ONCAlert | Upfront Therapy for mRCC

Tucatinib Demonstrates Survival Benefit in HER2+ Breast Cancer, FDA Submission Impending

Jason M. Broderick
Published Online: 8:08 PM, Wed December 11, 2019
Rashmi K. Murthy, MD
Rashmi K. Murthy, MD
In the phase II HER2CLIMB trial, a 34% reduction in the risk of death was observed with the addition of tucatinib to the combination of trastuzumab (Herceptin) and capecitabine (Xeloda)  in patients with heavily pretreated unresectable locally advanced or metastatic HER2-positive breast cancer compared to the combination alone, according to results from the phase II HER2CLIMB trial presented at the 2019 San Antonio Breast Cancer Symposium.1,2

The median overall survival (OS) was 21.9 months (95% CI,18.3-31.0) with the tucatinib triplet compared with 17.4 months (95% CI, 13.6-19.9) with trastuzumab and capecitabine alone (HR, 0.66; 95% CI, 0.50-0.88; P = .0048). The 1- and 2-year OS rates were 76% versus 62% and 45% versus 27% in the tucatinib and control arms, respectively. The OS benefit was upheld across all prespecified subgroups. 

The addition of the small molecule TKI tucatinib also led to a 46% reduction in the risk of disease progression or death compared with trastuzumab and capecitabine alone, with a median progression-free survival (PFS) of 7.8 months (95% CI, 7.5-9.6) versus 5.6 months (95% CI, 4.2-7.1), respectively (HR, 0.54; 95% CI, 0.42-0.71; P <.00001). The 6-month and 1-year PFS rates were 63% versus 46% and 33% versus 12%, respectively. The PFS benefit was upheld across all clinically significant prespecified subgroups. 

Notably, the tucatinib triplet reduced the risk of disease progression or death by 52% (HR, 0.48; 95% CI, 0.34-0.69; P <.00001) in patients with brain metastases at baseline. The median PFS in this subpopulation with high unmet medical need was 7.6 months with tucatinib versus 5.4 months in the control arm. The 1-year PFS rates were 25% versus 0%, respectively. Subgroup analysis also indicated an OS benefit with tucatinib in this subgroup (HR, 0.58, 95% CI, 0.40-0.85).

Seattle Genetics, the manufacturer of tucatinib, plans to submit a new drug application to the FDA for tucatinib by the first quarter of 2020.

“The overall survival benefit was seen in patients who had received trastuzumab, pertuzumab, and T-DM1, and included patients who had brain metastases,” said lead study author Rashmi K. Murthy, MD, assistant professor, Department of Breast Medical Oncology, Division of Cancer Medicine, at The University of Texas MD Anderson Cancer Center.

“These study results represent at important advance toward improving outcomes for patients with HER2-positive metastatic breast cancer,” added Murthy. “Tucatinib in combination with trastuzumab and capecitabine has the potential to become a new standard of care in this population.”

The international, double-blind, placebo-controlled HER2CLIMB trial (NCT02614794) included 612 patients with unresectable locally advanced or metastatic HER2-positive breast cancer who were previously treated with trastuzumab, pertuzumab (Perjeta), and ado-trastuzumab emtansine (T-DM1; Kadcyla). Patients were randomized 2:1 to receive trastuzumab and capecitabine combined with either tucatinib (n = 410) or placebo (n = 202).

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