Precision Medicine is based on the development of rationally designed target-based (RDTB) new drugs that inhibit genomically defined alterations in their tumors. The aim of this study is to evaluate the difficulties and efficiency of the implementation of tumor molecular profiling and prescreening as the bases for recruitment of cancer patients in a program of early phase clinical trials
This is a retrospective evaluation of the molecular profile of patients, preliminary candidates to phase 1 clinical trials at the Madrid sites of the START Early Clinical Drug Development, between 2011 and 2017. Our primary focus is enrollment efficiency on studies of RDTB drugs with molecular prescreening based on Next Generation Sequencing (NGS) (FoundationOne Medicine assay) and immunohistochemistry (IHC) (DS6 and MET expression)
We analyzed 1196 patients; 228 did not have archived tissue to perform the test and new biopsy was not feasible. 345 (35.6%) of 968 with a valid sample had molecular alterations; of these, 233 (24.07%) were detected by NGS, and 174 were potentially actionable genes, such as FGFR family (27%), PI3K (23.5%), ERRB2 (9.7%) and KRAS (8.6%). 120 patients (12.39%) had a positive result by IHC, 1 patient (0.83%) for MET, and 119 (99.16%) with DS6 expression. All together, 294 patients had a positive test, 90 (9.3%) patients, 45 of the NGS group and 45 of the IHC group, were actually enrolled on a matched clinical trial for the alteration documented. 204 were not enrolled: 74 (25.1%) enrolled on a more rapidly available non-targeted drug trial, 61(20.7%) did not satisfy selection criteria, 56 (19%) were treated with standard therapies, 5 (3%) had a rapid clinical deterioration, and 8 (2.7%) never came back to our units.3.67% of the 1196 patients had a clinical benefit with this approach
An almost negligible proportion of prescreened patients actually obtained clinical benefit from this approach. We have identified as main reasons: prolonged time derived from central screening testing, additional selection criteria of clinical trials, and lack of slots; some of these are correctable. The proportion of patients identified by NGS and IHC were similar in our series.
Clinical trial identification
Legal entity responsible for the study
Has not received any funding.
All authors have declared no conflicts of interest.