In an Indian single-center phase III trial reported in the Journal of Clinical Oncology, Gupta et al found that the addition of carboplatin to neoadjuvant sequential taxane-anthracycline chemotherapy did not improve event-free survival, the primary endpoint, in patients with triple-negative breast cancer. However, improvements in event-free and overall survival were observed in premenopausal patients.
Study Details
In the open-label trial, 717 patients (modified intention-to-treat population) from Tata Memorial Centre, Mumbai, were randomly assigned between April 2010 and January 2020 to receive neoadjuvant chemotherapy consisting of once-weekly carboplatin AUC = 2 plus paclitaxel at 100 mg/m2 for 8 weeks, followed by anthracycline (doxorubicin at 60 mg/m2 or epirubicin at 90 mg/m2) plus cyclophosphamide at 600 mg/m2 once every 3 weeks for four cycles (n = 361) or the same chemotherapy regimen without carboplatin (n = 356). The primary endpoint was event-free survival.
Key Findings
Median follow-up was 67.6 months (range = 18.9–142.2 months). Event-free survival events occurred in 111 of 361 patients in the platinum group vs 131 of 356 patients in the control group (hazard ratio [HR] = 0.80, 95% confidence interval [CI] = 0.62–1.03, P = .081); the 5-year event-free survival rate was 70.7% vs 64.1%.
Death occurred in 94 patients in the platinum group vs 121 patients in the control group (HR = 0.74, 95% CI = 0.57–0.97, nominal P = .029); the 5-year overall survival rate was 74.4% vs 66.8%.
Among premenopausal patients (n = 209 vs 209), those in the platinum group had improved event-free survival (HR = 0.61, 95% CI = 0.43–0.84, nominal P = .003), with a 5-year rate of 75.0% vs 59.6%, and overall survival (HR = 0.57, 95% CI = 0.40–0.82, nominal P = .002), with a 5-year rate of 78.2% vs 64.6%.
Among postmenopausal patients, no differences were observed in event-free survival (HR = 1.19, 95% CI = 0.80–1.78, nominal P = .386) or overall survival (HR = 1.06, 95% CI = 0.70–1.61, nominal P = .772). Statistically significant interactions between study treatment and menopausal status for event-free survival and overall survival were observed, with the addition of platinum showing benefit in premenopausal but not postmenopausal patients.
The incidence of grade ≥ 3 myelosuppression was higher in the platinum group; no differences in nonhematologic toxicities were observed.
The investigators concluded: “Carboplatin did not significantly increase [event-free survival] but significantly increased the [overall survival] in patients with [triple-negative breast cancer], with benefits confined to premenopausal patients.”
Sudeep Gupta, MD, DM, of the Department of Medical Oncology, Tata Memorial Centre, Mumbai, is the corresponding author of the Journal of Clinical Oncology article.
Disclosure: For full disclosures of all study authors, visit ascopubs.org.
