Tucatinib improves PFS in metastatic, HER2-positive breast cancer

Addition of tucatinib to trastuzumab emtansine (T-DM1) extended progression-free survival (PFS) among patients with unresectable locally advanced or metastatic HER2-positive breast cancer, according to results from the HER2CLIMB-02 trial.

HER2-positive breast cancer has a predilection to spread to the brain, and when this occurs, prognosis is poor. A previous phase 2 trial, HER2CLIMB (NCT02614794), found that the addition of tucatinib to a regimen containing the HER2-targeted antibody trastuzumab and the chemotherapy capecitabine significantly improved PFS and overall survival (OS) in heavily pretreated patients, including those with brain metastases [1,2]. Preclinical data has shown that the combination of tucatinib and T-DM1 results in enhanced antitumor activity compared with either agent alone [3]. In addition, in a phase 1b/2 study, the combination of tucatinib and T-DM1 demonstrated encouraging antitumor activity, including intracranial responses, with a manageable safety profile [4].

The phase 3 HER2CLIMB-02 trial (NCT03975647) evaluated the efficacy of the combination of tucatinib and T-DM1 in patients with HER2-positive, unresectable locally advanced or metastatic breast cancer who had progression after treatment with trastuzumab and a taxane. A total of 463 patients were enrolled and 1:1 randomised to receive tucatinib plus T-DM1 or placebo plus T-DM1; 44.1% had brain metastases at baseline. Median prior lines of systemic therapy in the metastatic setting was 1 (range 0–8). Primary outcome of the study was PFS, secondary outcomes were OS and PFS in patients with brain metastases. Prof. Sara Hurvitz (Fred Hutchinson Cancer Center, WA, USA) presented the results [5].

Median PFS in patients treated with tucatinib/T-DM1 was 9.5 months, versus 7.4 months in patients treated with placebo/T-DM1 (HR 0.76; 95% CI 0.61–0.95; P=0.0163). In patients with brain metastases, median PFS was 7.8 months and 5.7 months, respectively (HR 0.64). OS data are not yet mature.

Based on these outcomes, Prof. Hurvitz concluded that “this is the second randomised study including patients with brain metastases demonstrating that a tucatinib-containing regimen delays disease progression in patients with previously treated HER2-positive, unresectable locally advanced or metastatic breast cancer.”

1. Murthy RK, et al. N Engl J Med 2020;382:597-609.
2. Curigliano G, et al. Ann Oncol. 2022;33:321-329.
3. Olson D, et al. Cancer Res Commun. 2023;3:1927-1939.
4. Borges VF, et al. JAMA Oncol. 2018;4:1214-1220.
5. 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. Abstract GS01-10, SABCS 2023, 5–9 December, San Antonio, TX, USA.

 

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Posted on 11 January, 202411 January, 2024