Pfizer Inc. has announced positive topline results from its Phase 3 HER2CLIMB-05 trial, evaluating the tyrosine kinase inhibitor TUKYSA® (tucatinib) in combination with trastuzumab and pertuzumab as first-line maintenance therapy for patients with human epidermal growth factor receptor 2-positive (HER2+) metastatic breast cancer (MBC).
The study compared TUKYSA versus placebo, both given alongside standard-of-care maintenance therapy (trastuzumab plus pertuzumab) following induction chemotherapy. The trial successfully met its primary endpoint, showing a statistically significant and clinically meaningful improvement in progression-free survival (PFS), as assessed by investigators, in the TUKYSA arm compared with placebo.
Pfizer reported that the combination of TUKYSA with trastuzumab and pertuzumab was well tolerated, with a safety profile generally consistent with that of the individual therapies.
“HER2+ breast cancer is a particularly challenging subtype, with many patients experiencing disease progression despite effective treatments in the first-line setting,” said Erika Hamilton, M.D., principal investigator of HER2CLIMB-05 and Director, Breast Cancer Research, Sarah Cannon Research Institute (SCRI). “The HER2CLIMB-05 results demonstrate that the addition of TUKYSA to first-line maintenance therapy may further lower the risk of disease progression or death, with a treatment that has a well-established safety profile.”
HER2 is overexpressed in approximately 15–20% of breast cancers and is associated with poorer prognosis. The five-year survival rate for HER2+ metastatic breast cancer is estimated to be 41–47%, depending on hormone receptor status. First-line maintenance standards have remained largely unchanged since 2012, and most HER2+ MBC patients experience disease progression within two years of starting therapy.
“Pfizer aims to help shape the future of front-line treatment for HER2+ MBC, where we see significant opportunity for a chemotherapy-free maintenance approach,” said Johanna Bendell, M.D., Chief Development Officer, Oncology, Pfizer. “The positive results from HER2CLIMB-05, combined with TUKYSA’s known safety profile in later-line settings, underscore its potential to play a meaningful role in front-line maintenance, where it may benefit a broader population of patients with HER2+ disease. We are grateful to the patients and investigators who contributed to this important research.”
Detailed results from HER2CLIMB-05 will be presented at an upcoming medical congress and shared with regulatory authorities.
Since its FDA approval in 2020, TUKYSA has become a standard of care for HER2+ MBC patients in the third-line setting and is now approved in more than 50 countries. In the U.S., TUKYSA is approved for use in combination with trastuzumab and capecitabine for adults with advanced unresectable or metastatic HER2+ breast cancer, including those with brain metastases, who have received at least one prior anti-HER2 regimen. TUKYSA is not yet approved for first-line treatment.
