Pathologic complete response (pCR) following neoadjuvant chemotherapy appeared to be associated with improved survival outcomes among patients with breast cancer, according to meta-analyses data presented at the 2018 San Antonio Breast Cancer Symposium.
Patients who experienced pCR were 69% less likely to have disease recurrence compared with their counterparts with residual disease (HR, 0.31; 95% probability intervals [PI], 0.24-0.39). Moreover, event-free (EFS) and overall survival (OS) outcomes appeared comparable regardless of whether or not patients received adjuvant chemotherapy.
“Traditionally, breast cancer trials have focused on adding additional systemic therapies to reduce recurrence risk. However, adding therapies can result in additional toxicity and overtreatment for many patients,” Laura Spring, MD, medical oncologist at Massachusetts General Hospital Cancer Center and instructor in medicine at Harvard Medical School, said during a press conference at the meeting.
“The neoadjuvant chemotherapy model offers several additional advantages over adjuvant chemotherapy, including rapid assessment of treatment responses utilizing surrogate biomarkers such as pathological complete response,” she added.
The association between pCR and EFS was strongest among patients with triple-negative or HER2-positive breast cancer, who were 82% and 68%, respectively, less likely to have disease recurrence following pCRdefined as the lack of all signs of invasive cancer in the breast tissue and lymph nodes removed during surgery after treatment with chemotherapy. Patients with hormone receptor (HR)–positive/HER2-negative breast cancer who had pCR also demonstrated a trend toward lower risk for recurrence; however, the data were not statistically significant.
In addition, patients with pCR showed a 78% lower risk for mortality compared with those who did not have pCR (HR, 0.22; 95% PI, 0.15-0.30), a trend that was consistent among the triple-negative, HER2-positive, and HR-positive/HER2-negative subgroups.
Five-year EFS (88% vs 67%) and OS (94% vs 75%) were also significantly superior in patients with pCR compared with those with residual disease. Comparably, the triple-negative (90% vs 57%), HER2-positive (86% vs 63%), and HR-positive/HER2-negative (97% vs 88%) subgroups demonstrated improved EFS, with similar results seen in OS.
The 5-year EFS in patients with pCR followed by adjuvant chemotherapy was 86% compared with 88% of those who had pCR without additional adjuvant chemotherapy. The association between pCR and reduced recurrence was comparable and there was no significant difference in hazard ratios between both groups (66% vs 64%; paired T-test difference in log-HR, 0.02; 95% PI, 0.75-0.73; P
“The similar outcomes with or without adjuvant chemotherapy in patients who attain pCR after neoadjuvant chemotherapy likely reflects tumor biology and suggests adjuvant chemotherapy could potentially be omitted in certain circumstances,” Spring said.
To evaluate the potential association between pCR after neoadjuvant therapy and subsequent breast cancer recurrence, as well as to evaluate the impact of adjuvant chemotherapy on the relationship between pCR and patient outcomes, the researchers conducted a comprehensive patient-level meta-analysis of 52 studies, found from 1999 to 2016, that included 27,895 individuals who underwent a variety of treatments.
The meta-analysis included published studies of localized breast cancer with 25 patients or more featuring neoadjuvant chemotherapy that reported pCR results as well as recurrence and/or survival based on pathologic outcome. Studies reporting on local recurrence only or those featuring neoadjuvant endocrine therapy or neoadjuvant radiation were excluded from analysis.
The researchers noted that, assuming pCR is a valid surrogate endpoint, the magnitude of pCR change is predictive of treatment effects on EFS within a certain amount of uncertainty, based on the model, which in turn, could be a helpful design for neoadjuvant studies, Spring said.
“Further research is needed to evaluate the clinical utility of escalation/de-escalation strategies in the adjuvant setting based on neoadjuvant response,” she added. “…This (study) supports strategies where maybe you use less cytotoxic chemotherapy and try to identify that group that will have a pCR with a de-escalation strategy, and then you spare them hopefully from additional cytotoxic chemotherapy.”
Spring LM, Fell G, Arfe A, et al. Pathological complete response (pCR) after neoadjuvant chemotherapy and impact on breast cancer recurrence and survival, stratified by breast cancer subtypes and adjuvant chemotherapy usage: Patient-level meta-analyses of over 27,000 patients. In: Proceedings from the 2018 San Antonio Breast Cancer Symposium (SABCS); Dec. 4–8, 2018; San Antonio, Texas.
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