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In current clinical practice triple-negative breast cancer (TNBC) patients who have undergone neoadjuvant chemotherapy (NAC) and have residual disease at time of surgery are offered capecitabine as standard of care. This is based on the CREATE-X study which showed an iDFS (invasive disease-free survival) and overall survival benefit in this population, with capecitabine compared with placebo. The EA1131 study investigated the noninferiority and possible superiority of the use of platinum agents compared with capecitabine in the same clinical setting.

In the study, published in the , 410 patients with >1 cm residual disease post-NAC were randomized to platinum (cisplatin or carboplatin) every 3 weeks for four cycles versus six cycles of capecitabine. The 3-year iDFS was 42% in the platinum arm, and 49% in the capecitabine arm. Non-inferiority and superiority of platinum when compared with capecitabine was not shown.

Preclinical data have shown that the basal subtype of TNBC is more sensitive to cisplatin. However, no preferential benefit of platinum when compared with capecitabine was demonstrated in this study, regardless of intrinsic subtype. Furthermore, toxicity in the platinum arm was more severe than the capecitabine arm. Therefore, capecitabine continues to be standard of care for non-BRCA positive TNBC patients with residual disease following NAC.

The Olympia trial presented at ASCO 2021 gave us an option for the subgroup of patients with residual disease post-NAC who are positive for the BRCA mutation. The 3-year data showed that patients treated with olaparib had an iDFS benefit when compared with placebo (87.5% vs 77.1%, HR 0.58). The distant metastasis-free survival was also improved (87.5% vs 80.4%). Capecitabine or any other adjuvant chemotherapy was not allowed in this trial.

In these patients the question arises if we should be utilizing olaparib instead of capecitabine. Based on extrapolation of outcomes from the Olympiad data where olaparib was compared with physician choice of chemotherapy, which included capecitabine in the stage IV setting and the demonstrated superiority of olaparib, one could make the argument to pursue olaparib instead of capecitabine for this patient population.

The EA1131 study, however, highlighted the very low iDFS in the non-BRCA TNBC population with residual disease post-NAC. This was lower than previously reported iDFS, and is likely due to the higher disease burden at the time of surgery, and the higher proportion of patients with basal subtype, which has a worse prognosis compared with non-basal subtype, with a 3-year OS close to 60%.

This emphasizes the unmet need for more innovative therapeutics in TNBC patients, especially basal subtype and those with a significant residual disease burden post-NAC.

The place for platinum agents in early-stage breast cancer continues to be investigated, and its role is yet to be defined. Use of a platinum agent when used with anthracycline and taxane in the neoadjuvant setting improves PCR rates, but no long-term benefit has been demonstrated to date.

Some neoadjuvant trials such as KEYNOTE-522 have incorporated carboplatin in the neoadjuvant phase and may find a place in early-stage breast cancer therapy if immunotherapy becomes part of neoadjuvant armamentarium.

Rosana Gnanajothy, MD, FACP, is Assistant Professor of Hematology and Medical Oncology at Winship Cancer Institute of Emory University and the Atlanta VA Medical Center.

Read the study here and an interview about it here.