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Top Line: Do women with triple-positive breast cancer (TPBC) benefit from incorporation of CDK-4/6 inhibitors?

The Study: This is a nuanced question. There are a number of combinations of endocrine therapy, cytotoxic chemotherapy, and HER2-targeted therapy for this population. The problem is deciding how to approach treatment resistance after progression through several lines of therapy. In addition to the benefits seen in hormone receptor-positive patients, it’s hypothesized that CDK 4/6 inhibition might re-sensitize tumors to HER2-targeted therapy. In the three-arm, randomized phase 2 monarcHER trial, women with TPBC and receipt of at least two prior HER2-targeted agents received trastuzumab in addition to [1] chemo, [2] abemaciclib, or [3] abemaciclib + fulvestrant. Because, again, who really knows what the heck to do here? The primary goal was to determine if the non-chemo triplet regimen (arm 3) improved progression-free survival (PFS) compared to chemo and, second, to determine if the non-chemo doublet (arm 2) improved PFS compared to chemo. There did appear to be a benefit in the triplet arm with a median PFS of 8.3 months vs. 5.7 months with chemo. There was no difference in PFS, though, without fulvestrant. The non-chemo triplet also achieved a doubling in response rate,...and in grade 3+ toxicity.

TBL: The combination of abemaciclib, fulvestrant, and trastuzumab may be a promising non-chemo treatment option in women with progressive TPBC after multiple lines of therapy. | Tolaney, Lancet Oncol 2020