A large international study suggests that adding the targeted drug tucatinib (Tukysa) to standard HER2‑directed therapy may help patients with HER2‑positive metastatic breast cancer stay in remission longer while on maintenance treatment after chemotherapy.
What is HER2CLIMB‑05 studying?
HER2CLIMB‑05 is a phase 3 clinical trial testing whether tucatinib (an oral HER2‑targeted medicine) can strengthen standard maintenance therapy with trastuzumab and pertuzumab for people with HER2‑positive metastatic breast cancer. Patients joined the study if their cancer had not grown after initial (induction) treatment and if they had no brain metastases or only brain metastases without symptoms.
More than 650 women from around the world were randomly assigned to receive either:
- Tucatinib plus trastuzumab and pertuzumab, or
- Placebo (a look‑alike pill) plus trastuzumab and pertuzumab.
Doctors then followed them to see how long it took before the cancer started to grow again (progression‑free survival) and to monitor side effects.
Key results patients should know
At the first main analysis, people who received tucatinib with trastuzumab and pertuzumab stayed free of cancer growth for a median of 24.9 months, compared with 16.3 months for those on standard therapy alone. This represents about a 36% reduction in the risk of the cancer worsening, and the benefit was seen whether or not patients had a history of brain metastases and regardless of hormone receptor status.
Overall survival data (how long patients live) are still immature and will require more follow‑up. However, these early results suggest that tucatinib may offer a meaningful extension of time before disease progression as part of first‑line maintenance therapy.
Side effects and safety
The most common side effects with tucatinib were:
- Diarrhea
- Nausea
- Increases in liver enzymes on blood tests.
Most of these were low‑grade, and only a minority were severe; about 14% of patients stopped tucatinib because of side effects. No new or unexpected safety concerns were identified, and the overall safety profile was considered manageable with monitoring and supportive care.
What this could mean for patients
These findings suggest that adding tucatinib to trastuzumab and pertuzumab after initial chemotherapy may become a new option to help people with HER2‑positive metastatic breast cancer keep their disease controlled longer while staying on maintenance treatment. Patients interested in tucatinib‑based regimens or clinical trials like HER2CLIMB‑05 can talk with their oncology team about whether this approach might be appropriate for their individual situation.
About Tukysa
TUKYSA is a prescription medicine that has been FDA approved together with trastuzumab and capecitabine to treat adults who have HER2‑positive breast cancer that:
- Has spread to other parts of the body, such as the brain (metastatic), or
- Cannot be removed with surgery.
It is approved in patients who have already received one or more other treatments that target HER2‑positive breast cancer.
Reference
Dieras V, Curigliano G, Martin M, et al. HER2CLIMB-05: A Phase 3 Study of Tucatinib Versus Placebo in Combination with Trastuzumab and Pertuzumab as First-line Maintenance Therapy for HER2+ Metastatic Breast Cancer. J Clin Oncol. 2025 Dec 10:101200JCO2502600
