Acute Toxicity With Trastuzumab Emtansine and Concurrent Radiotherapy: Non-Consecutive Case Series

In the setting of human epidermal growth factor receptor 2 (HER2)-overexpressing breast cancer, trastuzumab emtansine (T-DM1) is associated with improvements in both relapse-free and overall survival for patients with residual invasive disease after receiving neoadjuvant chemotherapy and HER2-targeted therapy. Many of these patients also undergo adjuvant radiotherapy treatment (RT); however, outside of the KATHERINE trial, there is little published data regarding the safety of this as a concurrent therapy, or when used in close sequential proximity. We report on ten cases at our institution whereby enhanced radiotherapy toxicity was observed when RT was delivered concurrently, or in close proximity to, T-DM1. Five patients experienced significant pulmonary toxicity, including early-onset radiation pneumonitis (RP), recurrent RP despite appropriate treatment, and out-of-field RP. Two patients experienced unexpected enhanced skin toxicity, one with prolonged radiation dermatitis followed by telangiectasia formation and the other with breast cellulitis requiring hospital admission. A further two developed rib fractures, one requiring surgical management and hyperbaric treatment. A final patient developed myositis. This case series supports the hypothesis that T-DM1 may enhance radiation toxicity, potentially due to its microtubule inhibitor emtansine components. Further studies are recommended to assess the potential toxicities and sequencing when combining treatment modalities. We advise clinicians to remain vigilant for unexpected toxicities and consider the potential risks in patient management of adjuvant radiotherapy when combined with T-DM1.