Clinical management of molecular alterations identified by high throughput sequencing in patients with advanced solid tumors in treatment failure: Real-world data from a French hospital

Abstract

BackgroundIn the context of personalized medicine, screening patients to identify targetable molecular alterations is essential for therapeutic decisions such as inclusion in clinical trials, early access to therapies, or compassionate treatment. The objective of this study was to determine the real-world impact of routine incorporation of FoundationOne analysis in cancers with a poor prognosis and limited treatment options, or in those progressing after at least one course of standard therapy.MethodsA FoundationOneCDx panel for solid tumor or liquid biopsy samples was offered to 204 eligible patients.ResultsSamples from 150 patients were processed for genomic testing, with a data acquisition success rate of 93%. The analysis identified 2419 gene alterations, with a median of 11 alterations per tumor (range, 0–86). The most common or likely pathogenic variants were on TP53, TERT, PI3KCA, CDKN2A/B, KRAS, CCDN1, FGF19, FGF3, and SMAD4. The median tumor mutation burden was three mutations/Mb (range, 0–117) in 143 patients with available data. Of 150 patients with known or likely pathogenic actionable alterations, 13 (8.6%) received matched targeted therapy. Sixty-nine patients underwent Molecular Tumor Board, which resulted in recommendations in 60 cases. Treatment with genotype-directed therapy had no impact on overall survival (13 months vs. 14 months; p = 0.95; hazard ratio = 1.04 (95% confidence interval, 0.48–2.26)].ConclusionsThis study highlights that an organized center with a Multidisciplinary Molecular Tumor Board and an NGS screening system can obtain satisfactory results comparable with those of large centers for including patients in clinical trials.

A Real-World Study Reporting the Use of Foundation Medicine® Testing in Portugal

“…The median age of the patients included in our study was 60.5 (range 27-82) years, which is similar to the median age of the population reported in different studies that analysed solid tumour samples with the Foundation Medicine ® platform [17][18][19][20]. A total of 72 samples were processed for the identification of genomic alterations, and data were obtained for 67 samples, corresponding to a success rate of 93.1%.…”

“…Despite the presented data and the potential benefits that patients can gain following the development of precision oncology, most of the genomic alterations identified in this study have no direct match with currently approved drugs, as reported in other large series using the same test [17][18][19]. One such example in this study is the cancers of unknown primary, which presented KRAS alterations.…”

THERANOVA-LIM: Optimizing the city hospital link to support patients on oral anticancer drugs

“…In addition, a Hawthorne effect may be in play; patients who are aware that they are being surveyed may (consciously or unconsciously) overestimate their compliance rates [41]. Recruitment bias may be in play; many patients had brain tumors (our center has expertise in this eld) [18,42]. However, unlike other studies, we did not select particular types of tumors and the QR code was available to all cancer patients.…”