SABCS 2016. P5-16-17. Population based long-term outcomes of pathologic complete response after neoadjuvant chemotherapy in stage I-III breast cancer: The British Columbia experience
Sun J, Lovedeep G, Diocee R, Speers C, Lohrisch C and Chia S.
Results: 267 pts who met inclusion criteria were identified, of whom 5% had stage I, 33% Stage II and 59% Stage III breast cancer. Median follow up was 7.4 years. Overall 74 pts (28%) demonstrated a pCR and 193 pts did not. pCR pts had better 5-yr overall survival (OS) vs. non-pCR pts: 88% vs. 73% (HR 0.43, 95% CI 0.23-0.82, p=0.01). 5-yr disease free survival (DFS) was 84% in pCR pts vs. 70% in non-pCR pts (HR 0.45, 95% CI 0.24-0.83, p=0.01). Similarly, 5-yr breast cancer specific survival (BCSS) and distant disease free survival (DDFS) were significantly better in favor of the pCR cohort: HR 0.39 (95% CI 0.18-0.82, p=0.01) and HR 0.45 (95% CI 0.24-0.83, p=0.02) respectively. pCR pts were more likely to be HER2-positive and/or ER negative.
Conclusions: Our population based results showed that early stage breast cancer pts who achieved pCR after neoadjuvant chemotherapy had better outcomes on all survival parameters compared to pts who did not achieve a pCR. This finding is consistent with results from neoadjuvant clinical trials and the FDA meta-analysis. These ‘real world’ results demonstrate that pCR can be used as a surrogate endpoint for survival outcomes even among non-trial pts.
CARE™ Faculty Perspective: Though controversy continues as to the applicability of pCR as a surrogate for long-term clinical outcomes, much of that pertains to trial participation relative to ‘real world’ experience. This population based experience from British Columbia supports that pCR is a surrogate, and most impressively the hazard ratio for DFS was almost identical to the FDA meta-analysis for EFS (HR 0.48). Most regulatory authorities (FDA and EMEA) have embraced this association, and it is now time for the Canadian counterpart and review guidance panels to also accept the correlation so that new therapeutic agents with demonstrated benefit in both advanced stage and pre-operative stage trial settings can reach all suitable and eligible patients sooner rather than later.