Neoadjuvant chemotherapy: what does it take to tAnGo?

Use of additional chemotherapy agents is a time-proven method of achieving an incremental survival gain in early breast cancer. A decade has passed since the publication of trials showing the benefit of adding taxanes to anthracycline-based adjuvant chemotherapy. Neo-tAnGo and the companion tAnGo trial set out to test whether additional benefit could be achieved by adding gemcitabine in the neoadjuvant and adjuvant settings, respectively. Neo-tAnGo also investigated the effect of sequencing paclitaxel either before or after epirubicin and cyclophosphamide (EC). The addition of gemcitabine was not associated with an improvement in pathological complete response (pCR) or survival, consistent with other trials that incorporated gemcitabine into neoadjuvant or adjuvant chemotherapy. Administration of paclitaxel prior to EC resulted in a 5% higher pCR rate compared with the reverse sequence (P=0.03). The pCR difference did not translate into a survival advantage. Neoadjuvant therapy is an important clinical trial platform to assess the effectiveness of new agents in early and locally advanced breast cancer. Early endpoints such as pCR, serial biopsies and imaging can be used to evaluate the activity of new therapies. The link between improvements in pCR and survival in the neoadjuvant setting, and translation of benefit into the adjuvant setting is tantalisingly close - particularly in the triple negative breast cancer and HER2 positive breast cancer subtypes - but the association remains inconsistent. This editorial will contextualise the results of the Neo-tAnGo in the current and future neoadjuvant trial landscape.