A chemo COX block.
Top Line: We’ve know for a while now that the Y2K fad of celecoxib with cancer treatment wasn’t all we dreamed it would be.
The Study: The rationale behind it was that many cancers over-express COX-2. So why didn’t a COX-2 inhibitor help? REMAGUS02 was one of these early trials that randomized women with advanced breast cancer receiving neoadjuvant epirubicin and cyclophosphamide to sequential docetaxel +/- celecoxib. In the original report, celecoxib failed to improve the pathologic complete response rate. A decade later, we have an exploratory analysis of event-free survival (EFS) correlated with levels of COX-2 expression. Overall, celecoxib was associated with significantly worse EFS. And COX-2 expression was an important predictor of outcome, but not like you’d expect. Among women with high COX-2 expression, there was no effect. But among women with low COX-2 expression, there was a significant decrease in both EFS and overall survival with celecoxib. In particular, this was driven by detrimental effects among ER(-) tumors. The authors went a step further and investigated these effects in cell lines. Interestingly, celecoxib alone had no real effects on cell viability. Weirdly, though, when combined with docetaxel, celecoxib enhanced cell survival with low COX-2 expression.
Bottom Line: Celecoxib appears to enhance cancer survival and reduce patient survival when given with taxanes, particularly among women with ER-negative tumors and low COX-2 expression. | Hamy, J Clin Oncol 2019
The Study: The rationale behind it was that many cancers over-express COX-2. So why didn’t a COX-2 inhibitor help? REMAGUS02 was one of these early trials that randomized women with advanced breast cancer receiving neoadjuvant epirubicin and cyclophosphamide to sequential docetaxel +/- celecoxib. In the original report, celecoxib failed to improve the pathologic complete response rate. A decade later, we have an exploratory analysis of event-free survival (EFS) correlated with levels of COX-2 expression. Overall, celecoxib was associated with significantly worse EFS. And COX-2 expression was an important predictor of outcome, but not like you’d expect. Among women with high COX-2 expression, there was no effect. But among women with low COX-2 expression, there was a significant decrease in both EFS and overall survival with celecoxib. In particular, this was driven by detrimental effects among ER(-) tumors. The authors went a step further and investigated these effects in cell lines. Interestingly, celecoxib alone had no real effects on cell viability. Weirdly, though, when combined with docetaxel, celecoxib enhanced cell survival with low COX-2 expression.
Bottom Line: Celecoxib appears to enhance cancer survival and reduce patient survival when given with taxanes, particularly among women with ER-negative tumors and low COX-2 expression. | Hamy, J Clin Oncol 2019
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