Molecularly-matched therapy (MMT) is associated with increased response rates and in some cases with improved survival. Next generation sequencing (NGS) - based multigene panels offer a wide range of analyzed markers. There is a need to optimize comprehensive profiling and find the most relevant molecular targets according to tumor type.
Retrospective analysis of NGS reports and clinical data of patients with advanced gastrointestinal tumors was performed. The frequency of detected molecular alterations in each cancer type, the frequency of MMT recommendation were assessed. Efficacy was estimated using progression-free survival (PFS) ratio (PFS2/PFS1).
Between 2019 and 2023, tumor samples from 107 patients with gastrointestinal tumors were analyzed using NGS-based panels (colorectal cancer (CRC) - 64 patients (59%), pancreatic cancer (PCa) - 21 (20%), cholangiocellular cancer (CCC) - 12 (11%), gastric cancer (GC) - 11 (10%). Median age was 58 years, median number of lines before analysis - 2. MMT after NGS was administered to 17 patients (16%). Of these patients 6 samples were assesed as ESCAT I tier (35%), 2 (12%) - ESCAT IIB, 2 (12%) - ESCAT IIIA, 7 (51%) - ESCAT IIIB. PFS2/1 ratio≥1,3 was reached in 10 patients (59%). In the cohort of patients who have not been prescribed MMT, the PFS ratio was available for 42 patients, among whom 11 patients (26%) achieved PFS1/2 ≥1,3 (p=0,005). MMT was the only favorable predictor of PFS2/1 ≥1.3 (HR 0.13; 95% CI 0.03 - 0.50, p=0.003) in univariate analysis. Median overall survival in the MMT and non-MMT groups was 6 and 5 months, respectively (HR=2.07; 95% CI 1.01 - 4.26). Table: 164P
|HR (95% CI)||p value|
|Age, years ≥60 <60||1,00 0,80 (0,21 -2,91)||0,72|
|Number of lines before analysis, ≤1 ≥2||1,00 0,67 (0,16 - 2,86)||0,59|
|Sex, m f||1,60 (0,45 - 5,70) 1,00||0,47|
|Molecular tumor board Yes No||1,00 0,61 (0,13 - 2,85)||0,53|
|RAS RASwt RASmut||1,00 (0,28 - 3,61) 1,00||1,00|
|MMT Yes No||1,00 0,13 (0,03 - 0,50)||0,003|
MMT may potentially have advantages over non-MMT in advanced gastrointestinal cancers when standard therapy options are limited. In order to optimize testing in routine practice, it is necessary to create more limited panels for profiling according to each tumor type.
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All authors have declared no conflicts of interest.