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Zusammenfassung: <jats:p> e13033 </jats:p><jats:p> Background: Panel sequencing (PS) has become a standard-of-care in cancer diagnostics. More comprehensive analyses such as whole-exome (WES) or RNA sequencing (RNAseq) allow for the detection of rare and unknown genetic aberrations that are not covered by predefined assays. The clinical impact of targeted versus comprehensive genomic assays were analyzed in patients presented at the Charité Molecular Tumor Board (MTB). Methods: Patients (pts) with advanced and/or metastatic cancer for whom no standard therapy was available were discussed in the MTB to allocate diagnostic profiling and guide biomarker-based treatment (BBT). Pts had to be &lt; 50 years of age or diagnosed with a rare tumor entity to undergo WES/RNAseq, performed on fresh tissue. If ineligible, standard PS was performed on archival tissue. BBT recommendations, ranked by pre-specified evidence levels, were made by the MTB and pts were followed up. Results: 228 patients (median age 49 years, 108 female and 120 male) were discussed in the MTB between January 2016 and February 2019. We assigned 73 and 155 pts to PS and WES/RNAseq and results were obtained for 78.1% (n = 57/73) and 54.8% (n = 85/155) pts, respectively. Sequencing failed for 11 (PS; 15.1%) and 62 (WES/RNAseq; 40%) pts, most commonly due to insufficient tissue (n = 29). Sequencing was ongoing in 5 (PS) and 8 (WES/RNAseq) pts at the time of analysis. A median of 2 BBTs were recommended for 75.4% (43/57) of PS (range r: 1-3) and 90.6% (77/85) of WES/RNAseq pts (r: 1-6) each. 22% (n = 17/77) of WES/RNAseq pts had ≥4 BBTs made by the MTB. Treatment was initiated in 30.2% (n = 13/43) of PS and 40.2% (n = 31/77) of WES/RNAseq pts. Clinical benefit rates (CBRs) were 23.1% (2 PR, 1 SD) for PS and 45.2% (2 CR, 3 PR, 9 SD) for WES/RNAseq pts. Overall survival data was immature at the time of analysis. Conclusions: Utilizing WES/RNAseq is a feasible approach to perform tumor profiling in a heterogeneous cohort. We here show a higher rate of pts receiving confident evidence-based treatment recommendations in the WES/RNAseq group and a higher rate of treatment initiation. The CBR nearly doubled in the WES/RNAseq cohort when compared to standard PS pts, thus emphasizing the need for larger comparative analyses to guide diagnostic decision-making. </jats:p>
Umfang: e13033-e13033
ISSN: 0732-183X
1527-7755
DOI: 10.1200/jco.2019.37.15_suppl.e13033