Would you combine fam-trastuzumab deruxtecan with endocrine therapy? Results of Phase IB DESTINY-Breast08 trial was promising. I have a 56 yo with metastatic HR+, HER2 low breast cancer who progressed on first line endocrine therapy with anastrozole and Verzenio. I am planning on starting her on fulvestrant and Enher2. What do you think?
I usually don't combine endocrine therapy with TDX-d, since it was used as monotherapy in Destiny-Breast04. Although I agree that 08 looked promising, and it probably wouldn't add more toxicity, especially if you continued the AI. In DB04, patients needed to have had chemotherapy in the metastatic setting. However for second-line therapy, I usually try to exhaust all endocrine-based options prior to switching to chemotherapy or any ADC. For patients who progress on frontline AI+CDK, I will obtain liquid biopsy to assess for PIK3CA, PTEN/AKT1, or ESR1 mutations. If PIK3CA: alpelisib + fulvestrant (or capivasertib + fulvestrant) If PTEN/AKT: capivasertib + fulvestrant If ESR1: elacestrant If no actionable mutations: everolimus with either exemestane or fulvestrant After progression on these second-line regimens, will often do capecitabine and then finally use TDX-d for Her2-low disease.
