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The US regulator's pooled analysis of 11,955 patients in 12 trials that found complete disappearance of the tumour before surgery predicts survival most strongly in triple-negative disease, but that a trial raising the complete response rate does not reliably improve survival.
Cortazar, Zhang, Untch, Mehta and colleagues pooled 12 international neoadjuvant trials with at least 200 patients, response and survival data and three years of follow-up (11,955 patients), comparing three definitions of pathological complete response and testing trial-level surrogacy. Eradication from breast and nodes (ypT0 ypN0, or ypT0/is ypN0) associated better with event-free survival (hazard ratios 0.44 and 0.48) and overall survival (0.36 for both) than eradication from the breast alone (0.60 and 0.51). The association was strongest in triple-negative breast cancer (event-free survival hazard ratio 0.24, 95 percent confidence interval 0.18 to 0.33; overall survival 0.16, 0.11 to 0.25) and in HER2-positive, hormone receptor-negative disease treated with trastuzumab. At trial level there was little association between increases in pathological complete response and event-free (R squared 0.03) or overall survival (0.24), so the analysis could not validate pathological complete response as a surrogate endpoint.
The basis of the US accelerated approval pathway on pathological complete response that KEYNOTE-522 and neoadjuvant trials since have used, together with the warning that a higher response rate in a trial is a promise, not a proof, of longer life.
Shares Hazard ratio (HR), Event-free / disease-free survival (EFS, DFS, iDFS, RFS), Triple-negative breast cancer roadmap: from a remainder defined by three negative tests to immunotherapy, antibody-drug conjugates and the residual disease problem, HER2-positive breast cancer and the tag tnbc-evidence.
Shares Response to neoadjuvant therapy and long-term survival in patients with triple-negative breast cancer, Hazard ratio (HR), Triple-negative breast cancer roadmap: from a remainder defined by three negative tests to immunotherapy, antibody-drug conjugates and the residual disease problem, Triple-negative breast cancer (TNBC) and the tag tnbc-evidence.
Shares Give exceptional responders less: pembrolizumab omission after complete response, anthracycline-free regimens and chemotherapy omission in lymphocyte-rich stage I disease, Hazard ratio (HR), Triple-negative breast cancer roadmap: from a remainder defined by three negative tests to immunotherapy, antibody-drug conjugates and the residual disease problem, Triple-negative breast cancer (TNBC) and the tag tnbc-evidence.
Shares Give exceptional responders less: pembrolizumab omission after complete response, anthracycline-free regimens and chemotherapy omission in lymphocyte-rich stage I disease, HER2-positive breast cancer, Triple-negative breast cancer (TNBC) and the tag tnbc-evidence.
Shares Triple-negative breast cancer roadmap: from a remainder defined by three negative tests to immunotherapy, antibody-drug conjugates and the residual disease problem, HER2-positive breast cancer, Triple-negative breast cancer (TNBC) and the tag tnbc-evidence.
Shares Hazard ratio (HR), Triple-negative breast cancer roadmap: from a remainder defined by three negative tests to immunotherapy, antibody-drug conjugates and the residual disease problem, Triple-negative breast cancer (TNBC) and the tag tnbc-evidence.
Shares Event-free / disease-free survival (EFS, DFS, iDFS, RFS), Pathologic complete response (pCR), Triple-negative breast cancer roadmap: from a remainder defined by three negative tests to immunotherapy, antibody-drug conjugates and the residual disease problem, Triple-negative breast cancer (TNBC) and the tag tnbc-evidence.
Shares Pathologic complete response (pCR), Triple-negative breast cancer roadmap: from a remainder defined by three negative tests to immunotherapy, antibody-drug conjugates and the residual disease problem, HER2-positive breast cancer, Triple-negative breast cancer (TNBC) and the tag tnbc-evidence.