Pathologic Complete Response as Surrogate for Event-Free and Overall Survival in Neoadjuvant Trials in HER2-Positive Early Breast Cancer

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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.

Study Details

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.

Key Findings

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

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