publication date: Jul. 11, 2014

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By Donald Berry

An article in the June 6 issue of The Cancer Letter described plenary presentations at ASCO 2014. One presentation was the adjuvant breast cancer clinical trial ALTTO in HER2-positive disease, which “was chosen [for the plenary session] because it addressed the reliability of pathological complete response as a surrogate for patient benefit.” The article and much ASCO and post-ASCO rhetoric in the breast cancer community focused on the conclusion that ALTTO failed to show a statistically significant benefit in disease-free survival (DFS) for combination lapatinib/trastuzumab in comparison with trastuzumab, both on a backbone of chemotherapy. This was despite a statistically significant benefit in pathological complete response (pCR) in NeoALTTO, the neoadjuvant version of ALTTO.

Statistical significance in one trial on one endpoint does not imply statistical significance in another trial on another endpoint. Moreover, lack of significance in the second trial is irrelevant as regards the predictability of the latter endpoint from the former. Contrary to the rhetoric, the best available and generally accepted evidence regarding the relationship between DFS and pCR actually perfectly predicts ALTTO from NeoALTTO.

The best available evidence is the FDA-led meta-analysis showing the relationship between pCR and EFS (event-free survival, the FDA’s version of DFS). This meta-analysis was presented at the 2012 San Antonio Breast Cancer Symposium and published by Cortazar, et al. in Lancet, 2014. It showed that the EFS hazard ratio of achieving a pCR as opposed to less than a complete response in HER2-positive breast cancer was 0.39 (95% confidence interval 0.31-0.50).

This … Continue reading 40-28 Don Berry: In NeoALTTO & ALTTO Trials, Neoadjuvant Response Predicts Adjuvant

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