Nancy Lin, MD

Nancy U. Lin, MD, associate professor of Medicine at Harvard Medical School, associate chief of the Division of Breast Oncology at the Susan F. Smith Center for Women's Cancers, and director of the Metastatic Breast Cancer Program at the Dana-Farber Cancer Institute, discusses the results from a substudy of HER2CLIMB looking at tucatinib (Tukysa) plus trastuzumab (Herceptin) and capecitabine in patients with HER2-positive breast cancer and brain metastases.

This subgroup was made up of about 300 patients who had brain metastases at baseline. Lin says the important distinction in these patients, in addition to the high proportion of the patients with brain metastases enrolled within the trial overall, is that 60% of them had active brain metastases. Most of the trials of breast cancer that included patients with brain metastases have only treated those with stable brain metastases. This study is the first registration trial of breast cancer to include patients with active brain metastases.

The results of this exploratory analysis showed this subset of patients in HER2CLIMB had a significant reduction by about two-thirds in time to central nervous system (CNS) progression or death. There was significant reduction in overall survival (OS) with a hazard ratio of 0.58, and this corresponded to a more than 6-month prolongation of median OS in this type of patient, according to Lin.

Among the subset of patients with measurable, active brain metastases at baseline, the CNS objective response rate was 47% versus 20% with trastuzumab and capecitabine alone. Lin thinks all of these data put together suggest that the triplet of tucatinib plus trastuzumab and capecitabine not only leads to response and PFS advantages for patients with brain metastases but also substantially improves OS.

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Nancy U. Lin, MD, discusses the results from a substudy of HER2CLIMB looking at tucatinib plus trastuzumab and capecitabine in patients with HER2-positive breast cancer and brain metastases.

Survival Advantage Observed in HER2+Breast Cancer With Brain Metastasis

Nancy U. Lin, MD, associate professor of medicine at Harvard Medical School; associate chief of the Division of Breast Oncology at the Susan F. Smith Center for Women's Cancers; and director of the Metastatic Breast Cancer Program at the Dana-Farber Cancer Institute, discusses how she would use the HER2CLIMB regimen of tucatinib (Tukysa) plus trastuzumab (Herceptin) and capecitabine now that it has been approved for treatment of patients with HER2-positive metastatic breast cancer.

Patients had to be in their third line of treatment to be included in the HER2CLIMB trial, and that’s where Lin says she would use it in the clinic, instead of as a later-line regimen. She would move it up because of the potential benefits, including survival. The benefit with the triplet was seen in the overall population, not just patients with brain metastases.

This combination has a learning curve in terms of managing the toxicity profile, according to Lin. The adverse events were manageable in HER2CLIMB, and a lot of the toxicity came from what has been previously seen with capecitabine.

Most patients in this setting have already been exposed to trastuzumab by the time they enroll to the HER2CLIMB regimen. There can be some diarrhea and rash with tucatinib, but these events are less common than with other tyrosine kinase inhibitors, which target 

 more strongly. Lin says there can be some increases in liver function blood tests that oncologists should monitor closely.

Overall, Lin thinks this regimen is manageable from a toxicity standpoint. The quality of life for patients while receiving this regimen can be good. There was a substudy in the HER2CLIMB trial, and those results will provide more information on how the triplet impacts patients.

Nancy U. Lin, MD, discusses how she would use the HER2CLIMB regimen of tucatinib plus trastuzumab and capecitabine now that it has been approved for treatment of patients with HER2-positive metastatic breast cancer.

HER2CLIMB Regimen Can Be Used Earlier in HER2+ Metastatic Breast Cancer

Nancy U. Lin, MD, associate professor of medicine at Harvard Medical School; associate chief of the Division of Breast Oncology at the Susan F. Smith Center for Women's Cancers; and director of the Metastatic Breast Cancer Program at the Dana-Farber Cancer Institute, discusses the latest findings from the HER2CLIMB study (NCT02614794) of either tucatinib (Tukysa) or placebo, added to trastuzumab (Herceptin) and capecitabine (Xeloda), for patients with previously treated HER2-positive metastatic breast cancer who have brain metastases.

The HER2CLIMB trial enrolled about 600 patients, of which 291 patients had brain metastases at baseline, which Lin says is a unique feature of this clinical trial. Of the 291 patients, 60% had new or active brain metastases when entering the study. She and the other investigators were looking at outcomes of patients with brain metastases enrolled on HER2CLIMB.

With the tucatinib regimen, the investigators found the intracranial response rate was higher. About half of patients on the triplet achieved a central nervous system (CNS) partial response or better compared with about 20% who received the placebo regimen. Lin says that more importantly, there was a prolongation of the CNS progression-free survival, which was defined as time from randomization to CNS progression or death. CNS progression was reduced by about two-thirds for patients receiving tucatinib, and there was a 5-month absolute improvement in median time to CNS progression or death.

There was a significant improvement in overall survival for the brain metastasis population receiving the triplet regimen. The hazard ratio for survival was 0.58, and there was an absolute improvement of about 6 months for the median overall survival with tucatinib in this difficult-to-treat patient population, according to Lin.

Nancy U. Lin, MD, discusses the latest findings from the HER2CLIMB study of either tucatinib or placebo, added to trastuzumab and capecitabine, for patients with previously treated HER2-positive metastatic breast cancer who have brain metastases.

HER2CLIMB Study Shows Efficacy in HER2 Breast Cancer With Brain Metastases

Nancy Lin, MD, an associate professor of medicine at the Dana-Farber Cancer Institute and Harvard Medical School, discusses options for patients with human epidermal growth factor receptor 2 (HER2)-positive breast cancer who also present with brain metastases.

Systemic therapies for these patients can be effective, according to Lin. She says that these systemic therpaies include a number of treatments such as neratinib (Nerlynx) plus capecitabine (Xeloda) and lapatinib (Tykerb) plus capecitabine, and tucatinib (Tukysa) plus capecitabine and trastuzumab (Herceptin). All of these therapies have demonstrated central nervous system activity. The combination of neratinib and lapatinib plus capecitabine was investigated in the phase III NALA trial, and trastuzumab was looked at in the phase II HER2CLIMB trial.

When physicians think about how to treat brain metastases in the paradigm, they don’t always have to use radiation therapy for patients with HER2-postive breast cancer and brain involvement, according to Lin. This is especially important for patients who have had prior rounds of radiation therapy because she feels it makes more sense in that situation to look at systemic approaches.

<< View more resources and information regarding HER2-positive breast cancer

Nancy Lin, MD, discusses options for patients with human epidermal growth factor receptor 2-positive breast cancer who also present with brain metastases.

Nancy Lin, MD | Authors

Articles

Survival Advantage Observed in HER2+Breast Cancer With Brain Metastasis

HER2CLIMB Regimen Can Be Used Earlier in HER2+ Metastatic Breast Cancer

HER2CLIMB Study Shows Efficacy in HER2 Breast Cancer With Brain Metastases

Systemic Therapies Shown to be Effective in HER2-Positive Breast Cancer