HER2 Support Group Forums - View Single Post - FDA approves tucatinib for Stage 4 her2+ breast cancer

Lani · 04-29-2020, 06:59 PM

Cancer
CancerScope Free Access
Addition of tucatinib to trastuzumab and chemotherapy improves survival for patients with metastatic, HER2‐positive breast cancer
Carrie Printz
First published: 28 April 2020 https://doi-

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Recent findings published in The New England Journal of Medicine have indicated that the addition of tucatinib to capecitabine and trastuzumab significantly improved progression‐free survival and overall survival in patients with advanced HER2‐positive breast cancer, regardless of whether they had metastatic disease.1 The results, from the HER2CLIMB study, were presented simultaneously at the 2019 San Antonio Breast Cancer Symposium, held December 10 to 14, 2019, in San Antonio, Texas. Tucatinib is a tyrosine kinase inhibitor (TKI) that is highly selective for HER2.

The international randomized trial enrolled 612 patients with locally advanced or metastatic HER2‐positive breast cancer who had received prior treatment with trastuzumab, pertuzumab, and trastuzumab emtansine. The patients were randomly assigned 2:1 to trastuzumab and capecitabine with or without tucatinib. Approximately one‐half of the patients (47%) had brain metastases at baseline.

Lead author Rashmi Murthy, MD, an assistant professor in the Department of Breast Medical Oncology at The University of Texas MD Anderson Cancer Center in Houston, Texas, notes that the trial allowed patients to enroll if they had untreated, treated but stable, or previously treated progressive brain metastases, the latter of which is a common clinical problem for up to one‐half of patients with the disease. She adds that these patients have limited treatment options because the majority of drugs have trouble crossing the blood‐brain barrier.

The study met its primary endpoint and demonstrated that the combination treatment reduced the risk of death by approximately 46% compared with trastuzumab and capecitabine alone. Meeting its secondary endpoints at interim analysis, the trial also showed that adding tucatinib to standard treatment prolonged overall survival, reducing the risk of death by approximately 34% and extending progression‐free survival by 52% in patients with brain metastases. Also, in the tucatinib group, the overall response rate was found to be higher at 41% compared with 23% in the standard‐of‐care treatment group.

The 3‐drug combination had no unexpected toxicities. The most common side effects with tucatinib included diarrhea, fatigue, and vomiting, the majority of which were low grade. The drug discontinuation rate was considered low, at 5.7% in the triplet arm compared with 3% in the standard‐of‐care arm.

The results demonstrate that tucatinib is both safe and effective, according to Dr. Murthy. Furthermore, they indicate that the 3‐drug combination should be the new standard of care for patients who have been pretreated with multiple anti‐HER2 agents, including those individuals with brain metastases. The findings also resulted in unblinding the study so that all patients could receive the new combination treatment. Researchers also planned to submit a new drug application to the US Food and Drug Administration early this year.

04-29-2020, 06:59 PM	#2
Lani Senior Member Join Date: Mar 2006 Posts: 4,778	Re: FDA approves tucatinib for Stage 4 her2+ breast cancer Cancer CancerScope Free Access Addition of tucatinib to trastuzumab and chemotherapy improves survival for patients with metastatic, HER2‐positive breast cancer Carrie Printz First published: 28 April 2020 https://doi- E Recent findings published in The New England Journal of Medicine have indicated that the addition of tucatinib to capecitabine and trastuzumab significantly improved progression‐free survival and overall survival in patients with advanced HER2‐positive breast cancer, regardless of whether they had metastatic disease.1 The results, from the HER2CLIMB study, were presented simultaneously at the 2019 San Antonio Breast Cancer Symposium, held December 10 to 14, 2019, in San Antonio, Texas. Tucatinib is a tyrosine kinase inhibitor (TKI) that is highly selective for HER2. The international randomized trial enrolled 612 patients with locally advanced or metastatic HER2‐positive breast cancer who had received prior treatment with trastuzumab, pertuzumab, and trastuzumab emtansine. The patients were randomly assigned 2:1 to trastuzumab and capecitabine with or without tucatinib. Approximately one‐half of the patients (47%) had brain metastases at baseline. Lead author Rashmi Murthy, MD, an assistant professor in the Department of Breast Medical Oncology at The University of Texas MD Anderson Cancer Center in Houston, Texas, notes that the trial allowed patients to enroll if they had untreated, treated but stable, or previously treated progressive brain metastases, the latter of which is a common clinical problem for up to one‐half of patients with the disease. She adds that these patients have limited treatment options because the majority of drugs have trouble crossing the blood‐brain barrier. The study met its primary endpoint and demonstrated that the combination treatment reduced the risk of death by approximately 46% compared with trastuzumab and capecitabine alone. Meeting its secondary endpoints at interim analysis, the trial also showed that adding tucatinib to standard treatment prolonged overall survival, reducing the risk of death by approximately 34% and extending progression‐free survival by 52% in patients with brain metastases. Also, in the tucatinib group, the overall response rate was found to be higher at 41% compared with 23% in the standard‐of‐care treatment group. The 3‐drug combination had no unexpected toxicities. The most common side effects with tucatinib included diarrhea, fatigue, and vomiting, the majority of which were low grade. The drug discontinuation rate was considered low, at 5.7% in the triplet arm compared with 3% in the standard‐of‐care arm. The results demonstrate that tucatinib is both safe and effective, according to Dr. Murthy. Furthermore, they indicate that the 3‐drug combination should be the new standard of care for patients who have been pretreated with multiple anti‐HER2 agents, including those individuals with brain metastases. The findings also resulted in unblinding the study so that all patients could receive the new combination treatment. Researchers also planned to submit a new drug application to the US Food and Drug Administration early this year.