Top Line: Does immunotherapy enhance the efficacy of HER2-targeted cytotoxic therapy?
The Study: The number of effective options for subsequent lines of therapy in advanced, HER2+ breast cancer has been expanding. At the same time, immune checkpoint inhibitors (ICI) are expanding their role in triple negative breast cancer. Trastuzumab emtansine (T-DM1), an antibody-drug conjugate, is a standard treatment option for HER2+ breast cancer that progresses on trastuzumab. In the phase 2 KATE2 trial, over 200 women with advanced HER2+ breast cancer (regardless of PD-L1 status) that progressed after prior trastuzumab + taxane were randomized to receive T-DM1 with or without the ICI atezolizumab. Unfortunately, the trial was stopped early due to futility and higher adverse events with atezo. There was no difference in median progression-free survival with T-DM1 + atezo (8.2 months) compared to T-DM1 alone (6.8 months). Also, there was an increase in serious adverse events (19→ 33%) with atezo, mostly consisting of hematologic and hepatic toxicity. On a brighter note, previously reported exploratory analysis of PD-L1 positive patients suggested improved response rate and PFS in that sub-population.TBL: The non-biomarker driven addition of atezolizumab to T-DM1 increases toxicity without improving PFS among women with advanced, HER2+ breast cancer. | Emens, Lancet Oncol 2020