R/R Metastatic HER2+ Breast Cancer Treatment Considerations

Giuseppe Curigliano, MD, PhD: In the context of the real world, tucatinib is a very well-tolerated agent. I had several patients on treatment, most with brain metastases, and I believe we can balance efficacy and safety with a very good safety profile and confirmation of the PFS [progression-free survival] and overall survival benefit observed in clinical study.

You should immediately recognize the adverse events that patients report. You should avoid a deteriorating condition from the patients. If they have diarrhea, you should educate the patient to increase awareness related to potential adverse events and intervene as soon as possible. This will permit you to increase compliance to treatment and avoid treatment discontinuation or dose reduction.

The sequence of treatments should be based on current treatment guidelines, which are based on the level of evidence of prospective randomized trials. In my personal experience, the factors that have the biggest impact are the level of evidence and the grade of recommendation. If you have a prospective randomized trial, you should take into account the magnitude of benefit shown. Trials that rate the benefit of overall survival and progression-free survival should be considered for your treatment selection.

If you also have an analysis of CNS [central nervous system] metastases in which benefit is demonstrated, you should take this into account in order to treat. This is what I do in the real world. Sometimes you can deviate from guidelines. If you have a patient with dramatic visceral involvement and you’d also like to have a rapid response independently of the overall survival benefit, you can deviate from guidelines and potentially consider another agent. But as I said before, level of evidence and grade of recommendation should guide your treatment selection.

You should use the [European Society for Medical Oncology]–Magnitude of Clinical Benefit Scale when you’re balancing the efficacy and safety of various treatment options. If you have an agent at which there can be a specific toxicity, but you have an overall survival benefit, you should consider the Magnitude of Clinical Benefit score to balance efficacy and safety. I’d pay some toxicity in order to have a benefit in terms of overall survival.

I would select this treatment option for any patient progressing on pertuzumab, trastuzumab, and taxane and progressing on T-DM1 [trastuzumab emtansine], because according to the data of the HER2CLIMB study, you have clear benefit in overall survival and progression-free survival. For the very few patients without brain metastases and with basic visceral involvement, I’d use trastuzumab deruxtecan.

Transcript edited for clarity.