HER2CLIMB-02: Primary Analysis of a Randomized, Double-blind Phase 3 Trial of Tucatinib and Trastuzumab Emtansine for Previously Treated HER2-positive Metastatic Breast Cancer
Sara A. Hurvitz, MD, presents data from the phase 3 HER2CLIMB-02 study investigating tucatinib and trastuzumab emtansine in patients with previously treated HER2+ metastatic breast cancer.
Background
Tucatinib is a highly selective HER2-directed TKI1 indicated for patients with previously treated HER2+ LA/MBC, including patients with brain metastases2-6
In HER2CLIMB, adding tucatinib to trastuzumab and capecitabine demonstrated HRs for PFS, OS, and PFS in patients with brain metastases of 0.54, 0.66, and 0.48 (P≤0.005 for all), respectively3
The incidence of brain metastases in patients with HER2+ LA/MBC remains high7-9; combining HER2-directed therapies can improve patient outcomes in HER2+ LA/MBC10,11
T-DM1 is a HER2-directed ADC approved for patients with HER2+ LA/MBC previously treated with trastuzumab and a taxane12
Preclinical data have shown that the combination of tucatinib and T-DM1 results in enhanced antitumor activity compared with either agent alone13
In a phase 1b/2 study, the combination of tucatinib and T-DM1 demonstrated encouraging antitumor activity, including intracranial responses, with a manageable safety profile14
Methods
HER2CLIMB-02 is a randomized, double-blind, placebo-controlled phase III study to evaluate efficacy and safety of TUC + T-DM1 in pts with unresectable locally advanced or metastatic HER2+ breast cancer; ∼460 pts randomized 1:1 to receive 21-day cycles of TUC (300 mg PO BID) or placebo with T-DM1 (3.6 mg/kg IV).
Pts must have had prior tx with Tras and a taxane in any setting, be ≥18 yrs, with an ECOG ≤1 and histologically confirmed HER2+ MBC. Prior tx with any investigational anti-HER2 or anti-EGFR agent or HER2 TKI is not permitted.
Conclusions
Adding tucatinib to T-DM1 significantly improved PFS in patients with previously treated HER2+ LA/MBC
Median PFS was 9.5 vs 7.4 months (HR, 0.76; P=0.0163)
PFS HRs for prespecified subgroups were consistent with that of the overall population
Median PFS for patients with brain metastases was 7.8 vs 5.7 months (HR, 0.64)
OS data are immature
Types of adverse events were consistent with those previously reported for tucatinib and T-DM1
Higher rate of hepatic events in the T-DM1 + Tucatinib arm; the events were generally transient, manageable, and reversible
This is the second randomized study which included patients with brain metastases to demonstrate that a tucatinib-containing regimen delays disease progression in HER2+ LA/MBC
Hurvitz S, Loi S, O’Shaughnessy J et al. HER2CLIMB-02: Primary Analysis of a Randomized, Double-blind Phase 3 Trial of Tucatinib and Trastuzumab Emtansine for Previously Treated HER2-positive Metastatic Breast Cancer. Presented at: 2023 San Antonio Breast Cancer Symposium, December 5-9, 2023. San Antonio, Texas.