Dr Gorantla on a Real-World Study of HER2-Directed Breast Cancer Therapy

“We were looking at trying to understand how patients with brain metastases did in the second-line setting, after they had progressed on HER2-positive breast cancer treatment in the first-line setting.”

Vikram C. Gorantla, MD, a physician at the University of Pittsburgh Medical Center Hillman Cancer Center, discussed the rationale for conducting a real-world analysis of time to next treatment with second-line fam-trastuzumab deruxtecan-nxki (T-DXd; Enhertu) vs tucatinib (Tukysa)–based therapy in patients with HER2-positive breast cancer with brain metastases.

Gorantla emphasized the clinical challenge posed by brain metastases, which affect approximately 50% of patients with metastatic HER2-positive breast cancer during the course of their disease. This analysis studied the real-world effectiveness of T-DXd vs the triplet regimen of tucatinib, trastuzumab (Herceptin), and capecitabine. Although treatment guidelines recommend T-DXd as the preferred second-line therapy, the tucatinib-based regimen remains a significant option due to its proven intracranial activity. Gorantla noted that although clinical trials like the phase 3 DESTINY-Breast12 study (NCT04739761) showed that 61.6% (95% CI, 54.9%-67.6%) of patients with brain metastases remained progression free during T-DXd treatment at 12 months, and the HER2CLIMB trial reported a median progression-free survival of 7.6 months (95% CI, 6.2-9.5) with the tucatinib-based protocol in patients with HER2-positive metastatic disease and brain metastases, there has been a lack of real-world data directly comparing these outcomes in patients with brain metastases.

The study used the Integra PrecisionQ Deidentified Database to analyze time to next treatment (TTNT) as a primary end point. This approach was intended to reflect real-world conditions where patients often present with more comorbidities than patients enrolled in clinical trials, according to Gorantla. In real-world practice, oncologists may also use measures like radiation therapy for oligoprogression, which affects the treatment timeline, Gorantla said.

Results from a cohort of 255 patients—138 who received T-DXd and 117 who received the tucatinib-based regimen—demonstrated that the median TTNT was significantly longer for the T-DXd group, at 17 months compared with 11 months for those who received the tucatinib-based triplet (P = .006). Gorantla reported that after adjusting for demographic and clinical covariates, T-DXd was associated with a 48% reduced likelihood of requiring subsequent therapy (HR: 0.52; 95% CI, 0.37-0.74; P < .001).