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Patients with breast cancer who respond to neoadjuvant treatment may not need adjuvant chemotherapy
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SAN ANTONIO — Patients with breast cancer who achieved pathologic complete response to neoadjuvant chemotherapy attained similar survival outcomes regardless of whether they underwent adjuvant chemotherapy, according to results of a comprehensive patient-level meta-analysis presented at San Antonio Breast Cancer Symposium.
The consistency of outcomes with regard to recurrence and survival likely reflects tumor biology and indicates adjuvant chemotherapy could potentially be omitted in certain circumstances, Laura M. Spring, MD, medical oncologist at Massachusetts General Hospital Cancer Center and instructor in medicine at Harvard Medical School, and colleagues concluded.
“Our research overall supports escalation and de-escalation strategies, but it would be important that the specific strategies be explored in a clinical trial,” Spring told HemOnc Today. “There are standard therapies that are recommended but, with good evidence, I think many clinicians would be open to a de-escalation strategy.”
Breast cancer trials traditionally have focused on providing additional systemic therapies to reduce risk for recurrence. However, those additional therapies can lead to additional toxicity with no guarantee of accompanying benefit.
Prior studies have demonstrated the prognostic potential of pathologic complete response (pCR) following neoadjuvant chemotherapy, but the effect of subsequent adjuvant therapy in modulating the association between pCR and long-term outcomes has not been established, according to study background.
Spring and colleagues conducted a meta-analysis to examine the association between pCR and clinical outcomes — specifically EFS and OS — by breast cancer subtype. They also assessed the effect of adjuvant chemotherapy on the association between pCR and clinical outcomes.
They defined pCR as no sign of invasive cancer in the breast tissue or lymph nodes.
Researchers used PubMed to identify studies that included patients with localized breast cancer who underwent neoadjuvant chemotherapy.
The analysis included 52 studies (n = 27,895) conducted between 1999 and 2016. All studies included at least 25 patients who underwent neoadjuvant chemotherapy and had reported pCR results, as well as recurrence and survival data based on pathologic outcomes.
Studies that only reported local recurrence, as well as studies that included neoadjuvant radiation or neoadjuvant endocrine therapy, were excluded.
Investigators used a random effects model to account for treatment variations between studies. They also performed several sensitivity analyses to confirm results.
Overall, patients who achieved pCR were significantly less likely than those who had residual disease to experience disease recurrence (HR = 0.31; 95% prediction interval, 0.24-0.39).
Five-year EFS rates of 88% for those who achieved pCR after neoadjuvant chemotherapy and 67% for those who had residual disease. This improvement in 5-year EFS after pCR persisted when researchers analyzed patients by subtype, including triple-negative breast cancer (90% vs. 57%), HER2-positive (86% vs. 63%) and hormone receptor-positive/HER2-negative disease (97% vs. 88%).
Achievement of pCR also appeared associated with a statistically significant improvement in OS (HR = 0.22; 95% prediction interval, 0.15-0.3; 5-year OS rate, 94% vs. 75%). This OS benefit also persisted when researchers analyzed outcomes based on disease subtype.
Spring and colleagues then evaluated EFS outcomes among patients who achieved pCR after neoadjuvant chemotherapy based on whether they received adjuvant chemotherapy.
Results showed pCR was associated with significantly improved EFS regardless of whether patients received adjuvant chemotherapy (HR = 0.36; 95% prediction interval, 0.19-0.67) or did not (HR = 0.36; 95% prediction interval, 0.27-0.54), with no significant difference between groups.
Five-year EFS rates were 86% among those who received adjuvant chemotherapy and 88% among those who did not.
The researchers also created a statistical model to demonstrate the relationship between the magnitude of pCR change and the corresponding change in EFS and OS. The model may provide guidance for clinical trials that assess neoadjuvant therapies for patients with localized breast cancer, researchers said.
The strengths of the study included its large sample size, inclusion of both retrospective and trial studies, inclusion of patients from around the world, and the attainment of highly significant results despite the fact that studies of several neoadjuvant regimens were included in the analysis, Spring said.
She also acknowledged several limitations, including variability in the study populations, regimens received, study-specific outcome definitions and definitions of hormone receptor positivity.
Additional research is necessary to assess the clinical utility of escalation or de-escalation strategies in the adjuvant setting based on neoadjuvant response, Spring said.
“There are planned studies looking at HER2-positive breast cancer in which patients will receive anti-HER2 therapies combined with one cytotoxic chemotherapy agent in the preoperative setting, and if they achieve a pCR, they will not receive additional cytotoxic chemotherapy after [surgery],” Spring told HemOnc Today. “There also are trial designs in which you could give some cytotoxic chemotherapy and then, instead of waiting until surgery to assess response, you could perform MRI or even a biopsy to determine if a patient achieve pCR or not. If not, you could opt to give them additional cytotoxic chemotherapy before surgery. If they did, you could spare them the additional regimen.” – by Mark Leiser
Reference:
Spring LM, et al. Abstract GS2-03. Presented at: San Antonio Breast Cancer Symposium; Dec. 4-8, 2018; San Antonio.
Disclosure:
Grants from NCI and Susan G. Komen supported this study. Spring reports consultant or advisory roles with Novartis, as well as institutional research funding from Tesaro. Please see the abstract for all other authors’ relevant financial disclosures.