scholarly journals Evaluation of the Effect of Proton Pump Inhibitors on the Efficacy of Dacomitinib and Gefitinib in Patients with Advanced Non-Small Cell Lung Cancer and EGFR-Activating Mutations

2021 ◽  
Author(s):  
Jerry Li ◽  
Dana Nickens ◽  
Keith Wilner ◽  
Weiwei Tan
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Proton Pump Inhibitors ◽  
Proton Pump ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Small Cell Lung ◽  
Activating Mutations

Association of proton pump inhibitors with survival in Veterans with non-small cell lung cancer receiving immunotherapy.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e18729-e18729
Author(s):  
William A. Stokes ◽  
Madhusmita Behera ◽  
Renjian Jiang ◽  
David Gutman ◽  
Felipe Giuste ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Proton Pump Inhibitors ◽  
Proton Pump ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Small Cell Lung ◽  
Comorbidity Burden ◽  
Nsclc Patients ◽  
The Impact

e18729 Background: Proton pump inhibitors (PPI) can disrupt the gut microbiome and thereby modulate response to immunotherapy in cancer patients. In a recently published post-hoc analysis of 757 non-small cell lung cancer (NSCLC) patients receiving atezolizumab pooled from two prospective trials, overall survival (OS) and progression-free survival were significantly lower among the 234 patients receiving PPI. We investigated the impact of PPI in a larger cohort of NSCLC patients treated with ICI within the Veterans Health Administration. Methods: We conducted a nested cohort study of Veterans who were diagnosed with NSCLC between 2010 & 2018 and treated with ICI (immune checkpoint inhibitors). Exposure was defined as receipt of a PPI prescription within 90 days of an ICI infusion. Chi-square tests were used to compare characteristics of exposed versus unexposed Veterans. OS was measured from start of ICI. Cox proportional hazard multivariate (MV) regression was used to calculate hazard ratios (HR) corresponding to variables associated with OS. Results: We identified 3,634 Veterans receiving ICI with non-exclusive exposures to nivolumab (59.3%), pembrolizumab (35.1%), durvalumab (6.9%), and atezolizumab (3.3%). Their median age was 69, and a plurality had male gender (97.0%), white race (73.0%), comorbidity count ≥1 (60.4%), adenocarcinoma (47.8%), and stage IV disease at diagnosis (40.9%). In this nested cohort, 2,159 (59.4%) were exposed to PPI, predominantly omeprazole (1,264 or 85.6% of PPI group). Patients receiving PPI were more likely to be ≤71 years of age, to be white, to reside in rural areas, to have a higher comorbidity burden, to have adenocarcinoma histology, and to receive chemotherapy (all p≤0.04). On MV analysis, PPI use was not significantly associated with detriment in OS (HR 0.96 [0.89-1.04], p= 0.35). In the matched cohort analysis, median survival did not significantly differ between the 1,389 patients taking PPI and the 1,389 without PPI (median 10 versus 10 months, HR 0.98 [0.90-1.06], p= 0.59). Conclusions: In the largest analysis to date of concurrent PPI use in patients with NSCLC receiving ICI, there were no survival differences associated with concomitant PPI use. These results suggest that PPIs do not compromise ICI efficacy.

scholarly journals Plasma Cell-Free DNA Testing of Patients With EGFR Mutant Non–Small-Cell Lung Cancer: Droplet Digital PCR Versus Next-Generation Sequencing Compared With Tissue-Based Results

2019 ◽  
pp. 1-9 ◽  
Author(s):  
Christi M.J. Steendam ◽  
Peggy Atmodimedjo ◽  
Evert de Jonge ◽  
Marthe S. Paats ◽  
Cor van der Leest ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Intraclass Correlation ◽  
Digital Pcr ◽  
Small Cell ◽  
Small Cell Lung ◽  
Activating Mutations ◽  
Activating Mutation ◽  
Pathology Specimen

PURPOSE To compare the results of plasma cell-free DNA (cfDNA) droplet digital PCR (ddPCR) and next-generation sequencing (NGS) on detection of epidermal growth factor receptor ( EGFR) primary activating mutations and p.T790M with results of tissue analysis in patients with EGFR mutated non–small-cell lung cancer. METHODS All patients with EGFR mutated non–small cell lung cancer for which a pathology and a plasma specimen were available upon progression between November 2016 and July 2018 were selected. Concordance, Cohen’s κ, and intraclass correlation coefficients were calculated. RESULTS Plasma cfDNA and pathology specimens of 36 patients were analyzed. Agreement between ddPCR and NGS was 86% (κ = 0.63) for the primary activating mutation and 94% (κ = 0.89) for the p.T790M detection. Allele ratios were comparable, with an intraclass correlation coefficient of 0.992 and 0.997, respectively. Discrepancies of some degree were found in 15 patients (41.7%). In six patients (16.7%), no mutations were detected in cfDNA. In three patients (8.3%), p.T790M was detected in plasma but not in the pathology specimen, whereas in three other patients (8.3%), p.T790M was demonstrated in the pathology specimen but not in plasma. Concordance of cfDNA and pathology for the primary activating mutation was 69% for ddPCR and 83% for NGS. For the detection of p.T790M, this was 75% (κ = 0.49) for ddPCR as well as for NGS. CONCLUSION Mutual agreement is high between NGS and ddPCR in cfDNA on the level of a specific mutation, with comparable ratio results. Plasma testing of EGFR primary activating mutations and p.T790M shows high concordance with pathology results, for NGS as well as for ddPCR, depending on the extent of the panel used. In NGS, more genetic aberrations can be investigated at once.

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