Dr Gorantla on Treatment Patterns With HER2-Directed Therapy Across Breast Cancer Subsets

“In terms of hormone receptor–negative, HER2-positive breast cancer, [treatments of physician’s choice were] pretty evenly divided [between] T-DXd and tucatinib-based therapy.”

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

A real-world study addressed this critical clinical gap, as determining the optimal second-line therapy for patients with intracranial involvement remains a challenge despite T-DXd being a preferred guideline-recommended option and tucatinib plus trastuzumab and capecitabine having established intracranial activity.

The study used the Integra PrecisionQ Deidentified Database, a robust repository containing data from approximately 2.2 million patients, including over 500,000 patients with breast cancer. Gorantla and colleagues identified 255 eligible patients who had progressed on first-line therapy and initiated second-line treatment after January 1, 2020. Of these patients, 138 (54%) received T-DXd and 117 (46%) received tucatinib plus trastuzumab and capecitabine. This real-world approach allowed for the inclusion of patients with complex histories and comorbidities, who are often excluded from phase 3 clinical trials.

Gorantla noted significant trends in oncologist behavior and patient characteristics across the 2 groups. Although treatment choice was evenly divided for patients with hormone receptor–negative, HER2-positive disease, 64% of patients with hormone receptor–positive, HER2-positive disease were treated with T-DXd. Data from the poster further revealed that the T-DXd cohort was slightly older (median age 58 years vs 55 years; P = .026) and had a lower proportion of obese patients (17% vs 29%; P = .026) compared with the tucatinib group. Additionally, Gorantla explained that oncologists appeared comfortable using T-DXd in more clinically challenging cases, as the T-DXd group had a higher proportion of patients with an ECOG performance status of 2 or greater.

The primary end point of real-world time to next treatment (TTNT) favored the T-DXd group, with a median of 17 months compared with 11 months for the tucatinib group (P = .006). A multivariate Cox proportional hazards model confirmed that T-DXd was associated with a 48% reduction in the likelihood of requiring subsequent therapy (HR: 0.52; 95% CI, 0.37-0.74; P < .001).

However, Gorantla emphasized that overall survival data from this study are unavailable due to frequent treatment crossover in the real-world setting. He highlighted that the study does not yet capture the nuances of treating beyond progression, such as when a patient develops a new brain lesion but stays on their current systemic therapy after receiving localized radiation.