Defining Value for the Treatment of Brain Metastases in Metastatic HER2-Positive Breast Cancer - Episode 8

Phase 2 LANDSCAPE Trial

Sarah Sammons, MD, and Kevin M. Kalinsky, MD, MS, review the phase 2 LANDSCAPE trial using lapatinib for patients with HER2+ mBC and a history of brain metastases.

Sarah Sammons, MD: The LANDSCAPE trial was a single-arm phase 2 clinical trial that treated patients with HER2 [human epidermal growth factor receptor 2]–positive metastatic breast cancer and a history of brain metastases with lapatinib, which is a HER2- and EGFR-targeted tyrosine kinase inhibitor, and capecitabine. It was a smaller trial: There were 45 patients enrolled, and 44 patients were evaluable for efficacy. The primary end point was intracranial response rate. This is 1 of the earlier trials to show intracranial efficacy of any compound in HER2-positive breast cancer, but it showed a respectable intracranial response rate of about 65% with lapatinib and capecitabine. For a long time, lapatinib and capecitabine was 1 of the only options for patients with HER2-positive brain metastasis.

Kevin M. Kalinsky, MD, MS: This is a study that was published in The Lancet that looked at giving capecitabine and lapatinib vs capecitabine alone. This was a study that led to the utilization of lapatinib and capecitabine. Historically, we used this regimen with some regularity. Some of the issues with this regimen included adverse events, like diarrhea, and skin reactions, including hand-foot syndrome, that we can see with capecitabine.

I would say that lapatinib is an agent that we have in our armamentarium, but when we see an overall survival advantage with something like tucatinib, this just highlights how efficacious tucatinib can be in the HER2CLIMB study, and one cannot argue with the fact that we see an overall survival advantage, so this has quickly moved up as the first tyrosine kinase inhibitor of choice. This is also because it has a good toxicity profile.

Something we see with lapatinib is that, first, it’s a good number of pills that patients have to take in combination with capecitabine. The main toxicity that we see with lapatinib, as well as with neratinib, is diarrhea. That’s the main adverse effect that we have to see. We can also see gastrointestinal issues with tucatinib, but the severity and rate at which we see these with lapatinib and neratinib can often limit its tolerability in patients with HER2-positive breast cancer.