Adding tucatinib to treatment with trastuzumab and capecitabine provides a lasting overall survival (OS) benefit for patients with previously treated, HER2-positive, metastatic breast cancer, according to final results from the HER2CLIMB trial published in Annals of Oncology.1

The phase 2 trial (ClinicalTrials.gov Identifier: NCT02614794) was designed to compare tucatinib with placebo, each in combination with trastuzumab and capecitabine. The trial enrolled patients with HER2-positive, metastatic breast cancer who had previously received trastuzumab, pertuzumab, and trastuzumab emtansine in any setting.

Of the 612 patients enrolled, 410 were randomly assigned to the tucatinib arm and 202 to the placebo arm. Overall, 48% of patients had brain metastases at baseline. The patients had received a median of 4 prior lines of therapy overall and 3 prior lines in the metastatic setting.


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In the primary analysis of HER2CLIMB, the median follow-up was 14.0 months.2 At that time, there was a significant improvement in OS and progression-free survival (PFS) seen in the tucatinib arm.

In the final analysis, the median follow-up for OS was 29.6 months. The median OS was 24.7 months in the tucatinib arm and 19.2 months in the placebo arm (hazard ratio [HR], 0.73; 95% CI, 0.59-0.90; P =.004). The 2-year OS rate was 51% and 40%, respectively.

The OS benefit with tucatinib was seen across all subgroups, including in patients with brain metastases, the researchers noted.

The median PFS was improved with tucatinib as well — 7.6 months in the tucatinib arm and 4.9 months in the placebo arm (HR, 0.57; 95% CI, 0.47-0.70; P <.00001). The 1-year PFS rate was 29% and 14%, respectively.

The tucatinib combination was considered well tolerated, with a discontinuation rate of 5.9%.

The most common adverse events (AEs) in the tucatinib arm were diarrhea (81.9%), palmar-plantar erythrodysesthesia (PPE) syndrome (65.3%), nausea (60.1%), fatigue (47.8%), and vomiting (37.6%). These AEs were primarily grade 1 or 2 in nature, and their overall rates remained stable with continued follow-up, the researchers noted.

The most common grade 3 or higher AEs in the tucatinib arm (PPE syndrome, diarrhea, elevations in ALT/AST, and fatigue) remained stable with additional follow-up as well.

These results support the use of tucatinib plus trastuzumab and capecitabine in patients with previously treated, HER2-positive metastatic breast cancer, according to the researchers. They concluded that the combination “is an important treatment option in the rapidly evolving HER2+ metastatic treatment landscape.”

Disclosures: This research was supported by Seagen Inc. and Merck Sharp & Dohme Corp. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.

References

  1. Curigliano G, Mueller V, Borges V, et al. Tucatinib vs placebo added to trastuzumab and capecitabine for patients with pretreated HER2+ metastatic breast cancer with and without brain metastases (HER2CLIMB): Final overall survival analysis. Ann Oncol. Published online December 22, 2021. doi:10.1016/j.annonc.2021.12.005
  2. Murthy RK, Loi S, Okines A, et al. Tucatinib, trastuzumab, and capecitabine for HER2- positive metastatic breast cancer. N Engl J Med. 2020 ;382(7):597-609. doi:10.1056/NEJMoa1914609