Dr O’Shaughnessy on Real-World Data for Tucatinib-Based Therapy in HER2+ Breast Cancer

Joyce A. O’Shaughnessy, MD, co-chair, Breast Cancer Research, chair, Breast Cancer Prevention Research, Baylor-Sammons Cancer Center, The US Oncology Network; member, Scientific Advisory Board, US Oncology Research Network, discusses real-world data for the use of the phase 2 HER2CLIMB trial (NCT02614794) regimen of tucatinib (Tukysa) plus trastuzumab (Herceptin) and capecitabine in HER2-positive breast cancer.

At the 2022 San Antonio Breast Cancer Symposium, investigators presented data on patient characteristics, treatment patterns, and clinical outcomes associated with tucatinib therapy in patients with HER2-positive metastatic breast cancer, based on a real-world retrospective analysis. HER2CLIMB was a randomized, placebo-controlled trial in which tucatinib in combination with trastuzumab and capecitabine (n = 612) demonstrated a statistically significant and clinically meaningful improvement in overall survival (OS) and progression-free survival (PFS) in patients with HER2-positive breast cancer compared with trastuzumab and capecitabine alone. The median OS and median PFS for patients receiving tucatinib, trastuzumab, and capecitabine was 21.9 months (95% CI, 18.3–31.0) and 7.8 months (95% CI;, 7.5–9.6), respectively.

The retrospective analysis of the real-world use of tucatinib-based treatment outside of a clinical trial setting included patients with HER2-positive breast cancer diagnosed between January 2017 and July 2022 whose information was available in the nationwide electronic health record–derived Flatiron Health Metastatic Breast Cancer database. These updated data showed that physicians were utilizing the tucatinib, trastuzumab, and capecitabine triplet in the first- or second-line setting of HER2-positive metastatic breast cancer, O’Shaughnessy says, adding that this included patients with brain metastases.

The PFS and OS data in the real-world study closely mirrored the original data from HER2CLIMB, and it was encouraging to see that benefit outside of a clinical trial setting, O’Shaughnessy explains. Although the patients were not directly comparable between the real-world and HER2CLIMB populations, tucatinib-based treatment in the real-world setting was associated with a similar median OS and median time to next treatment, which served as a proxy for PFS observed in the HER2CLIMB trial.

These findings were notable because tucatinib is associated with a survival advantage in patients with active brain metastases, and the ASCO guidelines were recently updated to reflect that the tucatinib triplet can help for patients with active, asymptomatic brain metastases forgo or postpone radiation therapy, O’Shaughnessy concludes.