Adjuvant chemotherapy after neoadjuvant chemotherapy? Going beyond EMA/FDA

At the time of the St. Gallen Conference 2017, there was still a lack of scientific data to decide for which patients adjuvant systemic therapy should be recommended after neoadjuvant systemic therapy. However, recently, the results of the CREATE-X trial [1] and the KATHERINE trial [2] have been published. In patients with a Her2-negative tumour who had residual disease after neoadjuvant chemotherapy, the CREATE-X trial showed a clinical benefit (e.g. a reduction in recurrence and longer overall survival) of adjuvant treatment with capecitabine. In the KATHERINE trial, patients with a Her2-positive tumour who had residual disease after Her2-targeted neoadjuvant therapy had more clinical benefit from adjuvant treatment with TDM-1 compared to adjuvant treatment with trastuzumab. In line with these data, 83% of the panellists endorsed adjuvant treatment with capecitabine in patients with triple-negative breast cancer and residual disease (>1 cm residual tumour in the breast and/or positive axillary lymph nodes) following neoadjuvant chemotherapy (anthracycline/taxane). Only 6% of the panellists endorsed no further therapy. In case of residual disease less than 1 cm (and no positive axillary lymph nodes) the panellists were less in favour of adjuvant chemotherapy with capecitabine; 51% of the panellists endorsed adjuvant therapy with capecitabine vs 39% of the panellists who were in favour of no further therapy. In Her2-positive tumours and residual disease in the breast (>1 cm) or in the axillary lymph nodes following a Her2-targeted neoadjuvant therapy, 94% of the panellists endorsed adjuvant chemotherapy with TDM-1. This prompted one panellist to remark that momentarily TDM-1 is not (yet) approved for this indication by EMA and/or FDA. In case of no residual disease (e.g. a pathological complete response) following neoadjuvant therapy with polychemotherapy plus trastuzumab/pertuzumab in lymph node-positive patients with a Her2-positive tumour, 38% of the panellists endorsed adjuvant therapy with trastuzumab vs 48% of the panellists preferring dual Her2-blockade adjuvant therapy with trastuzumab plus pertuzumab. In patients benefitting from a complete remission following neoadjuvant treatment with combined polychemotherapy and trastuzumab/pertuzumab in patients with a Her2-positive lymph node-negative tumour, 52% of the panellists endorsed adjuvant therapy with trastuzumab vs 26% of the panellists preferring a dual Her2-blockade adjuvant therapy with trastuzumab plus pertuzumab.

1. Masuda N, et al. N Engl J Med 2017; 376: 2147-2159.
2. Von Minckwitz G, et al. N Engl J Med 2019; 380: 617-628.

Posted on 21 May 201929 February 2024