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

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.

CALGB 40603 (Alliance): Long-Term Outcomes and Genomic Correlates of Response and Survival After Neoadjuvant Chemotherapy With or Without Carboplatin and Bevacizumab in Triple-Negative Breast Cancer

“…Patients assigned to carboplatin on BrighTNess had a larger absolute increase in pCR rate than on CALGB 40603 (27% v 13%) 27 and in results presented at the 2021 ESMO Congress, had significantly better 4-year EFS and a trend toward improved OS 31 although other factors might have contributed to these apparent discrepancies. Although EA1131 failed to demonstrate noninferiority of adjuvant platinum therapy compared with capecitabine in patients with TNBC with RD after (non–platinum-containing) NACT, 32 no randomized trial has reported on the addition of carboplatin to adjuvant chemotherapy for TNBC; however, one is ongoing (NRG-BR003).…”

The Clinical Value of Chemotherapy Combined With Capecitabine in Triple-Negative Breast Cancer—A Meta-Analysis

“…The results showed that the addition of capecitabine, lymph node positive and adjuvant chemotherapy were beneficial for DFS, which might be related to the anti-angiogenesis of capecitabine and the inhibition of tumor immune escape ( Pasquier et al, 2010 ). The ECOG-ACRIN EA1131 trial compared the effects of platinum preparations and capecitabine after neoadjuvant chemotherapy ( Mayer et al, 2021 ). The results showed that there was no significant difference between the effects of platinum preparations and capecitabine, and platinum preparations brought more serious toxicity.…”

Early-stage Triple-negative Breast Cancer: Time to Optimize Personalized Strategies

“…In this trial, platinum agents did not improve the 3-year iDFS in patients with basal subtype TNBC compared with capecitabine (42% vs 49%); additionally, grade 3-4 toxicities were more common in the platinum-arm. 72 These studies generally show that adjuvant capecitabine has activity in TNBC when used as an adjunct after standard anthracycline/taxane chemotherapy, but that there is no benefit in biologically unselected patients. Though the CIBOMA/GEICAM did achieve a significant OS benefit in non-basal-like TNBC, current clinical practice does not discriminate between basal and non-basal TNBC, so the results of this trial are difficult to apply in practice.…”