A 59-Year-Old Woman With HER2+ De Novo Metastatic Breast Cancer - Episode 6
Reshma L. Mahtani, DO:One of the ways that we can mitigate toxicity to neratinib is with prophylactic strategies and dose escalation. This was actually evaluated in the CONTROL trial. It evaluated the effect of prophylaxis or neratinib dose escalation on neratinib-associated diarrhea and tolerability. It was a multi-cohort study of patients who completed a year of trastuzumab, and it looked at upfront loperamide alone, or loperamide plus colestipol or budesonide. There were also 2 arms that included 2 different dose escalation strategies.
What we were able to see with initial data was that we were able to bring down the rates of grade 3 diarrhea to 31% with loperamide alone to more like 7% to 15% with dose escalation strategies. But these are early data. They’re promising, but we’re looking for updated data for the dose escalation cohorts in the future. Again, it’s something to consider. The median cumulative duration of grade 3 diarrhea across the study cohorts ranged from about 2 to 5 days for the entire 12-month treatment period. So we certainly do have strategies to mitigate the diarrhea associated with neratinib.
I would say that these are exciting times for the treatment of HER2+ metastatic breast cancer. We firmly established first- and second-line treatment algorithms with therapies that are very well tolerated and have actually extended survival. Last year, we had an important approval of a new antibody-drug conjugate, trastuzumab deruxtecan, which has shown remarkable single-agent activity in a heavily pretreated patient population. We expanded the use of the oral tyrosine kinase inhibitor neratinib from the extended adjuvant setting to the metastatic setting in combination with capecitabine.
We’re eagerly awaiting the approval of tucatinib, a drug that’s very well tolerated and has improved survival in patients with and without brain metastases. The landscape may be changing further in the next few years, as we see further data on other novel therapies, including margetuximab, an Fc-optimized chimeric monoclonal antibody optimized to increase HER2 immune targeting, as well as other novel tyrosine kinase inhibitors, including pirotinib.
There are also areas where we still need further information, such as with the use of CDK4/6 inhibitors in ER+, HER2+ breast cancer and how to incorporate immunotherapy into the treatment paradigm. Understanding mechanisms of resistance, improving therapeutic options for patients with brain metastases, and strategies in the adjuvant setting to prevent central nervous system relapses are areas of ongoing research.
Transcript edited for clarity.
Case: A 59-Year-Old Woman WithHER2+ De Novo Metastatic Breast Cancer
Treatment and Follow-Up