Comprehensive genomic profiling in routine clinical practice leads to a low rate of benefit from genotype-directed therapy

Abstract

BackgroundDescribe a single-center real-world experience with comprehensive genomic profiling (CGP) to identify genotype directed therapy (GDT) options for patients with malignancies refractory to standard treatment options.MethodsPatients who had CGP by a CLIA-certified laboratory between November 2012 and December 2015 were included. The medical records were analyzed retrospectively after Institutional Review Board (IRB) approval. The treating oncologist made the decision to obtain the assay to provide potential therapeutic options. The objectives of this study were to determine the proportion of patients who benefited from GDT, and to identify barriers to receiving GDT.ResultsA total of 125 pediatric and adult patients with a histologically confirmed diagnosis of malignancy were included. Among these, 106 samples were from adult patients, and 19 samples were from pediatric patients. The median age was 54 years for adults. The majority had stage IV malignancy (53%) and were pretreated with 2–3 lines of therapy (45%). The median age was 8 years for pediatric patients. The majority had brain tumors (47%) and had received none or 1 line of therapy (58%) when the profiling was requested. A total of 111 (92%) patients had genomic alterations and were candidates for GDT either via on/off-label use or a clinical trial (phase 1 through 3). Fifteen patients (12%) received GDT based on these results including two patients who were referred for genomically matched phase 1 clinical trials. Three patients (2%) derived benefit from their GDT that ranged from 2 to 6 months of stable disease.ConclusionsCGP revealed potential treatment options in the majority of patients profiled. However, multiple barriers to therapy were identified, and only a small minority of the patients derived benefit from GDT.

Feasibility of next-generation sequencing in clinical practice: results of a pilot study in the Department of Precision Medicine at the University of Campania ‘Luigi Vanvitelli’

“…The idea of being able to treat all patients, each with a drug suitable for the specific alterations of his tumour, is certainly attractive for oncologists and especially for patients. In our work, we evaluated the feasibility of First, we evaluated the overall success rate, which was lower (68.85%) than in other similar works, [9][10][11][12] due to several reasons. Foremost, in a significant percentage of cases, tissue qualification was not performed locally before the shipment: a local preassessment could potentially reduce the failure rate.…”

“…They found similar genes and pathway involved to our work with higher percentage of patients treated with genotype directed therapy (12%-35%). [9][10][11][12] Considering the time of follow-up of our study (in most of patients F1CDx was performed in the last 6 months of the study), and the fact that many patients did not progress to their ongoing therapies, probably we will reach this percentage during next years. Indeed, a good number of prospective [17][18][19][20][21][22][23] and retrospective [24][25][26][27] trials evaluated CGP using different techniques (NGS, WES, WGS) but in the context of large academic centres.…”

Impact and Diagnostic Gaps of Comprehensive Genomic Profiling in Real-World Clinical Practice

“…Several studies, mostly from large academic centers, have reported successful implementation of CGP and have shown that most patients will have at least one potentially actionable genomic alteration on CGP. In a retrospective study of 125 patients who underwent CGP, clinically relevant genetic alterations were found in 111 (92%) patients [15]. Only 15 (12%) patients received molecularly targeted therapy, with three who derived clinical benefit.…”

Oncologist uptake of comprehensive genomic profile guided targeted therapy

“…Payers have potentially overlooked CGP as a sophisticated testing approach that informs complex clinical decision-making and enables a patient’s next best care option, be it drug therapy or no further treatment. A few studies have assessed the benefits of CGP for treatment decisions, but results often have limited generalizability with patients tested in the context of prospective studies intended to enroll patients in targeted therapy trials [13–18], limited histologies [19], using retrospective physician questionnaires with modest response rates at the patient level [20, 21], or most commonly, in the context of large academic center molecular tumor boards [22–26].…”