Dr Tarantino on Directions for Prospective Research in HER2+ Metastatic Breast Cancer

“We want [better for our patients], which is why we are trying to develop trials in this [setting].”

Paolo Tarantino, MD, PhD, a research fellow in Medicine at Dana-Farber Cancer Institute, discussed the evolving treatment paradigm for patients with HER2-positive metastatic breast cancer who progress on fam-trastuzumab deruxtecan-nxki (T-DXd; Enhertu).

For patients with HER2-positive metastatic breast cancer, the post–T-DXd treatment setting remains a clinical challenge, primarily due to a lack of robust prospective data in this setting, Tarantino began. Currently, no prospective clinical trials are specifically evaluating therapies in patients with prior exposure to T-DXd, he stated. Therefore, treatment decisions in this setting rely on findings from retrospective analyses, he noted. Those data suggest that it is still possible to achieve a modest progression-free survival (PFS) benefit following disease progression on T-DXd, he explained.

For instance, data have shown that the combination of tucatinib (Tukysa), trastuzumab (Herceptin), and capecitabine yields a median PFS of approximately 5 months in this setting, which, although not optimal, reflects a small degree of efficacy, Tarantino reported. Similarly, conventional chemotherapeutic agents, such as eribulin or other cytotoxic therapies, have elicited median PFS durations in the range of approximately 4 to 5 months, he said.

Given the suboptimal outcomes seen so far following T-DXd in the HER2-positive breast cancer setting, the field has a strong impetus to develop more effective therapeutic strategies, according to Tarantino. Ongoing efforts include the investigator-initiated, single-arm phase 2 SATEEN trial (NCT06100874), which is evaluating the combination of sacituzumab govitecan-hziy (Trodelvy) and trastuzumab in patients with HER2-positive metastatic breast cancer with prior exposure to T-DXd. SATEEN will evaluate outcomes including overall response rate, PFS, overall survival, clinical benefit rate, duration of response, and safety. Other research is exploring the efficacy of microtubule inhibitor–based antibody-drug conjugates in this setting, which may represent another promising investigational approach, Tarantino concluded.