Targeted HER2+ Breast Cancer Medicine Approved

Adults undergoing HER2+ breast cancer treatment received some good news today.

The U.S. Food and Drug Administration (FDA) has granted approval to TUKYSA™ (tucatinib) tablets in combination with trastuzumab and capecitabine, for adult patients with advanced unresectable or metastatic HER2-positive breast cancer.

This FDA approval includes patients with brain metastases, who have received 1 or more prior anti-HER2-based regimens in the metastatic setting. 

Washington-based Seattle Genetics, Inc., said on April 20, 2020, the FDA previously granted Breakthrough Therapy designation and Priority Review for TUKYSA and reviewed this application for approval under the Real-Time Oncology Review (RTOR) pilot program. 

TUKYSA is an oral, small-molecule tyrosine kinase inhibitor (TKI) of HER2, a protein that contributes to cancer cell growth.

Patients with HER2-positive breast cancer have tumors with high levels of a protein called human epidermal growth factor receptor 2 (HER2), which promotes the growth of cancer cells. 

An estimated 279,100 new cases of breast cancer will be diagnosed in the U.S. in 2020. Between 15 and 20 percent of breast cancer cases are HER2-positive.

Historically, HER2-positive breast cancer tends to be more aggressive and more likely to recur than HER2-negative breast cancer.

Furthermore, up to 50 percent of metastatic HER2-positive breast cancer patients develop brain metastases over time.

The TUKYSA New Drug Application (NDA) is also part of Project Orbis, an initiative of the FDA Oncology Center of Excellence that provides a framework for concurrent submission and review of oncology drugs among participating international health authorities. 

Eric P. Winer, M.D., Chief of the Division of Breast Oncology, Susan F. Smith Center for Women's Cancers at Dana-Farber, said in a related press release, “Cancer spreads to the brain in up to half of patients with HER2-positive metastatic breast cancer; and this approval is based on a unique clinical trial that included patients with active brain metastases, either untreated or progressing.” 

“TUKYSA is well tolerated by patients and is a valuable addition to the agents we have for HER2-positive metastatic breast cancer.”

TUKYSA, in combination with trastuzumab and capecitabine, was evaluated in the trial HER2CLIMB, a randomized (2:1), double-blind, placebo-controlled trial that enrolled 612 patients with HER2-positive unresectable locally advanced or metastatic breast cancer who had previously received, either separately or in combination, trastuzumab, pertuzumab, and ado-trastuzumab emtansine (T-DM1). 

Forty-eight percent of patients in the study had a presence or history of brain metastases. 

The primary efficacy outcome measure was progression-free survival (PFS) as assessed by blinded independent central review (BICR) in the first 480 randomized patients.

Additional efficacy outcome measures were evaluated in all randomized patients and included overall survival (OS), PFS in patients with a history or presence of brain metastases, and confirmed objective response rate (ORR).

Patients who received TUKYSA in combination with trastuzumab and capecitabine had a 46 percent reduction in the risk of cancer progression or death (PFS) compared to patients who received trastuzumab and capecitabine alone (hazard ratio (HR)=0.54 [95% Confidence Interval (CI): 0.42, 0.71]; p<0.00001). 

The addition of TUKYSA reduced the risk of death (OS) by 34 percent compared to trastuzumab and capecitabine alone (HR=0.66 [95% CI: 0.50, 0.87]; p=0.0048). 

Nearly twice the number of patients who received TUKYSA in combination with trastuzumab and capecitabine had a confirmed objective response compared to those who received trastuzumab and capecitabine alone (40.6 percent (95% CI: 35.3, 46.0) vs. 22.8 percent (95% CI: 16.7, 29.8); p=0.00008). 

For patients with brain metastases, the addition of TUKYSA reduced the risk of cancer progression or death (PFS) by 52 percent compared to trastuzumab and capecitabine alone (HR=0.48 [95% CI: 0.34, 0.69]; p<0.00001).

Serious adverse reactions occurred in 26 percent of patients who received TUKYSA. 

For more information, please see the full Prescribing Information for TUKYSA.

Seattle Genetics, Inc. is a global biotechnology company that discovers, develops and commercializes transformative medicines targeting cancer to make a meaningful difference in people’s lives. The company is headquartered in Bothell, Washington, and has offices in California, Switzerland and the European Union. 

HER-2 breast cancer treatment news published by Vax-Before-Cancer.