Tukysa Plus Trastuzumab and Pertuzumab Approved for First-Line HER2+ Breast Cancer Maintenance

The FDA has approved tucatinib (Tukysa, Seagen Inc., a subsidiary of Pfizer) with trastuzumab and pertuzumab for the maintenance treatment of adults with unresectable locally advanced or metastatic HER2-positive breast cancer following induction treatment.

Tucatinib, an oral HER2 tyrosine kinase inhibitor, was previously approved with trastuzumab and capecitabine for adults with HER2-positive advanced unresectable or metastatic breast cancer after one or more prior anti-HER2 treatments in the metastatic setting, according to Pfizer. The company said the new approval moves tucatinib into the front-line maintenance setting.

The FDA evaluated efficacy in HER2CLIMB-05, a randomized, double-blind, placebo-controlled phase 3 trial of 654 adults, with or without brain metastases, whose disease had not progressed after induction with 4 to 8 cycles of trastuzumab, pertuzumab, and a taxane. Patients received tucatinib or placebo, each with trastuzumab and pertuzumab. Median investigator-assessed progression-free survival (PFS), the primary outcome measure, was 24.9 months with tucatinib vs 16.3 months with placebo (hazard ratio, 0.64; 95% CI, 0.51-0.80).

According to the FDA, the prescribing information carries a boxed warning for hepatotoxicity and warnings and precautions for diarrhea, embryo-fetal toxicity, and increased serum creatinine without affecting renal function. Pfizer reported that safety in HER2CLIMB-05 was generally consistent with the known tucatinib profile, except for more severe hepatotoxicity. Hepatotoxicity was a serious adverse reaction in 3.9% of tucatinib-treated patients, including one fatal drug-induced liver injury. The company also reported five confirmed Hy's Law cases, including a fatal case, all after tucatinib rechallenge. The most common adverse reactions (≥20%) were diarrhea, musculoskeletal pain, hepatotoxicity, nausea, fatigue, rash, and vomiting.

The FDA-recommended tucatinib dosage is 300mg orally twice daily with trastuzumab and pertuzumab until disease progression or unacceptable toxicity. Overall survival, an additional efficacy outcome measure, was not mature at the time of the PFS analysis. Full prescribing information for Tukysa will be posted on Drugs@FDA, the agency said.

Sources: US Food and Drug Administration. FDA approves tucatinib with trastuzumab and pertuzumab for the maintenance treatment of HER2-positive breast cancer. News release. US Food and Drug Administration; October 7, 2026. Accessed October 7, 2026.

Pfizer Inc. Pfizer's Tukysa regimen receives FDA approval as front-line maintenance treatment for HER2+ metastatic breast cancer. Press release. Pfizer Inc.; October 7, 2026. Accessed October 7, 2026.