Pfizer Inc. reported detailed results from the Phase 3 HER2CLIMB-05 trial showing that adding Tukysa (tucatinib) to first-line maintenance therapy significantly prolonged median progression-free survival (PFS) in patients with HER2-positive metastatic breast cancer (MBC).
In the randomized, double-blind study, patients who had completed induction therapy with trastuzumab, pertuzumab and a taxane but had not progressed received either Tukysa plus trastuzumab and pertuzumab or placebo plus the same antibody backbone. Tukysa delivered a median PFS of 24.9 months versus 16.3 months in the control arm, extending PFS by 8.6 months and reducing the risk of progression or death by 36% (hazard ratio 0.641; 95% CI: 0.514–0.799; p < 0.0001).
The benefit was consistent across hormone receptor-positive and hormone receptor-negative patients, and in patients with or without prior brain metastases. Safety remained in line with known profiles of the individual agents, with no unexpected signals from the Tukysa combinations.
Overall survival data remain immature, with around 20% of expected events reported, but early trends suggest a potential advantage.
Implications for HER2+ treatment
First-line maintenance for HER2+ MBC currently relies on trastuzumab and pertuzumab without the addition of targeted kinase inhibitors. The HER2CLIMB-05 results indicate Tukysa could become part of a chemotherapy-free maintenance approach, potentially reshaping global treatment standards if confirmed by regulators.
Tukysa is approved in the US and other markets in combination with trastuzumab and capecitabine for later-line HER2+ MBC but is not yet approved for first-line use. Pfizer said it intends to discuss the Phase 3 findings with regulatory authorities.
The data arrive as the first-line HER2+ MBC landscape shows the first signs of potential change in over a decade. AstraZeneca/Daiichi Sankyo’s HER2-targeted antibody drug conjugate (ADC) Enhertu (trastuzumab deruxtecan) recently reported positive Phase 3 results in the DESTINY-Breast09 trial, where Enhertu plus pertuzumab reduced the risk of progression or death by 44% versus standard THP (taxane, trastuzumab, pertuzumab). Another HER2 ADC under development is Ambrx’s ARX788, with Phase 3 data for the molecule compared with lapatinib plus capecitabine posted earlier this year.