Evaluation of pathologic complete response as a surrogate for long-term survival outcomes in triple-negative breast cancer

Abstract

Background: Pathologic complete response (PCR) is a common efficacy endpoint in neoadjuvant therapy trials for triple-negative breast cancer (TNBC). Previous studies have shown that PCR is strongly associated with improved long-term survival outcomes, including eventfree survival (EFS) and overall survival (OS). However, the trial-level associations between treatment effect on PCR and long-term survival outcomes are not well established. This study sought to evaluate these associations by incorporating more recent clinical trials in TNBC. Methods: A literature review identified published randomized controlled trials (RCTs) of neoadjuvant therapy for TNBC that reported results for both PCR and EFS/OS. Meta-regression models were performed to evaluate the association of treatment effect on PCR and EFS/ OS. Sensitivity analyses were conducted to assess the impact of divergent study designs. Results: Ten comparisons from 8 RCTs (N52,478 patients) were identified from the literature review. The log (odds ratio) of PCR was a significant predictor of the log (hazard ratio) of EFS (P5.003), with a coefficient of determination of 0.68 (95% CI, 0.41-0.95). There was a weaker association between PCR and OS (P5.18), with a coefficient of determination of 0.24 (95% CI, 0.01-0.77). Consistent results were found in the exploratory analysis and sensitivity analyses. Conclusions: This is the first study that has shown a trial-level association between PCR and survival outcomes in TNBC. By incorporating the most upto- date RCTs, this study showed a significant trial-level association between PCR and EFS. A positive association between PCR and OS was also recorded.