Updates in Metastatic HER2 Positive Breast Cancer Treatment - Episode 5
Data from the HER2CLIMB, NALA, and SOPHIA trials that led to the FDA approval of respective agents in the setting of HER2+ metastatic breast cancer.
Cynthia Lynch, MD: Other agents that have recently come available based on trials is used of tucatinib and oral tyrosine kinase in combination with trastuzumab and capecitabine. That was based on the HER2Climb trial; it was a randomized double-blind trial in individuals with metastatic HER2+ breast cancer who had previously progressed on prior therapies including trastuzumab and taxane-based therapy as well as T-DM1. This was unique at that time because it did allow patients who had brain metastases that were untreated as long as they were clinically stable and did not require urgent treatment to be enrolled on that clinical trial. What they found was individuals who received tucatinib, again, this was trastuzumab capecitabine+/-tucatinib, the risk of progression or death was reduced by 46%, the risk of death was reduced by 34%, and the risk of progression or death in patients with brain metastases was reduced by 52%. The progression-free survival at 1 year was higher with the use of tucatinib at 20% and overall survival at 2 years was higher at 18%. The main side effects when you think of adverse drug effects associated with the tucatinib arm were similar to the ones that you would see in individuals who are receiving capecitabine; diarrhea, hand-foot syndrome, nausea, and fatigue. The next trial I was going to mention is the NALA trial which was a randomized phase 3 trial evaluating the use of neratinib, a tyrosine kinase inhibitor, in combination with capecitabine versus lapatinib in combination with capecitabine in patients who had HER2+ metastatic breast cancer. What that trial demonstrated was that there was a significant improvement in progression-free survival, and that was when you looked at 6 and 12 months progression-free survival, the rates were 47% versus 37%, and in the 12 months was 28% versus 14%. Also, there was a trend towards overall survival. At 6 months, that was 90% versus 87% and at 12 months, that was 72% versus 66%. The next trial I'm going to talk about is the SOPHIA trial, which is a phase 3 trial that looked at the combination of margetuximab in combination with chemotherapy versus trastuzumab in combination with chemotherapy. The chemotherapy that was utilized was based on the selection of the oncologist. There were several options: eribulin, gemcitabine, vinorelbine, and capecitabine were options for combination for those. With that, the patients were required to have at least 2 prior lines of anti-HER2-directed therapy for that clinical trial. The results of that trial showed that was patients who received a combination of margetuximab in combination with chemotherapy did show improvement in progression-free survival; when you looked at the safety of that use of that monoclonal antibody was comparable to trastuzumab.
Transcript edited for clarity.