Updates to HER2CLIMB in HER2+ MBC

Volkmar Müller, MD, PhD: We should discuss the HER2CLIMB trial further because it’s a randomized trial that approved a drug in Europe and the United States. Dr Curigliano, can you briefly summarize the results of the HER2CLIMB trial? We can then discuss some of the subgroup analyses.

Giuseppe Curigliano, MD, PhD: In the primary analysis of the HER2CLIMB trial, tucatinib added to trastuzumab and capecitabine significantly improved overall survival and progression-free survival in patients with HER2 [human epidermal growth factor receptor 2]–positive metastatic breast cancer. The data analysis is complete for this. HER2CLIMB was a randomized study, comparing 2:1 tucatinib with trastuzumab and capecitabine, to placebo with trastuzumab and capecitabine. After the primary analysis and the publication from the UAE [United Arab Emirates], the protocol was amended.

Six hundred twelve patients were enrolled in HER2CLIMB, at a median follow-up of 29.6 months. The median overall survival was 24 months in the tucatinib arm vs 19 months in the placebo combination group. The median overall survival rate at 2 years was 51% for the tucatinib arm and 40% in the tucatinib-placebo combination group. The hazard ratio for overall survival across prespecified subgroups was consistent with the overall study population, independently of previous treatment or how active their sustainable gray mass was.

In the updated analysis, the median progression-free survival was 7.6 months in the tucatinib arm vs 4.9 months in the placebo arm; the data had been confirmed. Tucatinib was well tolerated with a low rate of discontinuation due to adverse events. In the final analysis, with an additional follow-up, the tucatinib combination provided a statistically significant and clinically meaningful survival benefit for all patients with HER2+ metastatic breast cancer, including the subgroups of stable inactive brain metastases, without affecting quality of life.

Volkmar Müller, MD, PhD: Those quality-of-life data were also published. It’s great to see that quality-of-life data are an integral part of drug approval, at least in Europe, and a reimbursement, for example, in Germany. Quality of life was preserved. The longer these patients were treated, the longer they had a better quality of life. We’ve had many achievements for those patients.

Transcript edited for clarity.