Abstract GS5-01: Addition of platinum to sequential taxane-anthracycline neoadjuvant chemotherapy in patients with triple-negative breast cancer: A phase III randomized controlled trial

Abstract Background: Despite several studies, the impact of adding platinum on long-term outcomes in triple-negative breast cancer (TNBC) has not been definitively established. We conducted a single-centre randomized phase III trial to evaluate the efficacy and toxicity of adding platinum to standard neoadjuvant chemotherapy in these patients. Methods: Patients with histopathological diagnosis of TNBC without evidence of distant metastases who were planned to be treated with neoadjuvant chemotherapy (NACT) were randomized to experimental or control arms after stratification by menopausal status (premenopausal or perimenopausal, and postmenopausal) and stage [operable breast cancer (OBC, clinical T1-3, N0-1, M0), and locally advanced breast cancer (LABC, cT4 or N2-3, M0)]. NACT in control arm included paclitaxel 100 mg/m2 once per week for 8 weeks followed by doxorubicin (60 mg/m2) or epirubicin (90 mg/m2) plus cyclophosphamide (600 mg/m2) once every 21 days for 4 cycles while in experimental arm carboplatin (area-under-curve 2) was added once per week for 8 weeks with paclitaxel. After NACT patients received standard surgery for primary tumor and axillary lymph nodes (LN) followed by radiotherapy. The primary endpoint was disease-free survival (DFS) and the secondary endpoints were overall survival (OS), pathological complete response (pCR, absence of invasive cancer from breast and LN), and toxicity. Results: Between April 2010 and January 2020, 720 (355 control, 365 experimental) patients with a median age of 46 (25-69) years [< 50 years, 502 (69.7%), premenopausal 418 (58.2%)], were included in the study, of whom 285 (39.6%) had OBC and 435 (60.4%) had LABC, with a median clinical tumor size of 6.0 (1.2- 20.0) cm. At a median follow-up of 67.6 (18.9-142.2) months, in the experimental and control arms, the 5-year DFS were 70.6% (95% CI 65.7-75.5%) and 64.5% (95% CI 59.4-69.6%), respectively (HR 0.79, 95% CI 0.61-1.02, p=0.073), 5-year OS were 74.0 (95% CI 69.3-78.7%) and 66.7% (95% CI 61.6-71.8%), respectively (HR 0.75, 95% CI 0.57-0.98, p=0.034), and pCR were 55.2% (95% CI 49.7-69.5%) and 41.5% (95% CI 36.2-47.0%), respectively (p=0.0004). In subgroup analyses, the benefit of carboplatin was confined to patient’s < 50 years, with significant interaction between treatment and age. In women < 50 years of age, in experimental versus control arms, 5-year DFS and OS were 74.5% vs 62.3% (p=0.003, interaction p=0.003) and 76.8% vs 65.7% (p=0.003, interaction p=0.004), respectively. Addition of carboplatin had a significant beneficial impact on OS after adjusting for baseline clinical tumor size and age in a Cox model (HR 0.75, 95% CI 0.58-0.98, p=0.038). In experimental and control arms, numbers of patients with any grade >/=3 toxicity were 140 (38.5%) and 107/355 (30.14%), respectively, (p=0.02), grade >/=3 neutropenia were 2/364 (0.55%) and 1/355 (0.28%), respectively, grade >/=3 thrombocytopenia were 1/364 (0.27%) and 0 (0%), respectively, and febrile neutropenia were 26/364 (7.14%%) and 18/355 (5.07%), respectively (p=0.25). Conclusions: This study, to our knowledge the largest reported trial of neoadjuvant platinum in TNBC thus far, suggests that addition of carboplatin to sequential taxane-anthracycline neoadjuvant chemotherapy results in substantial and clinically meaningful improvement in disease-free and overall survival in young patients with TNBC and should be the standard of care in these patients. Citation Format: Sudeep Gupta, Nita S. Nair, Rohini Hawaldar, Vaibhav Vanmali, Vani Parmar, Seema Gulia, Jaya Ghosh, Shalaka Joshi, Rajiv Sarin, Tabassum Wadasadawala, Tejal Panhale, Sangeeta Desai, Tanuja Shet, Asawari Patil, Garvit Chitkara, Sushmita Rath, Jyoti Bajpai, Meenakshi Thakkur, Rajendra Badwe. Addition of platinum to sequential taxane-anthracycline neoadjuvant chemotherapy in patients with triple-negative breast cancer: A phase III randomized controlled trial [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr GS5-01.