TOPLINE:

In patients with triple-negative breast cancer (TNBC), adding once‑weekly carboplatin to standard neoadjuvant taxane‑anthracycline chemotherapy was associated with a significant improvement in overall survival and pathologic complete response (pCR) but not event‑free survival (EFS). In a subgroup analysis, the survival and pCR benefits of add-on carboplatin were observed in premenopausal women but not in postmenopausal patients.

METHODOLOGY:

• Breast oncologists continue to debate the role of platinum therapy in TNBC, given mixed findings from previous trials, which have reported modest improvements in pCR and inconsistent impacts on EFS and overall survival.
• To clarify the potential role of platinum therapy in the neoadjuvant setting , researchers conducted a phase 3 randomized controlled trial between April 2010 and January 2020, involving 717 patients with advanced nonmetastatic TNBC who were randomly assigned to a platinum arm (n = 361) or a control arm (n = 356).
• Patients in the control arm received neoadjuvant chemotherapy with paclitaxel at a dose of 100 mg/m² as a 1-hour infusion once per week for 8 weeks, followed by an anthracycline regimen (doxorubicin 60 mg/m² or epirubicin 90 mg/m² plus cyclophosphamide 600 mg/m²) once every 3 weeks for four cycles. Patients in the platinum arm received carboplatin plus standard neoadjuvant taxane‑anthracycline chemotherapy. Patients also underwent standard surgery (mastectomy or breast conservation) within 6 weeks of the last cycle of chemotherapy, followed by adjuvant radiotherapy per institutional guidelines.
• The primary endpoint was EFS; secondary endpoints included overall survival and pCR, with patients stratified by disease stage and menopausal status. The median follow-up duration was 67.6 months.

TAKEAWAY:

• In the modified intention-to-treat analysis, the 5-year EFS rate was slightly higher in the platinum vs control arm: 70.7% vs 64.1%; however, the EFS difference was not statistically significant (hazard ratio [HR], 0.80; P = .081). Carboplatin add-on was associated with a significant improvement in overall survival (HR, 0.74; nominal P = .029), with 5-year overall survival rates of 74.4% and 66.8%, respectively.
• Among premenopausal patients, those in the carboplatin arm demonstrated significantly improved EFS (HR, 0.61; nominal P = .003), with 5-year rates of 75.0% in the carboplatin arm compared with 59.6% in the control arm. Similarly, overall survival was significantly better in the carboplatin arm (HR, 0.57; nominal P = .002), with 5-year overall survival rates of 78.2% and 64.6%, respectively.
• The EFS and overall survival benefits did not translate to postmenopausal women. There was no difference in overall survival (HR, 1.06; 95% CI, 0.70-1.61; nominal P = .772) or EFS between the two arms (HR, 1.19; 95% CI, 0.80-1.78; nominal P = .386).
• pCR rates were significantly higher among patients who received carboplatin (54.5% vs 40.3%; nominal P < .001) and among premenopausal women (61.7% vs 40.6%; nominal P < .001) but not among postmenopausal women (44.4% vs 39.9%; nominal P = .469).
• Hematologic toxicities of grade 3 or higher, such as neutropenia, anemia, and thrombocytopenia, were more common in the carboplatin arm, although the rate of nonhematologic toxicities was similar between arms.

IN PRACTICE:

In the overall population, “adding carboplatin to standard taxane-anthracycline neoadjuvant chemotherapy significantly increased the overall survival (OS) and showed a trend toward improvement in event-free survival (EFS),” the authors concluded. However, the authors added “the benefit of adding carboplatin was confined to premenopausal patients.”

SOURCE:

The study, led by Sudeep Gupta, MD, DM, Tata Memorial Centre, Mumbai, India, was published online in Journal of Clinical Oncology.

LIMITATIONS:

The study was conducted at a single center and recruited patients over a 10-year period, which could limit generalizability. The chemotherapy backbone deviated from standard practice by using paclitaxel 100 mg/m² weekly for 8 weeks instead of the more widely used 12-week regimen, and anthracycline-cyclophosphamide was given every 21 days rather than the dose-dense 14-day schedule.

DISCLOSURES:

The authors did not disclose any funding information. Gupta disclosed receiving research funding from Roche, Sanofi, Johnson & Johnson, Amgen, Celltrion, Oncostem Diagnostics, Novartis, AstraZeneca, and Intas. Full disclosures are noted in the original article.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.