Randomized Phase III Postoperative Trial of Platinum-Based Chemotherapy Versus Capecitabine in Patients With Residual Triple-Negative Breast Cancer Following Neoadjuvant Chemotherapy: ECOG-ACRIN EA1131. Issue 23 (10th August 2021)

• Record Type: Journal Article
• Authors: Mayer, Ingrid A.; Zhao, Fengmin; Arteaga, Carlos L.; Symmans, William F.; Park, Ben H.; Burnette, Brian L.; Tevaarwerk, Amye J.; Garcia, Sofia F.; Smith, Karen L.; Makower, Della F.; Block, Margaret; Morley, Kimberly A.; Jani, Chirag R.; Mescher, Craig; Dewani, Shabana J.; Tawfik, Bernard; Flaum, Lisa E.; Mayer, Erica L.; Sikov, William M.; Rodler, Eve T.; Wagner, Lynne I.; DeMichele, Angela M.; Sparano, Joseph A.; Wolff, Antonio C.; Miller, Kathy D.
• Is Part Of: Journal of clinical oncology. Volume 39:Issue 23(2021)
• Page Start: 2539
• Page End: 2551
• Publication Date: 2021-08-10
• Subjects: Oncology -- Periodicals; Cancer -- Periodicals; Oncology; Medical Oncology; Cancérologie -- Périodiques; Cancer -- Périodiques; Cancérologie; Cancer; Oncology; Oncologia; Càncer; Periodicals; 616.994
• DOI: 10.1200/JCO.21.00976
• Languages: English
• ISSNs: 0732-183X

Abstract

Abstract : PURPOSE: Patients with triple-negative breast cancer (TNBC) and residual invasive disease (RD) after completion of neoadjuvant chemotherapy (NAC) have a high-risk for recurrence, which is reduced by adjuvant capecitabine. Preclinical models support the use of platinum agents in the TNBC basal subtype. The EA1131 trial hypothesized that invasive disease-free survival (iDFS) would not be inferior but improved in patients with basal subtype TNBC treated with adjuvant platinum compared with capecitabine. PATIENTS AND METHODS: Patients with clinical stage II or III TNBC with ≥ 1 cm RD in the breast post-NAC were randomly assigned to receive platinum (carboplatin or cisplatin) once every 3 weeks for four cycles or capecitabine 14 out of 21 days every 3 weeks for six cycles. TNBC subtype (basal v nonbasal) was determined by PAM50 in the residual disease. A noninferiority design with superiority alternative was chosen, assuming a 4-year iDFS of 67% with capecitabine. RESULTS: Four hundred ten of planned 775 participants were randomly assigned to platinum or capecitabine between 2015 and 2021. After median follow-up of 20 months and 120 iDFS events (61% of full information) in the 308 (78%) patients with basal subtype TNBC, the 3-year iDFS for platinum was 42% (95% CI, 30 to 53) versus 49% (95% CI, 39 to 59) for capecitabine. Grade 3 and 4 toxicities were more common with platinum agents. The Data and Safety Monitoring Committee recommended stopping the trial as it was unlikely that further follow-up would show noninferiority or superiority of platinum. CONCLUSION: Platinum agents do not improve outcomes in patients with basal subtype TNBC RD post-NAC and are associated with more severe toxicity when compared with capecitabine. Participants had a lower than expected 3-year iDFS regardless of study treatment, highlighting the need for better therapies in this high-risk population.