Most anticancer drugs are approved by making marginal improvements in terms of tumor response or survival in non-selected populations, and are highly heterogeneous at the molecular level. Studying patients who present an exceptional and unexpected response (ER) to these drugs could enable the rapid identification of novel treatment response biomarkers, accelerate drug development and, more broadly, lead to a better understanding of the biology of cancer cells. Several studies are currently recruiting to build cohorts of patients, in order to subsequently analyze their tumors and reveal in detail the molecular anomalies associated with exceptional response.
This is an exploratory, multicenter, multicohort, prospective trial conducted in 264 adult patients, with advanced breast, lung, colorectal, ovarian, kidney cancers and melanoma, having presented an ER to an approved antineoplastic targeted therapy. ER is defined using the definition chosen by the NCI which combines the three criteria: -complete or partial response -lasting > 6 months -and not expected in > 10% of the patients in this drug – organ situation. The primary objective is to assess whether ER can be associated with a low level of genomic instability in the tumor. Low genomic instability is defined by the presence of less than the 5th quantile of genomic alterations (mutations, amplifications, deletions) to be expected in the given tumor type as per TCGA database. For each tumor type, the null hypothesis H0: π = 0.05 will be tested, against the one-sided alternative hypothesis π > 0.05. For each of the 6 cohorts, a sample size of 44 patients is necessary to achieve 80% power at π = 15 with a one-sided level 5% test. Patients presenting an ER will be identified retrospectively, in a nationwide manner, then monthly reviewed and validated for inclusion by a panel of pathology experts. As of May 2018, 56 patients have been included. The identification of molecular traits associated with ER might serve the development of predictive classifiers for precision medicine. This study also represents a unique opportunity to better understand cancer biology.
Clinical trial identification
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All authors have declared no conflicts of interest.