Results of the HER2CLIMB-02 study: Prof François Duhoux meets Prof Sara Hurvitz

Prof Sara Hurvitz, medical oncologist and clinical research leader at Fred Hutchinson Cancer Center in Seattle, discusses with Prof François Duhoux, medical oncologist and head of clinic of the department of oncology at the Cliniques Universitaires in Brussels, on her presentation during the general session 1 at SABCS 2023, in which she communicated first results of the HERCCLIMB-02 study.  

The HER2CLIMB-02 study aimed to assess the benefits and safety of adding tucatinib to trastuzumab emtansine (T-DM1) in patients with HER2-positive breast cancer. It included approximately 460 patients randomly assigned to receive either T-DM1 plus tucatinib or T-DM1 plus placebo. The primary endpoint was PFS, with an interim analysis for overall survival if the primary endpoint was met. Importantly, patients with brain metastases, including those with active or untreated metastases, were allowed to participate, constituting 44% of the enrolled patients.

The study showed that the addition of tucatinib statistically significantly improved median PFS by approximately two months, with a 24% relative risk reduction (hazard ratio of 0.76). Notably, there was a strong trend toward improved PFS in patients with brain metastases. However, overall survival data were immature at the time of the analysis. Patients in the control arm receiving T-DM1 alone showed a somewhat lower PFS than observed in the EMILIA trial, likely attributed to the more heavily pretreated nature of this patient population and the availability of pertuzumab.

In terms of side effects, the addition of tucatinib led to an increased rate of grade 3 or greater adverse events, including nausea, vomiting, diarrhoea, and transaminase elevations. Around 16% of patients experienced grade 3 or greater transaminase elevations, which were manageable with dose adjustments.

Given the array of available treatments, the recommendation for patients without brain metastases is to consider T-DXd as the second-line regimen based on its positive outcomes in the DESTINY-Breast-03 trial. For patients with brain metastases, tucatinib has level one evidence, while T-DXd also shows activity but lacks the same level of evidence. The decision may depend on individual patient characteristics and responses to prior treatments.

Reference:

Hurvitz S. et al., HER2CLIMB-02: Randomized, Double-Blind Phase 3 Trial of Tucatinib and Trastuzumab Emtansine for Previously Treated HER2-Positive Metastatic Breast Cancer –   SABCS 2023, #GS01-10