Dr Reed on the Investigation of Trastuzumab Deruxtecan in HER2+ Osteosarcoma

Damon R. Reed, MD, department chair, Individualized Cancer Management, program lead, Adolescent and Young Adult, program leader, Adolescent Young Adult Program, chair, Department of Individualized Cancer Management, clinical co-director, Center of Excellence for Evolutionary Therapy, Moffitt Cancer Center, discusses a phase 2 study of fam-trastuzumab deruxtecan-nxki (Enhertu) in adolescent and young adult patients with recurrent HER2-positive osteosarcoma.

Findings from a phase 2 trial (NCT04616560) presented at the 2023 ASCO Annual Meeting showed that trastuzumab deruxtecan did not elicit a sufficient response to prompt expansion into the second stage of enrollment for patients with HER2-positive cytoplasmic or membranous osteosarcoma. One patient was event free at week 24, meeting the protocol-specified definition for response. However, 7 of 9 patients received 2 cycles of treatment and experienced progressive disease at first evaluation. No unexpected toxicities occurred.

Trastuzumab deruxtecan previously displayed efficacy in patients with HER2-positive metastatic breast cancer, even in patients without significant HER2 expression, Reed explains. Although HER2 is not expressed at the same high levels in osteosarcoma compared with breast cancer, HER2 expression can occur within these patients, leading to the rationale for investigating the antibody-drug conjugate in this patient population, he says. This research could also help investigators better understand if HER2 could be a tangible to target in patients with osteosarcoma, Reed continues.

The study was designed to expand to the next stage if 2 of the 9 patients experienced a signal of efficacy. Reed and colleagues concluded that correlative studies are ongoing, and additional investigation into antigen targets and chemotherapeutic payloads are needed for patients with osteosarcoma.