Dr Gorantla on Outcomes With HER2-Directed Therapy in Breast Cancer and Brain Metastases

“Medical oncologists are not afraid of using T-DXd for the sicker patient population.”

Vikram C. Gorantla, MD, a physician at the University of Pittsburgh Medical Center Hillman Cancer Center, discussed findings from a real-world analysis of second-line treatment outcomes with fam-trastuzumab deruxtecan-nxki (T-DXd; Enhertu) vs tucatinib (Tukysa) plus trastuzumab (Herceptin) and capecitabine in patients with HER2-positive breast cancer and brain metastases.

This study addressed a clinical gap: optimal treatment for patients with HER2-positive metastatic breast cancer who develop brain metastases. Although T-DXd is currently the preferred second-line treatment option for these patients according to many guidelines, tucatinib-based regimens—typically a triplet involving tucatinib plus trastuzumab and capecitabine—remain a vital option due to their established intracranial activity.

This real-world study used the Integra PrecisionQ Deidentified Database, which Gorantla noted contains data from approximately 2.2 million patients, including approximately half a million patients with breast cancer. Through a rigorous curation process, Gorantla and his team identified 255 patients who met the eligibility criteria: having HER2-positive disease and documented brain metastases, having progressed on first-line therapy, and having initiated second-line treatment with either T-DXd (n = 138) or the tucatinib-based therapy (n = 117) after January 1, 2020. This real-world approach was chosen to capture the outcomes of patients who often present with more comorbidities and complex treatment histories than those typically enrolled in phase 3 clinical trials, according to Gorantla.

The primary end point of this analysis was real-world time to next treatment (TTNT). The results revealed a significant advantage for patients who received T-DXd, with a median TTNT of 17 months compared with 11 months in the tucatinib-based treatment group (P = .006). Furthermore, after adjusting for demographic and clinical variables, T-DXd was associated with a 48% reduced likelihood of requiring subsequent therapy (HR: 0.52; 95% CI, 0.37-0.74; P < .001).

Gorantla also highlighted several interesting trends regarding patient characteristics and provider behavior. The data indicated that oncologists were not hesitant to use T-DXd across patient populations, he said. For instance, compared with the tucatinib-based therapy group, the T-DXd group had a higher median age and a higher proportion of patients with a lower body mass index and an ECOG performance status of 2 or greater.