In a study reported in the Journal of Clinical Oncology, Squifflet et al found that pathologic complete response (pCR) was a weak surrogate for event-free and overall survival in neoadjuvant trials of anti-HER2 therapy in patients with HER2-positive early breast cancer.
In the study, individual-patient data were obtained from randomized trials of neoadjuvant therapy including anti-HER2 therapy that enrolled at least 100 patients; had data for pCR, event-free survival, and overall survival; and had a median follow-up of at least 3 years. The patient-level association between pCR (defined as ypT0/Tis ypN0) and both outcomes were quantified using odds ratios, with odds ratios of > 1.0 indicating a benefit from achieving pCR. Trial-level associations were assessed using R2, with values of > 0.75 indicating a strong association.
A total of 11 trials were included in the analysis, comprised of 3,980 patients with a median follow-up of 62 months.
For patients with vs without pCR, hazard ratios were 0.42 (95% confidence interval [CI] = 0.36–0.49, P < .001) for event-free survival and 0.34 (95% CI = 0.27–0.43, P < .001) for overall survival. Strong patient-level associations of pCR with event-free survival (odds ratio [OR] = 2.64, 95% CI = 2.20–3.07) and overall survival (OR = 3.15, 95% CI = 2.38–3.91) were observed.
Weak trial-level associations of pCR with event-free survival (unadjusted R2 = 0.23, 95% CI = 0.0–0.66) and overall survival (unadjusted R2 = 0.02, 95% CI = 0.0–0.17) were observed.
Qualitatively similar results were obtained in analyses grouping trials according to different clinical questions, including only patients with hormone receptor–negative disease, and using a more stringent definition of pCR (ypT0 ypN0).
The investigators concluded, “Although pCR may be useful for patient management, it cannot be considered as a surrogate for event-free survival or overall survival in neoadjuvant trials of HER2-positive, operable breast cancer.”
Everardo D. Saad, MD, of the International Drug Development Institute, Louvain-la-Neuve, Belgium, is the corresponding author for the Journal of Clinical Oncology article.
Disclosure: The study was supported by the German Breast Group. For full disclosures of the study authors, visit ascopubs.org.The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.