Prevalence of CLDN18.2, HER2 and PD-L1 in gastric cancer samples

Abstract

recommended in front line in this setting in France. Replicate plasma samples were analysed using OncoBEAM and NGS. The thresholds for calling EGFR plasma mutations were 0.5% and 0.02% for NGS and OncoBEAM, respectively and were validated using cfDNA reference standards (Horizon Discovery). Results: OncoBEAM detected the p.T790M mutation in 36/196 patients (18.3%), whereas NGS detected T790M in 20/196 patients (10.2%). The agreement of NGS vs OncoBEAM for T790M detection was 55.6%. The p.T790M-positive samples detected by OncoBEAM but missed by NGS were all found to have low mutant allelic fractions (under 0.35%). With regard to sensitizing EGFR mutations, 28/36 OncoBEAM T790Mþ patients had accompanying EGFR mutations, whereas all 20/20 NGS T790Mþ samples showed presence of sensitizing mutations. In contrast to OncoBEAM, NGS testing revealed other somatic alterations including ERBB2 amplification , and mutations in TP53. Conclusions: In conclusion, these findings highlight the value of OncoBEAM TM-EGFR and NGS for detecting T790M at early progression. While less sensitive, NGS provided broader genomic coverage which may reveal diverse mechanisms of resistance. In contrast , OncoBEAM delivers superior sensitivity for focused detection of known resistance alterations such as EGFR T790M. Thus, OncoBEAM may provide the sensitivity required to monitor the kinetics of circulating tumor DNA and correlations with therapeutic response. Background: The activity of immune checkpoint inhibitors (ICIs) varies substantially at the extremes of age. We interrogated our tissue database (n ¼ 1,467) to determine if expression of checkpoint molecules or variations in tumor mutational burden (TMB) could explain this phenomenon. Methods: Whole transcriptomic sequencing (RNA-Seq; 200x10 6 reads/tumor) was performed across 1,467 unselected clinical cases (NantHealth; Culver City, CA), with breast, colon, lung and sarcoma reflecting the most common tumor types assessed. To reflect the extremes of age, patients age < 25 and 80 were compared to the remainder of the cohort. PD-L1 expression was compared across these age-based subsets, along with CTLA4, TIGIT, FOXP3, LAG3, OX40, TIM3 and IDO expression. Putative markers of ICI resistance (e.g, VEGF-A/B/C) were also explored. Tumor mutational burden (TMB; defined as exonic nonsynonymous mutations/megabase [muts/Mb]) was characterized in each subset. Results: Median age of the cohort was 59 (range, 2-97). Of 1,467 patients, 84 and 65 were age < 25 and 80, respectively. In patients < 25, significantly lower PD-L1, CTLA4, FOXP3, OX40, LAG3 and TIGIT levels were observed (P < 0.001 for each). No significant differences in IDO, LAG3 or TIM3 were observed in this younger cohort. Older patients had no significant differences in checkpoint molecule expression; curiously , a nonsignificant trend towards increased expression of PD-L1, FOXP3 and LAG3 was observed in the small subset of patients age 85. No differences in TMB were observed by age. Expression and TMB in each decile of age will be reported. Conclusions: In pediatric and adolescent and young adult (AYA) patients, lower expression of multiple immune checkpoint molecules may have implications for immune combinatorial strategies. An opposing trend was seen in octagenarians and nonagenarians in our cohort. A detailed further breakdown by histologic subtype will be presented. Background: Crizotinib have greatly improved the prognosis of ROS1þ lung adeno-carcinoma. However, approximately 5% to 10% of patients with ROS1þ non-small-cell lung cancer (NSCLC) have primary resistance to crizotinib treatment. The underlying mechanism is unknown. Methods: We screened 2617 patients with NSCLC for ROS1 fusion. Among them, 23 patients received crizotinib treatment, and a total of 20 patients with stage IIIb-IV ROS1þ NSCLC were undergoing tumor biopsies or blood withdrawing by the time of primary or acquiring resistance to crizotinib, in including 4 formalin-fixed paraffin-embedded (FFPE) samples, 13 serum samples and 3 serous effusions. We used targeted NGS to detect genes status of patients. Results: Among 23 patients treated with crizotinib, 73.9% (17/23) developed acquired resistance, and 13.04% (3/23) had primary resistance. Using the specimens at the base-line, there was 1 (33.3%) patient with BCL2L11 loss (BIM deletion polymorphism), 1 (33.3%) patient with PTEN mutation, and 1 (33.3%) patient with KIT mutation. Median PFS was significantly shorter in patients with primary resistance than those with acquired resistance (2.3 vs. 14.5 months, P < 0.001). Conclusions: BCL2L11 loss, PTEN mutation, and KIT mutation might contribute to molecular mechanisms of primary resistance to crizotinib in ROS1þ NSCLC. Further investigations are warranted to overcome these primary resistances.