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SAN ANTONIO – Tucatinib, an investigational oral inhibitor of human epidermal growth factor receptor 2 (HER2) tyrosine kinase, constitutes a major advance in the treatment of heavily pretreated HER2-positive metastatic breast cancer – including patients with brain metastases, Rashmi K. Murthy, MD, declared at the San Antonio Breast Cancer Symposium.
She presented the results of the pivotal HER2CLIMB trial, in which 612 women with heavily pretreated HER2-positive metastatic breast cancer were randomized two-to-one to oral tucatinib at 300 mg twice daily or placebo in combination with standard guideline-recommended treatment with trastuzumab and capecitabine. This landmark double-blind study, conducted at 155 sites in 15 countries, was the first-ever randomized trial to include HER2-positive metastatic breast cancer patients with baseline untreated or previously treated but progressing brain metastases; indeed, nearly half of participants had baseline brain metastases, 40% of which were untreated or treated and progressing.
Not only did tucatinib on top of background trastuzumab and capecitabine reduce the risk of death by 34% compared with placebo, it also more than doubled progression-free survival. And most encouragingly, it did so in patients with or without baseline brain metastases.
“I would like to take a minute here to highlight that this overall survival benefit was seen in patients who had already received trastuzumab, pertuzumab, and T-DM1 [trastuzumab emtansine] and included patients who had brain metastases. Tucatinib in combination with trastuzumab and capecitabine has the potential to become a new standard of care in this population with and without brain metastases,” said Dr. Murthy, a medical oncologist at the University of Texas MD Anderson Cancer Center, Houston.
Tucatinib, which crosses the blood-brain barrier, is highly selective for the kinase domain of HER2, with only miniscule inhibition of epidermal growth factor receptor. Its high selectivity is reflected in a favorable tolerability profile: Only 6% of patients discontinued tucatinib because of adverse events. This low discontinuation rate permitted longer treatment, even in this heavily pretreated population.
The most common adverse events in the tucatinib study arm were diarrhea, hand-foot syndrome, nausea, fatigue, and vomiting, with most cases being low grade. Diarrhea, the most common adverse event, occurred in 81% of tucatinib-treated patients and 53% of controls. However, only 13% of the tucatinib group experienced grade 3 or worse diarrhea. Notably, antidiarrheal prophylaxis wasn’t mandated in HER2CLIMB. Antidiarrheal medications were utilized in less than half of the treatment cycles where diarrhea was reported, and even then, for a median of only 3 days per cycle.
Median study follow-up was 14 months. The primary study endpoint – 1-year progression-free survival assessed by blinded independent central review – was 33% in the tucatinib group and 12% in controls. Thus, the risk of disease progression or death was reduced by 46% in the tucatinib group. The median duration of progression-free survival was 7.8 months in tucatinib-treated patients, compared with 5.6 months in controls.
Two-year estimated overall survival was 45% with tucatinib and 27% with placebo. The tucatinib group’s 21.9-month median overall survival was 4.5 months greater than in controls.
One-year estimated progression-free survival in patients with baseline brain metastases was 25% in the tucatinib group and zero in controls.
The confirmed objective response rate was 41% in the tucatinib group, nearly double the 23% figure in controls.
The overall and progression-free survival results were consistent across all prespecified subgroups based upon age, race, hormone receptor status, geographic location, and other factors.
The study met with an extremely favorable reception peppered with comments such as “tremendous results.”
“I think that the HER2CLIMB study is practice-changing,” Hope S. Rugo, MD, said in an interview.
“The overall survival benefit in all patients and in those who have brain metastases is clinically relevant for our patients who have HER2-positive metastatic breast cancer treated with trastuzumab, pertuzumab, and T-DMI. In addition, the toxicity profile is superior to prior oral TKIs, which is a huge issue for our patients with metastatic disease,” observed Dr. Rugo, professor of medicine and director of breast oncology and clinical trials education at the University of California, San Francisco.
The HER2CLIMB results raise an important question for future research: Namely, could tucatinib have a role in preventing brain metastases by giving the drug earlier in the course of treatment of patients who are at high risk for developing brain metastases, she added.
Simultaneously with Dr. Murthy’s presentation in San Antonio, the HER2CLIMB results were published online in the New England Journal of Medicine.
Dr. Murthy reported receiving institutional research support from and serving as a consultant to Seattle Genetics, sponsor of the HER2CLIMB trial, as well as from several other pharmaceutical companies.
SOURCE: Murthy RK. SABCS 2019 Abstract GS1-01.
SAN ANTONIO – Tucatinib, an investigational oral inhibitor of human epidermal growth factor receptor 2 (HER2) tyrosine kinase, constitutes a major advance in the treatment of heavily pretreated HER2-positive metastatic breast cancer – including patients with brain metastases, Rashmi K. Murthy, MD, declared at the San Antonio Breast Cancer Symposium.
She presented the results of the pivotal HER2CLIMB trial, in which 612 women with heavily pretreated HER2-positive metastatic breast cancer were randomized two-to-one to oral tucatinib at 300 mg twice daily or placebo in combination with standard guideline-recommended treatment with trastuzumab and capecitabine. This landmark double-blind study, conducted at 155 sites in 15 countries, was the first-ever randomized trial to include HER2-positive metastatic breast cancer patients with baseline untreated or previously treated but progressing brain metastases; indeed, nearly half of participants had baseline brain metastases, 40% of which were untreated or treated and progressing.
Not only did tucatinib on top of background trastuzumab and capecitabine reduce the risk of death by 34% compared with placebo, it also more than doubled progression-free survival. And most encouragingly, it did so in patients with or without baseline brain metastases.
“I would like to take a minute here to highlight that this overall survival benefit was seen in patients who had already received trastuzumab, pertuzumab, and T-DM1 [trastuzumab emtansine] and included patients who had brain metastases. Tucatinib in combination with trastuzumab and capecitabine has the potential to become a new standard of care in this population with and without brain metastases,” said Dr. Murthy, a medical oncologist at the University of Texas MD Anderson Cancer Center, Houston.
Tucatinib, which crosses the blood-brain barrier, is highly selective for the kinase domain of HER2, with only miniscule inhibition of epidermal growth factor receptor. Its high selectivity is reflected in a favorable tolerability profile: Only 6% of patients discontinued tucatinib because of adverse events. This low discontinuation rate permitted longer treatment, even in this heavily pretreated population.
The most common adverse events in the tucatinib study arm were diarrhea, hand-foot syndrome, nausea, fatigue, and vomiting, with most cases being low grade. Diarrhea, the most common adverse event, occurred in 81% of tucatinib-treated patients and 53% of controls. However, only 13% of the tucatinib group experienced grade 3 or worse diarrhea. Notably, antidiarrheal prophylaxis wasn’t mandated in HER2CLIMB. Antidiarrheal medications were utilized in less than half of the treatment cycles where diarrhea was reported, and even then, for a median of only 3 days per cycle.
Median study follow-up was 14 months. The primary study endpoint – 1-year progression-free survival assessed by blinded independent central review – was 33% in the tucatinib group and 12% in controls. Thus, the risk of disease progression or death was reduced by 46% in the tucatinib group. The median duration of progression-free survival was 7.8 months in tucatinib-treated patients, compared with 5.6 months in controls.
Two-year estimated overall survival was 45% with tucatinib and 27% with placebo. The tucatinib group’s 21.9-month median overall survival was 4.5 months greater than in controls.
One-year estimated progression-free survival in patients with baseline brain metastases was 25% in the tucatinib group and zero in controls.
The confirmed objective response rate was 41% in the tucatinib group, nearly double the 23% figure in controls.
The overall and progression-free survival results were consistent across all prespecified subgroups based upon age, race, hormone receptor status, geographic location, and other factors.
The study met with an extremely favorable reception peppered with comments such as “tremendous results.”
“I think that the HER2CLIMB study is practice-changing,” Hope S. Rugo, MD, said in an interview.
“The overall survival benefit in all patients and in those who have brain metastases is clinically relevant for our patients who have HER2-positive metastatic breast cancer treated with trastuzumab, pertuzumab, and T-DMI. In addition, the toxicity profile is superior to prior oral TKIs, which is a huge issue for our patients with metastatic disease,” observed Dr. Rugo, professor of medicine and director of breast oncology and clinical trials education at the University of California, San Francisco.
The HER2CLIMB results raise an important question for future research: Namely, could tucatinib have a role in preventing brain metastases by giving the drug earlier in the course of treatment of patients who are at high risk for developing brain metastases, she added.
Simultaneously with Dr. Murthy’s presentation in San Antonio, the HER2CLIMB results were published online in the New England Journal of Medicine.
Dr. Murthy reported receiving institutional research support from and serving as a consultant to Seattle Genetics, sponsor of the HER2CLIMB trial, as well as from several other pharmaceutical companies.
SOURCE: Murthy RK. SABCS 2019 Abstract GS1-01.
SAN ANTONIO – Tucatinib, an investigational oral inhibitor of human epidermal growth factor receptor 2 (HER2) tyrosine kinase, constitutes a major advance in the treatment of heavily pretreated HER2-positive metastatic breast cancer – including patients with brain metastases, Rashmi K. Murthy, MD, declared at the San Antonio Breast Cancer Symposium.
She presented the results of the pivotal HER2CLIMB trial, in which 612 women with heavily pretreated HER2-positive metastatic breast cancer were randomized two-to-one to oral tucatinib at 300 mg twice daily or placebo in combination with standard guideline-recommended treatment with trastuzumab and capecitabine. This landmark double-blind study, conducted at 155 sites in 15 countries, was the first-ever randomized trial to include HER2-positive metastatic breast cancer patients with baseline untreated or previously treated but progressing brain metastases; indeed, nearly half of participants had baseline brain metastases, 40% of which were untreated or treated and progressing.
Not only did tucatinib on top of background trastuzumab and capecitabine reduce the risk of death by 34% compared with placebo, it also more than doubled progression-free survival. And most encouragingly, it did so in patients with or without baseline brain metastases.
“I would like to take a minute here to highlight that this overall survival benefit was seen in patients who had already received trastuzumab, pertuzumab, and T-DM1 [trastuzumab emtansine] and included patients who had brain metastases. Tucatinib in combination with trastuzumab and capecitabine has the potential to become a new standard of care in this population with and without brain metastases,” said Dr. Murthy, a medical oncologist at the University of Texas MD Anderson Cancer Center, Houston.
Tucatinib, which crosses the blood-brain barrier, is highly selective for the kinase domain of HER2, with only miniscule inhibition of epidermal growth factor receptor. Its high selectivity is reflected in a favorable tolerability profile: Only 6% of patients discontinued tucatinib because of adverse events. This low discontinuation rate permitted longer treatment, even in this heavily pretreated population.
The most common adverse events in the tucatinib study arm were diarrhea, hand-foot syndrome, nausea, fatigue, and vomiting, with most cases being low grade. Diarrhea, the most common adverse event, occurred in 81% of tucatinib-treated patients and 53% of controls. However, only 13% of the tucatinib group experienced grade 3 or worse diarrhea. Notably, antidiarrheal prophylaxis wasn’t mandated in HER2CLIMB. Antidiarrheal medications were utilized in less than half of the treatment cycles where diarrhea was reported, and even then, for a median of only 3 days per cycle.
Median study follow-up was 14 months. The primary study endpoint – 1-year progression-free survival assessed by blinded independent central review – was 33% in the tucatinib group and 12% in controls. Thus, the risk of disease progression or death was reduced by 46% in the tucatinib group. The median duration of progression-free survival was 7.8 months in tucatinib-treated patients, compared with 5.6 months in controls.
Two-year estimated overall survival was 45% with tucatinib and 27% with placebo. The tucatinib group’s 21.9-month median overall survival was 4.5 months greater than in controls.
One-year estimated progression-free survival in patients with baseline brain metastases was 25% in the tucatinib group and zero in controls.
The confirmed objective response rate was 41% in the tucatinib group, nearly double the 23% figure in controls.
The overall and progression-free survival results were consistent across all prespecified subgroups based upon age, race, hormone receptor status, geographic location, and other factors.
The study met with an extremely favorable reception peppered with comments such as “tremendous results.”
“I think that the HER2CLIMB study is practice-changing,” Hope S. Rugo, MD, said in an interview.
“The overall survival benefit in all patients and in those who have brain metastases is clinically relevant for our patients who have HER2-positive metastatic breast cancer treated with trastuzumab, pertuzumab, and T-DMI. In addition, the toxicity profile is superior to prior oral TKIs, which is a huge issue for our patients with metastatic disease,” observed Dr. Rugo, professor of medicine and director of breast oncology and clinical trials education at the University of California, San Francisco.
The HER2CLIMB results raise an important question for future research: Namely, could tucatinib have a role in preventing brain metastases by giving the drug earlier in the course of treatment of patients who are at high risk for developing brain metastases, she added.
Simultaneously with Dr. Murthy’s presentation in San Antonio, the HER2CLIMB results were published online in the New England Journal of Medicine.
Dr. Murthy reported receiving institutional research support from and serving as a consultant to Seattle Genetics, sponsor of the HER2CLIMB trial, as well as from several other pharmaceutical companies.
SOURCE: Murthy RK. SABCS 2019 Abstract GS1-01.
REPORTING FROM SABCS 2019