Top Line: Anti-angiogenic agents play an important role In advanced colorectal cancer, so maybe they can help improve pathologic complete response (pCR) rates after total neoadjuvant therapy (TNT).
The Study: With TNT, patients with high risk rectal cancer may have a better chance of receiving all their planned chemo before chemoradiation and surgery. As a bonus, all that neoadjuvant treatment may allow some patients to avoid surgery as a result of complete disease response. Unfortunately, even with TNT, rates of pCR are below 20%. In the phase 2 GEMCAD 1402 trial, over 150 patients with high risk rectal cancer were randomized to TNT +/- the addition of aflibercept to the neoadjuvant mFOLFOX6 regimen. In case you’re wondering, aflibercept is an anti-angiogenic agent with much broader activity than bevacizumab. Where bevacizumab inhibits VEGF-A, aflibercept inhibits VEGF-A, VEGF-B, and placental growth factor. Adding aflibercept to TNT resulted in a “significant” improvement in pCR rate from 14 → 23%. Importantly, this wasn’t a phase 3 trial, so the statistical p-value threshold of ≤0.2 was designed to detect possible efficacy rather than prove it. While toxicity was higher with aflibercept,mainly driven by hypertension, completion of planned therapy was similar between groups.
TBL: The addition of the anti-angiogenic aflibercept to total neoadjuvant therapy for high risk rectal cancer may improve the pathologic complete response rate by 10% without compromising the planned treatment regimen. | Fernandez-Martos, JAMA Oncol 2019


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