HER’d that.

Top Line: Do radiation and HER2-targeted therapy result in additive toxicity?

The Study: Adjuvant HER2 targeted therapy is often administered at the same time as adjuvant radiation for breast cancer. The first study evaluated whether left-sided breast radiation affects left ventricular ejection fraction (LVEF) and the risk of cardiac events in women receiving adjuvant trastuzumab. Among >3300 women treated on the landmark HERA trial, 38% received left-sided RT, 38% received right-sided RT, and 24% received no RT. Decline in LVEF and the rates of cardiovascular events (1% or less in all arms) were similar among groups, and multivariate analysis found no association between RT use or sidedness and cardiovascular events. Ok, great. Trastuzumab and RT appear safe, but what about trastuzumab emtansine (T-DM1)? Adjuvant T-DM1 is indicated for residual HER2-positive breast after neoadjuvant chemo. In the KATHERINE trial, the rate of radiation pneumonitis, though low, was numerically higher with T-DM1 (1.5% v 0.7%). Separately, the ATEMPT trial evaluated whether adjuvant T-DM1 alone had less toxicity than paclitaxel and trastuzumab for women with stage 1, node-negative, HER2-positive breast cancer. It didn’t, but this secondary analysis explored whether T-DM1 concurrent with adjuvant RT increased toxicity compared to RT concurrent with trastuzumab. The rate of grade 2+ skin toxicity was numerically (but not significantly) higher in the T-DM1 arm (33.9% v 23.2%). The rate of pneumonitis was low and similar in both arms (~1%). In a more shocking development, the 40-42% of patients in each arm that received hypofractionated whole breast radiation had a significantly lower rate of grade 2+ skin toxicity compared to those who had conventional fractionation (17.9% v 44.7%).

TBL: Radiation does not appear to affect cardiac function or the risk cardiovascular events in women receiving trastuzumab, and toxicity with concurrent T-DM1 appears comparable to that of trastuzumab. | Bachir, Int J Radiat Oncol Biol Phys 2022 & Bellon, Int J Radiat Oncol Biol Phys 2022