HER2CLIMB-05: Tucatinib Added to Maintenance HP Extends PFS in HER2+ Metastatic Breast Cancer

At the San Antonio Breast Cancer Symposium in San Antonio, TX, Erika Hamilton, MD, FASCO, discussed findings from the HER2CLIMB-05 study, which evaluated adding tucatinib (Tukysa; Seagen) to first-line maintenance therapy with trastuzumab (Herceptin; Genentech) and pertuzumab (Perjeta; Genentech) (HP) following 4 to 8 cycles of induction docetaxel (Taxotere; Sanofi) plus HP (THP) without disease progression. She noted that the study met its primary endpoint, demonstrating an 8.6-month improvement in investigator-assessed progression-free survival (PFS), extending median PFS from approximately 18 months to nearly 25 months, and surpassing the 2-year threshold in the maintenance setting. Hamilton emphasized that this prolongation not only advances disease control but also allows patients more time off cytotoxic chemotherapy in the first-line setting. Although median central nervous system PFS was not reached in either arm at the time of analysis, an exploratory subset of patients with baseline brain metastases showed roughly a doubling of PFS, suggesting potential benefit for this population despite the analysis not being statistically significant.

Pharmacy Times: How do the HER2CLIMB-05 results inform the potential role of tucatinib as a maintenance therapy in HER2-positive metastatic breast cancer, particularly for prolonging disease control after first-line treatment

Erika Hamilton, MD, FASCO: So the HER2CLIMB-05 study looked at adding tucatinib to first-line maintenance HP. Currently, the standard of care is induction with taxane and HP. Patients that had 4 to 8 cycles of induction THP without disease progression were allowed to come onto the study and be randomized. They either received HP with placebo—endocrine therapy was allowed if they were ER-positive—or tucatinib with HP, again with endocrine therapy also allowed if HR-positive.

The study met the primary endpoint, which was prolongation of investigator-assessed progression-free survival. The benefit was 8.6 months, so essentially about 18 months to almost 25 months. So over that 2-year threshold in the maintenance setting, I think these are quite significant results. Not only to prolong progression-free survival, which is always a goal, but this also allows for longer time off cytotoxic chemotherapy for patients in the first-line setting.

Pharmacy Times: Given the CNS activity observed with tucatinib in earlier studies, what did HER2CLIMB-05 reveal about its impact on patients with or without baseline brain metastases during maintenance therapy?

Erika Hamilton, MD, FASCO: One of our secondary endpoints was CNS progression-free survival. At this time for follow-up, median CNS progression-free survival was not reached in either arm, so we really can't comment about that. In general, there was an exploratory analysis looking at those patients that came onto the study with known brain mets at baseline. Although this was an exploratory analysis and not statistically significant, it showed about a doubling of progression-free survival for those patients. So it does appear to be a good option for patients that have brain metastases.