In the ECOG-ACRIN EA1131 trial, platinum-based adjuvant chemotherapy in patients with (basal subtype) triple-negative breast cancer (TNBC) with residual invasive disease did not prove to be non-inferior or superior to capecitabine adjuvant chemotherapy. The trial was discontinued after the fifth interim analysis.
Patients with TNBC who have residual invasive disease after completion of neoadjuvant chemotherapy have a very high risk of recurrence . Recently, the CREATE-X trial showed this risk is reduced by adjuvant capecitabine, while pre-clinical models suggest TNBC basal subtype has increased sensitivity for platinum-based chemotherapy [2,3].
Therefore, the randomised, phase 3 ECOG-ACRIN EA1131 trial (NCT0244539) tested the hypothesis that invasive disease-free survival would be improved in patients with basal subtype TNBC with residual disease after neoadjuvant chemotherapy with the adjuvant use of platinum-based chemotherapy instead of capecitabine. The trial enrolled 410 patients (recruitment goal: 775) with clinical stage II/III TNBC post-neoadjuvant taxane ± anthracycline-based chemotherapy with at least 1 cm residual disease in the surgical specimen. Patients were randomised 1:1 to receive platinum-based adjuvant chemotherapy (carboplatin or cisplatin once every 3 weeks for 4 cycles) or capecitabine (14 out of 21 days every 3 weeks for 6 cycles). TNBC subtype (i.e basal and non-basal) was analysed in the surgical specimen by PAM50 profiling. The primary endpoint of the trial was invasive disease-free survival. A non-inferiority design (non-inferiority margin of HR of 1.154) with superiority alternative (alternative HR of 0.754) was chosen, assuming a 4-year invasive disease-free survival of 67% for the capecitabine arm. Prof. Ingrid Mayer (Vanderbilt University School of Medicine, TN, USA) presented the results of ECOG-ACRIN EA1131 after the fifth interim analysis .
After a median follow-up of 20 months and 120 invasive disease-free survival events (61% of full information) in the 308 (78%) patients with basal subtype TNBC, the 3-year invasive disease-free survival for platinum-treated patients was 42% versus 49% for capecitabine-treated patients (HR 1.06; 95% CI 0.62-1.81).
Grade 3 and 4 toxicities were more common with platinum agents. Based on these interim results, the Data and Safety Monitoring Committee recommended stopping the trial as it was unlikely that further follow-up would show non-inferiority or superiority of platinum-based chemotherapy.
- Symmans WF, et al. J Clin Oncol. 2017;35:1049-1060.
- Masuda N, et al. N Engl J Med. 2017;376:2147-2159.
- Lehmann BD, et al. J Clin Invest. 2011;121:2750-2767.
- Mayer IA, et al. A randomized phase III post-operative trial of platinum-based chemotherapy (P) versus capecitabine (C) in patients (pts) with residual triple-negative breast cancer (TNBC) following neoadjuvant chemotherapy (NAC): ECOG-ACRIN EA1131. Abstract 605, ASCO 2021 Virtual Meeting, 4–8 June.
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