Pathologic Complete Response to Neoadjuvant Therapy Associated With Improved Outcomes in HER2-Positive Breast Cancer
Pathologic complete response to neoadjuvant therapy in HER2-positive breast cancer was associated with a significantly better outcome vs non–pathologic complete response, in a patient-level meta-analysis reported by Broglio et al in JAMA Oncology.
Response vs No Response
The study included patient-level data from 5,768 patients with stages I to III HER2-positive breast cancer from 36 cohort or randomized studies. A significant improvement in event-free survival was observed for pathologic complete response vs non–pathologic complete response (hazard ratio [HR] = 0.37, 95% probability interval [PI] = 0.32–0.43), with the association being greater in hormone receptor–negative disease (HR = 0.29, 95% PI = 0.24–0.36) than in hormone receptor–positive disease (HR = 0.52, 95% PI = 0.40–0.66). Pathologic complete response was associated with a significant improvement in overall survival (HR = 0.34, 95% PI = 0.26–0.42).
The effect of pathologic complete response was greater for neoadjuvant anti-HER2 therapy (HR = 0.35, 95% PI = 0.30–0.40) than for no neoadjuvant anti-HER2 therapy (HR = 0.45, 95% PI = 0.35–0.57); it was somewhat greater in cohort studies (HR = 0.33, 95% PI = 0.27–0.41) than in randomized trials (HR = 0.40, 95% CI = 0.33–0.49).
Trial-Level Analysis
Analysis of randomized controlled trials showed that R2 correlations between odds ratios for pathologic complete response and hazard ratios were 0.63 for event-free survival and 0.29 for overall survival. Based on absolute treatment improvements associated with pathologic complete response rate, the predicted hazard ratios for event-free survival for randomized trials were concordant with observed hazard ratios.
The investigators concluded: “Pathologic complete response in HER2-positive breast cancer is associated with substantially longer times to recurrence and death. This relationship is maintained in [randomized controlled trials]. For any particular new therapy the relationship between [pathologic complete response] and survival may differ. Quantifying the importance of [pathologic complete response] is necessary for designing efficient clinical trials, which should adapt to the relationship between [pathologic complete response] and survival for the therapy under investigation.”
The study was supported by Roche Canada.
Donald A. Berry, PhD, of Berry Consultants, LLC, Austin, is the corresponding author of the JAMA Oncology article.
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