PATHOLOGICAL COMPLETE RESPONSE TRIAL

The Pharma has latched on to this and made this THE goal in breast and other cancers to tout their products. Īs an Academic turned Community Oncologist,I can tell you that there is not one oncologist who is NOT totally convinced about the pCR and EFS as the Holy Grail of NeoAdj therapy. So, for 9 years since the NeoSphere and 8 years since the FDA sponsored Cortana study, the misconceptions or at least scientifically weak concepts about surrogacy of pCR and EFS haveīeen allowed to unjustifiably cement in the minds of many.

Thus, there is currently insufficient evidence to support EFS for use as a surrogate endpoint for traditional approval, although it may be considered for accelerated approval.” “Treatment effects in EFS are moderately correlated with treatment effects in OS in early breast cancer in the neoadjuvant setting, but the association was not significant. There is an analysis published in The Lancet looking at EFS as a predictor of OS in the same setting and concludes thus: His concern was the same as expressed in this article. Eric Winer expressed dismay at the FDA’s decision to confer surrogacy to pCR for OS in NeoSphere trial. In an article in JCO titled “ Perils of the pCR” Dr.

PATHOLOGICAL COMPLETE RESPONSE TRIAL

The surrogacy value at trial level of potentially more robust surrogate end points needs to be urgently tested. Evidence currently available does not support pCR used alone as a reliable surrogate end point in regulatory neoadjuvant RCTs for BC. Such proposed surrogate end points could overcome limits of pCR and provide a reasonable trade-off between the 2 conflicting needs to have access to effective therapies rapidly, and to reliably assess patients’ clinical benefit.Ĭonclusions and Relevance Using surrogate end points to grant drug approvals is justified only when they can provide accurate prediction of a drug’s effect on the long-term patient outcomes. We also describe alternative surrogate end points, including combined end points that jointly analyzed pathological response and event-free survival data, or the assessment of circulating tumor DNA (ctDNA). Observations We critically discuss the potential reasons of such discrepancy between pCR surrogacy value at the patient and trial level, as well as the relevant implications for both clinical research and drug regulatory policy.

However, a meaningful association between pCR and patients’ survival has been proven only at the patient level (ie, significantly better survival of patients who achieved pCR compared with those who did not), but not at trial level (ie, poor association between degree of improvement in pCR rate and survival reported across trials). Importance The pathologic complete response (pCR) is supported by regulatory agencies as a surrogate end point for long-term patients’ clinical outcomes in the accelerated approval process of new drugs tested in neoadjuvant randomized clinical trials (RCTs) for early breast cancer (BC).

Pathological complete response