimens to treat this cohort of women with ovarian cancer.
“Contrary to the current practice of considering single-agent carboplatin in frail patients, these results suggest that even vulnerable older women with newly diagnosed ovarian cancer should be offered carboplatin–paclitaxel combination therapy,” wrote the investigators.
The international, open-label, phase 3 clinical trial (NCT02001272) randomized 120 women to 1 of 3 arms: carboplatin plus paclitaxel every 3 weeks; single-agent carboplatin every 3 weeks; or weekly carboplatin plus paclitaxel. The median age of this cohort was 80 years (range, 70-94), with stage 4 disease reported in 40% of patients. Of this population, 36% of patients had a Geriatric Vulnerability Score of 4 and 11% had a Geriatric Vulnerability Score of 5.
The independent data monitoring committee recommended the trial be terminated at its third meeting due to single-agent carboplatin’s association with significantly worse survival. All 6 cycles of treatment were completed in 65% of patients in the carboplatin-plus-paclitaxel every 3 weeks group, 48% of patients in the single-agent carboplatin group, and 60% of patients in the weekly carboplatin plus paclitaxel group.
As for the safety profile, treatment-related adverse events were reported in 43% of patients in the carboplatin-plus-paclitaxel every 3 weeks group and 58% of patients in both the single-agent carboplatin and weekly carboplatin plus paclitaxel groups. Treatment-related deaths were reported for a total of 4 patients.
Patient enrollment was done in 48 academic centers in France, Italy, Finland, Denmark, Sweden, and Canada between December 11, 2013 and April 26, 2017.
“Management of vulnerable older patients with ovarian cancer should include, from cancer diagnosis, a personalized plan for oncogeriatric care, including both oncologic and geriatric treatment plans,” wrote the investigators. “If the oncologic plan considers the survival advantage provided by carboplatin–paclitaxel doublets, the geriatric plan must be prioritized in parallel, given the high toxic effects observed in this population, and should address the major components of the GVS (functionality, malnutrition, mood disorders).”
The 3 arms featured 6 treatment cycles of carboplatin area under the curve (AUC) 5 mg/mL, plus paclitaxel at 175 mg/m2 every 3 weeks; single-agent carboplatin AUC 5 mg/mL or AUC 6 mg/mL every 3 weeks; or weekly carboplatin AUC 2 mg/mL plus paclitaxel at 60 mg/m2. Cycles were administered on days 1, 8, and 15 every 4 weeks.
The primary end point of the research was treatment feasibility for patients. Feasibility was defined as the completion of 6 treatment cycles without disease progression, premature discontinuation due to toxic effects, or death.
The major limiting factor of the trial is the premature discontinuation of the research due to the “excess toxic effects in all groups and inferior efficacy of single-agent carboplatin.” For the combination regimens, no definitive conclusions could be drawn regarding safety, efficacy, and feasibility.
“Additional trials are merited in vulnerable older adult patients to manage severe (adverse events) without compromising outcomes,” wrote the investigators.
Falandry C, Rousseau F, Mouret-Reynier MA, et al. Efficacy and Safety of First-line Single-Agent Carboplatin vs Carboplatin Plus Paclitaxel for Vulnerable Older Adult Women With Ovarian Cancer. JAMA Oncol. doi:10.1001/jamaoncol.2021.0696