Adding Tukysa to Regimen for Metastatic HER2-Positive Breast Cancer Does Not Decrease Quality of Life

Adding the targeted drug Tukysa (tucatinib) to a two-drug regimen of Herceptin (trastuzumab) and the chemotherapy Xeloda (capecitabine) for patients with HER2-positive metastatic breast cancer – including disease that has spread to the brain – did not affect quality of life, according to recent follow-up data from the HER2CLIMB study.

The findings, indicating that long courses of the three-drug regimen can be given safely, were presented by study lead author Volkmar Mueller, head of the oncology outpatient clinic at the University Medical Center Hamburg-Eppendorf in Hamburg, Germany, during the European Society for Medical Oncology Virtual 2020 Congress.

Tukysa inhibits the activity of proteins known as kinases, thereby helping to prevent the growth of cancer cells. Metastatic breast cancer is disease that has spread beyond the breast to distant parts of the body, in some cases including the brain. Breast cancer that is HER2-positive expresses high amounts of the protein human epidermal growth factor receptor 2 (HER2), which is treatable with drugs that target that protein, such as Herceptin.

Researchers embarked on the study as a follow-up to the HER2CLIMB study, which led to the Food and Drug Administration’s approval of Tukysa. The approval was based on data showing that the drug, given with Herceptin and Xeloda, lengthened life and delayed the amount of time from the start of treatment until disease progression, compared with Herceptin and Xeloda alone in patients with metastatic, HER2-positive metastatic breast cancer with or without brain metastases who had previous treatment with another anti-HER2 drug.

In terms of overall survival, the trial demonstrated that two years after the start of treatment, 45% of patients taking the three-drug regimen were alive, compared with 27% of those who took the two-drug regimen. Average length of life from the start of treatment was 21.9 months in the triplet group versus 17.4 months in the doublet group.

The study also found that, in patients with HER2-positive metastatic breast cancer with or without spread to the brain, the triplet combination had a manageable safety profile similar to that of the Herceptin/ Xeloda pairing. Adding Tukysa to the regimen did not increase the percentage of patients requiring hospitalization, Mueller reported.

The researchers conducted the follow-up because patients with HER2-positive metastatic breast cancer, particularly those with brain metastases, have limited treatment options and an increased likelihood of reporting deterioration in their health-related quality of life. Disease progression, the scientists noted, is one factor that can negatively impact quality of life. Yet, the researchers wrote, maintaining quality of life in these patients is a key goal of treatment. Hence, the team wanted to explore the impact of the more effective triplet combination on health-related quality of life, which was a secondary goal of HER2CLIMB.

Patients included in the follow-up had HER2-positive metastatic breast cancer and had received previous treatment with three anti-HER2 drugs: Herceptin, Perjeta (pertuzumab) and Kadcyla (ado-trastuzumab emtansine). Nearly half (48%) had brain metastases at baseline.

To assess health-related quality of life, the researchers administered a questionnaire to 331 HER2CLIMB participants that evaluated their status in five areas: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. The patients were asked to rate the severity of the problems they encountered in each category as none, slight, moderate, severe or extreme. Patients filled out the surveys periodically throughout their treatment, which in some cases lasted more than six months and tended to be longer in patients receiving the drug triplet; they were questioned again 30 days after therapy had been completed. Among respondents, 218 received the triplet therapy and 113 received Herceptin plus Xeloda alone.

In all five domains, most patients in both treatment groups reported slight or no problems. Moderate, severe or extreme problems were reported infrequently and in similar numbers in each treatment group. No clinically meaningful differences in health-related quality of life were observed between the two treatment groups. Mean questionnaire scores were similar between the groups and stable throughout therapy. No decline in the domains or questionnaire scores was seen while patients were receiving therapy.

“These results, together with the HER2CLIMB primary analysis, demonstrate that this regimen not only provides significant and clinically meaningful activity, but also maintains quality of life in patients with and without brain metastases,” Mueller said.

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