Combination therapy with antibody‑drug conjugate RC48 (disitamab vedotin) and zimberelimab (PD‑1 inhibitor) successfully controlled recurrent HER2‑positive breast cancer resistant to trastuzumab emtansine: A case report

Options for later-line therapy are limited for patients with human epidermal growth factor receptor 2 (HER2)-positive breast cancer who have exhibited resistance to several systemic treatments. Antibody drug conjugates (ADCs) and immune checkpoint inhibitors are novel approaches for HER2-positive breast cancer, but few reports have been published regarding the efficacy of their combinations, particularly in patients with prior ADC failure. The present report describes a case of recurrent metastatic HER2-positive breast cancer, which responded poorly to several perioperative systemic therapies, including chemotherapies, HER2-targeted antibodies, small molecule inhibitors and trastuzumab emtansine (an ADC), along with post-surgical radiotherapy. Following failure of front-line therapies for recurrent cancer located in the chest wall, combination treatment with another HER2-targeted ADC, disitamab vedotin (120 mg), and zimberelimab (240 mg), a fully humanized anti-programmed cell death protein-1 (PD-1) antibody, administered intravenously every 2 weeks, was initiated. The tumor lesions improved slightly after two cycles of treatment and shrunk markedly, and almost disappeared at the end of the sixth cycle of therapy. The patient is still in remission at present. The present findings suggest the potential efficacy of HER2-targeted ADCs combined with PD-1 inhibitors for patients with HER2-positive breast cancer, including those resistant to prior HER2-targeted ADCs.