What is the optimal chemotherapy regimen for vulnerable older patients with ovarian cancer?
In this randomized clinical trial of 120 vulnerable older patients with ovarian cancer, single-agent carboplatin was less feasible and active than a conventional every-3-weeks carboplatin–paclitaxel regimen (6 cycles completed in 48% vs 60% of patients, respectively), with significantly worse progression-free and overall survival outcomes, leading to premature termination of the trial.
Despite relatively high toxic effects, a conventional doublet regimen should be offered to all older adult patients with ovarian cancer, irrespective of vulnerability.
Single-agent carboplatin is often proposed instead of a conventional carboplatin–paclitaxel doublet in vulnerable older patients with ovarian cancer. Such an approach could have a detrimental effect on outcomes for these patients.
To compare the feasibility, efficacy, and safety of single-agent carboplatin every 3 weeks, weekly carboplatin–paclitaxel, or conventional every-3-weeks carboplatin–paclitaxel in vulnerable older patients with ovarian cancer.
Design, Setting, and Participants
This international, open-label, 3-arm randomized clinical trial screened 447 women 70 years and older with newly diagnosed stage III/IV ovarian cancer by determining their Geriatric Vulnerability Score; 120 patients with a Geriatric Vulnerability Score of 3 or higher were stratified by country and surgical outcome. Enrollment took place at 48 academic centers in France, Italy, Finland, Denmark, Sweden, and Canada from December 11, 2013, to April 26, 2017. Final analysis database lock April 2019. Data analysis was performed from February 1 to December 31, 2019.
Patients were randomized to receive 6 cycles of (1) carboplatin, area under the curve (AUC) 5 mg/mL·min, plus paclitaxel, 175 mg/m2, every 3 weeks; (2) single-agent carboplatin, AUC 5 mg/mL·min or AUC 6 mg/mL·min, every 3 weeks; or (3) weekly carboplatin, AUC 2 mg/mL·min, plus paclitaxel, 60 mg/m2, on days 1, 8, and 15 every 4 weeks.
Main Outcomes and Measures
The primary outcome was treatment feasibility, defined as the ability to complete 6 chemotherapy cycles without disease progression, premature toxic effects–related treatment discontinuation, or death.
A total of 120 women were randomized. The mean and median age was 80 (interquartile range, 76-83; range, 70-94) years; 43 (36%) had a Geriatric Vulnerability Score of 4 and 13 (11%) had a Geriatric Vulnerability Score of 5; 40 (33%) had stage IV disease. During its third meeting, the independent data monitoring committee’s recommendation led to the termination of the trial because single-agent carboplatin was associated with significantly worse survival. Six cycles were completed in 26 of 40 (65%), 19 of 40 (48%), and 24 of 40 (60%) patients in the every-3-weeks combination, single-agent carboplatin, and weekly combination groups, respectively. Treatment-related adverse events were less common with the standard every-3-weeks combination (17 of 40 [43%]) than single-agent carboplatin or weekly combination therapy (both 23 of 40 [58%]). Treatment-related deaths occurred in 4 patients (2 of 40 [5%] in each combination group).
Conclusions and Relevance
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.
ClinicalTrials.gov Identifier: NCT02001272
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Falandry C, Rousseau F, Mouret-Reynier M, et al. Efficacy and Safety of First-line Single-Agent Carboplatin vs Carboplatin Plus Paclitaxel for Vulnerable Older Adult Women With Ovarian Cancer: A GINECO/GCIG Randomized Clinical Trial. JAMA Oncol. 2021;7(6):853–861. doi:10.1001/jamaoncol.2021.0696
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