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Top Line: While some women with early-stage, ER(+) positive breast cancer receive cytotoxic chemo, those with metastatic disease receive endocrine therapy and CDK 4/6 inhibitors.
The Study: That just doesn’t seem right. CORALEEN was a randomized phase 2 trial where post-menopausal women with locoregional, ER/PR(+), HER2(-) breast cancer received either neoadjuvant chemo (AC→ T) or letrozole and ribociclib for 6 months. Now, central to this study was the PAM50 molecular profiling test used to assign molecular subtypes, and all enrollees had to have luminal B breast cancer. The PAM50 test also generates a risk of recurrence (ROR) score that estimates the risk of distant recurrence at 10 years without chemotherapy. None of the enrolled patients had a low ROR at enrollment, and roughly 85% had a high ROR. Here’s where things get really novel. The primary outcome was the proportion of patients converted to a low ROR after neoadjuvant therapy. This can be considered “molecular down-staging” as opposed to pathologic down-staging, which is a known challenge seen in ER/PR+ breast cancer. At surgery, nearly half (46%) of patients in each group were molecularly down-staged to a low ROR score, while 21-22% still had high ROR. In other words, a similar rate of molecular down-staging was achieved with a chemo-free targeted therapy regimen with less toxicity. As you can see, the ultimate challenge in unseating chemotherapy for early-stage disease is establishing surrogate outcomes that are both meaningful and feasibly measured in clinical trials.
TBL: Neoadjuvant letrozole and ribociclib achieve similar rates of “molecular down-staging” as cytotoxic chemo for women with luminal B type breast cancer. | Prat, Lancet Oncol 2019