In a phase II trial reported in JAMA Oncology, Falandry et al found that single-agent carboplatin was associated with poorer survival vs a standard carboplatin/paclitaxel regimen as first-line treatment for stage III/IV ovarian cancer in women aged 70 or older with high geriatric vulnerability scores.
Study Details
The open-label trial included 120 women aged ≥ 70 with stage III/IV disease and Geriatric Vulnerability Score ≥ 3 from sites in France, Italy, Finland, Denmark, Sweden, and Canada. They were randomly assigned between December 2013 and April 2017 to receive six cycles of:
- Single-agent carboplatin at AUC 5 or 6 every 3 weeks (n = 40)
- A standard regimen of carboplatin at AUC 5 plus paclitaxel at 175 mg/m2 every 3 weeks (control group, n = 40)
- Weekly carboplatin at AUC 2 plus paclitaxel at 60 mg/m2 on days 1, 8, and 15 every 4 weeks (n = 40).
Patients had a median age of 80 years. The primary outcome measure was treatment feasibility, defined as ability to complete six chemotherapy cycles without disease progression, premature toxic effects–related treatment discontinuation, or death.
Key Findings
During its third meeting, the independent data monitoring committee recommended termination of the trial on the basis of significantly worse overall survival with single-agent carboplatin. Six cycles were completed by 48% of the carboplatin group, 65% of the control group, and 60% of the weekly carboplatin/paclitaxel group.
Treatment was discontinued due to toxic effects before cycle 6 in 15% of the carboplatin group, 20% of the control group, and 23% of the weekly carboplatin/paclitaxel group. Overall, treatment-related adverse events occurred in 58%, 43%, and 58% of patients. Treatment-related death occurred in two patients (4%) in each combination group.
Median progression-free survival was 12.5 months in the control group, 4.8 months in the carboplatin group, and 8.3 months in the weekly carboplatin/paclitaxel group, with a hazard ratio of 2.51 (P < .001) for the single-agent carboplatin vs control group.
Median overall survival was not reached in the control group, 7.4 months in the carboplatin group, and 17.3 months in the weekly carboplatin/paclitaxel group, with a hazard ratio of 2.79 (P < .001) for the single-agent carboplatin vs control group.
The investigators concluded, “This randomized clinical trial shows that compared with every-3-weeks or weekly carboplatin/paclitaxel regimens, single-agent carboplatin was less active with significantly worse survival outcomes in vulnerable older patients with ovarian cancer.”
Claire Falandry, MD, is the corresponding author for the JAMA Oncology article.
Disclosure: The study was supported by the French National Cancer Institute and the Nordic Cancer Union. For full disclosures of the study authors, visit jamanetwork.com.
