Adding atezolizumab to adjuvant chemotherapy for stage II and III triple-negative breast cancer is unlikely to improve efficacy

Dr Michail Ignatiadis - Institut Jules Bordet, Brussels, Belgium

This is the only study that tested the value of adjuvant immunotherapy in early TNBC. So basically patients with triple-negative breast cancer, stage II or III, that have received primary surgery upfront were randomised in a one-to-one based adjuvant chemotherapy with or without atezolizumab. The primary endpoint of the study was invasive disease free survival. So we wanted to demonstrate that the addition of atezolizumab could improve invasive disease free survival for those.

What was the study design?

This was an open-label phase III trial in which patients with triple-negative breast cancer stage II or III were randomised in a one-to-one ratio between standard adjuvant chemotherapy that included weekly paclitaxel followed by four cycles of a dose-dense anthracycline-based chemotherapy regimen versus the same standard adjuvant chemotherapy together with one year of atezolizumab. The primary endpoint of the study was invasive disease-free survival.

What were the key results?

The study was stopped at the interim analysis after 62% of the IDFS events occurred. This interim analysis has been requested by a health authority. In this interim analysis, the futility boundary of 1.0 was crossed so this is a negative study. So the addition of atezolizumab did not improve invasive disease-free survival in this patient population.

What could be the impact of these results?

So just to complete the data, I have to say that no new safety signals have been identified. The addition of atezolizumab has not compromised the delivery of adjuvant chemotherapy. I think these data are very important, because they help us understand how to best give immunotherapy in TNBC. So, knowing that immunotherapy works when it is given in the neoadjuvant setting, based on the KEYNOTE-522 results, this study demonstrates for the first time that immunotherapy is not working when it is given in the adjuvant setting. So this is the first important message from this study. So, in triple-negative breast cancer, don’t give immunotherapy in the adjuvant setting.

The second important message is that worldwide, especially in community hospitals, several patients with stage II disease are being operated upfront. So this study demonstrates that this should no longer be done. Patients with stage II TNBC should no longer receive primary surgery upfront. Why? Because adjuvant immunotherapy is not working, and because they have a better option: they can be treated with neoadjuvant chemotherapy and immunotherapy. That provides benefit. So I think it can help change practice for those hospitals and those community centres that still practice primary surgery upfront for stage II disease, and make the point that this should no longer be done. So I think very important messages coming out of this study.