TTC Safety in HER2+ Metastatic Breast Cancer: Key Findings

By: Jessica Nye, Ph

From: oncologynurseadvisor.com

n a safety review of the HER2CLIMB trial, grade 3 or higher AEs occurred in 55.2% of patients receiving TTC compared with 48.7% receiving placebo, with diarrhea being the primary AE requiring dose modifications.

A detailed safety assessment of the combination of tucatinib with trastuzumab and capecitabine (TTC) was published in The Oncologist.

The United States Food and Drug Administration (FDA) approved TTC in 2020 for the treatment of HER2+ metastatic breast cancer (mBC). Currently, TTC is preferred in the third-line setting in HER2+ mBC or second-line setting with brain metastases.

This study was a safety review of TTC using data from the HER2CLIMB (NCT02614794) trial. The patients were assigned to receive tucatinib or placebo in combination with trastuzumab and capecitabine.

During a median follow-up of 14.0 months, the rates of grade 3 or higher adverse events (AEs) were 55.2% and 48.7% and discontinuations of any treatment component due to AEs were 5.7% and 3.0% in the tucatinib and placebo study arms, respectively.

The most frequently discontinued, withheld, or reduced medication was capecitabine. The most frequent adverse event leading to TTC modifications was diarrhea. The study investigators emphasized the importance of early counseling on how to mitigate diarrhea for patients receiving TTC, including assessing dietary habits, using probiotics, and using antidiarrheals.

The rate of elevated liver enzymes was higher in the tucatinib study arm (18.6% to 21.3%) than in the placebo study arm (6.6% to 11.2%). The study investigators highlighted that both tucatinib and capecitabine have liver-related warnings for hepatotoxicity and hyperbilirubinemia, respectively. Hepatic AEs were generally manageable and reversible in HER2CLIMB.

Additional AEs of special interest associated with TTC included palmar-plantar erythrodysesthesia, elevated serum creatinine, interstitial lung disease, decreased left ventricular ejection fraction, and alopecia.

The study investigators concluded, “Proactive communication between [health care providers] and patients and prompt clinical management of the AEs most frequently requiring dose modification of the TTC regimen may help to reduce their incidence, duration, and severity, allowing for patients to continue their anticancer treatment as long as they continue to benefit.”