Correlation of gefitinib and its metabolites with gefitinib induced rash in patients with non-small cell lung cancer (NSCLC).

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e21712-e21712
Author(s):  
Shaoxing Guan ◽  
Xi Chen ◽  
Min Huang ◽  
Li Zhang ◽  
Xueding Wang
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Multivariate Logistic Regression Analysis ◽  
Small Cell ◽  
Therapeutic Drug ◽  
Small Cell Lung ◽  
Cutoff Values ◽  
Nsclc Patients ◽  
Severe Rash

e21712 Background: Gefitinib induced rash is the most common adverse reaction and severe rash of gefitinib often leads to discontinuation or termination of treatment. The concentrations of drug and its metabolites may affect drug induced toxicities, however, the association of gefitinib/metabolites with gefitinib-induced rash are poorly investigated. Therefore, we explored the association between concentrations of gefitinib and its four metabolites with gefitinib-induced rash in non-small cell lung cancer (NSCLC) patients. Methods: A total of 180 advanced NSCLC patients carrying EGFR sensitive mutations receiving gefitinib were enrolled. The concentrations of gefitinib, and its four metabolites including M537194, M387783, M523595 and M605211 were determined by liquid chromatography–tandem mass spectrometry (LC–MS/MS). The associations between concentration of gefitinib/its metabolites and gefitinib-induced rash were analyzed by Mann-Whiney U test. Operating characteristic curves(ROC) were used to determine gefitinib/metabolites cutoff values for gefitinib-induced rash. Results: M605211 was first detected in plasma in NSCLC patients. The concentrations of gefitinib and M605211, M537194 were found to be correlated with the incidence of gefitinib-induced rash ( P= 0.0002, 0.027 and 0.0097, respectively), moreover, the concentration of gefitinib was correlated with severe rash (Grade 0,1 vs. 2+, P= 0.017). Multivariate Logistic regression analysis showed that only gefitinib concentration was independent risk factor for gefitinib-induced rash (grade 0 vs grade1+, OR = 1.006, 95%CI (1.002-1.009), P = 0.00078; grade0,1 vs grade2+, OR = 1.003, 95%CI (1.001-1.005), P = 0.015, respectively). The cutoff values of gefitinib were 160.2 ng/ml (grade 0 vs grade1+, sensitivity = 78.7%, specificity = 47.7%, area under the curve (AUC) = 0.686, P = 0.0002, 95% CI (0.592-0.779)) and 201.7ng/ml (grade0,1 vs grade2+, sensitivity = 69.3%, specificity = 47.6%, AUC = 0.605, P = 0.0168, 95%CI (0.521-0.689)). Conclusions: This research demonstrated that the concentration of gefitinib and its metabolites were associated with gefitinib induced rash in NSCLC patients. Therapeutic drug monitoring of gefitinib concentration may have potential improvement for optimization of treatment with gefitinib. Clinical trial information: NCT01994057.

Initial safety and efficacy results of erlotinib in previously treated patients with advanced non-small cell lung cancer

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 18183-18183
Author(s):  
S. Zhou ◽  
C. Zhou ◽  
L. Yan ◽  
Q. Xu ◽  
J. Xu
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Smoking Status ◽  
Small Cell ◽  
Small Cell Lung ◽  
Significant Difference ◽  
Previously Treated ◽  
Nsclc Patients ◽  
Severe Rash

18183 Background: Erlotinib is an orally available selective HER1/EGFR tyrosine kinase inhibitor. In the BR.21 trial, erlotinib significantly improved survival and quality of life in non-small cell lung cancer(NSCLC) patients (pts). The study evaluated the initial efficacy and safety of erlotinib in previously treated advanced or metastatic NSCLC patients in Shanghai, China. Methods: Eligibility criteria included stage IIIb/IV or recurrent NSCLC pts who failed from prior chemotherapy, PS = 0–2, weight loss less than 5%, and no urgent symptoms. Pts received oral erlotinib 150 mg po/day until objective or symptomatic progression. Results: 50 pts were enrolled from Oct 1 to Sept 30. Demographics: M 68%/F 32%; median age 55 y [range 28–68]; stage IV 86%; PS 0/1/2:2 (4%)/44 (88%)/4 (8%); adenocarcinoma/non-adenocarcinoma 39 (78%)/11 (22%); smoking status: 26 (52%) /no 24 (48%). The major toxicity was rash: 48 (96%), 10 (20%) of them are grade 3/4; other toxicity included grade 1/2 diahhrea: 5 (10%); grade 1/2 liver dysfunction: 4 (8%); grade 2 leucocytopenia: 2 (4%); grade 1 thrombocytopenia: 1(2%); fatigue and dyspnea. 3 patients discontinued for dyspnea, pneumonitis and fatigue respectively. No pts had pulmonary fibrosis and dose reduction. 47 pts were followed long enough for efficacy evaluation, which indentified 18 (38%) with PR, 21 (45%) with SD, 8 (17%) with PD. Subgroup analysis showed the resposes to erlotinib have no relation with gender, age, smoking status, performance status, histology and stages, however, significant difference existed in the subgroup patients with severe rash and less symptoms such as dyspnea and fatigue ( Table 1 ). Conclusions: Erlotinib is active and well tolerated in patients with advanced NSCLC failed to previously chemotherapy. Preliminary results suggest patients with severe rash, less dyspnea and fatigue are accociated with better response. The study in ongoing. Table 1 Response of erlotinib in advanced treated NSCLC pts. * P values less than 0.05. [Table: see text] No significant financial relationships to disclose.

scholarly journals Biomarkers and Gene Signatures to Predict Durable Response to Pembrolizumab in Non-Small Cell Lung Cancer

Cancers ◽  
2021 ◽  
Vol 13 (15) ◽  
pp. 3828
Author(s):  
Anello Marcello Poma ◽  
Rossella Bruno ◽  
Iacopo Pietrini ◽  
Greta Alì ◽  
Giulia Pasquini ◽  
...  
Keyword(s):  
Lung Cancer ◽  
T Cells ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Immune Cell ◽  
Small Cell ◽  
Small Cell Lung ◽  
First Line ◽  
Durable Response ◽  
Nsclc Patients

Pembrolizumab has been approved as first-line treatment for advanced Non-small cell lung cancer (NSCLC) patients with tumors expressing PD-L1 and in the absence of other targetable alterations. However, not all patients that meet these criteria have a durable benefit. In this monocentric study, we aimed at refining the selection of patients based on the expression of immune genes. Forty-six consecutive advanced NSCLC patients treated with pembrolizumab in first-line setting were enrolled. The expression levels of 770 genes involved in the regulation of the immune system was analysed by the nanoString system. PD-L1 expression was evaluated by immunohistochemistry. Patients with durable clinical benefit had a greater infiltration of cytotoxic cells, exhausted CD8, B-cells, CD45, T-cells, CD8 T-cells and NK cells. Immune cell scores such as CD8 T-cell and NK cell were good predictors of durable response with an AUC of 0.82. Among the immune cell markers, XCL1/2 showed the better performance in predicting durable benefit to pembrolizumab, with an AUC of 0.85. Additionally, CD8A, CD8B and EOMES showed a high specificity (>0.86) in identifying patients with a good response to treatment. In the same series, PD-L1 expression levels had an AUC of 0.61. The characterization of tumor microenvironment, even with the use of single markers, can improve patients’ selection for pembrolizumab treatment.

scholarly journals Circulating Biomarkers of Response and Toxicity of Immunotherapy in Advanced Non-Small Cell Lung Cancer (NSCLC): A Comprehensive Review

Cancers ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1794
Author(s):  
Alice Indini ◽  
Erika Rijavec ◽  
Francesco Grossi
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Liquid Biopsy ◽  
Cytotoxic T Lymphocyte ◽  
Checkpoint Inhibitors ◽  
Small Cell ◽  
Circulating Biomarkers ◽  
Small Cell Lung ◽  
Nsclc Patients

Immune checkpoint inhibitors (ICIs) targeting the programmed cell death (PD)-1 protein and its ligand, PD-L1, and cytotoxic T-lymphocyte-associated antigen (CTLA)-4, have revolutionized the management of patients with advanced non-small cell lung cancer (NSCLC). Unfortunately, only a small portion of NSCLC patients respond to these agents. Furthermore, although immunotherapy is usually well tolerated, some patients experience severe immune-related adverse events (irAEs). Liquid biopsy is a non-invasive diagnostic procedure involving the isolation of circulating biomarkers, such as circulating tumor cells (CTC), cell-free DNA (cfDNA), and microRNAs (miRNAs). Thanks to recent advances in technologies, such as next-generation sequencing (NGS) and digital polymerase chain reaction (dPCR), liquid biopsy has become a useful tool to provide baseline information on the tumor, and to monitor response to treatments. This review highlights the potential role of liquid biomarkers in the selection of NSCLC patients who could respond to immunotherapy, and in the identification of patients who are most likely to experience irAEs, in order to guide improvements in care.

scholarly journals 1318P Association between soluble PD-L1 and prognosis of non-small cell lung cancer (NSCLC) patients treated with immunotherapy

2020 ◽  
Vol 31 ◽  
pp. S851
Author(s):  
C. Dellepiane ◽  
S. Coco ◽  
M.G. Dal Bello ◽  
G. Rossi ◽  
E. Rijavec ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Small Cell Lung ◽  
Nsclc Patients

scholarly journals Molecular profile of KRAS G12C-mutant colorectal and non-small-cell lung cancer

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Luiz Henrique Araujo ◽  
Bianca Mendes Souza ◽  
Laura Rabelo Leite ◽  
Sabrina A. F. Parma ◽  
Natália P. Lopes ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Driver Mutations ◽  
Molecular Profile ◽  
Common Mutation ◽  
Small Cell Lung ◽  
The South ◽  
Nsclc Patients

Abstract Background KRAS is the most frequently mutated oncogene in cancer, however efforts to develop targeted therapies have been largely unsuccessful. Recently, two small-molecule inhibitors, AMG 510 and MRTX849, have shown promising activity in KRAS G12C-mutant solid tumors. The current study aims to assess the molecular profile of KRAS G12C in colorectal (CRC) and non-small-cell lung cancer (NSCLC) tested in a clinical certified laboratory. Methods CRC and NSCLC samples submitted for KRAS testing between 2017 and 2019 were reviewed. CRC samples were tested for KRAS and NRAS by pyrosequencing, while NSCLC samples were submitted to next generation sequencing of KRAS, NRAS, EGFR, and BRAF. Results The dataset comprised 4897 CRC and 4686 NSCLC samples. Among CRC samples, KRAS was mutated in 2354 (48.1%). Most frequent codon 12 mutations were G12D in 731 samples (14.9%) and G12V in 522 (10.7%), followed by G12C in 167 (3.4%). KRAS mutations were more frequent in females than males (p = 0.003), however this difference was exclusive of non-G12C mutants (p < 0.001). KRAS mutation frequency was lower in the South and North regions (p = 0.003), but again KRAS G12C did not differ significantly (p = 0.80). In NSCLC, KRAS mutations were found in 1004 samples (21.4%). As opposed to CRC samples, G12C was the most common mutation in KRAS, in 346 cases (7.4%). The frequency of KRAS G12C was higher in the South and Southeast regions (p = 0.012), and lower in patients younger than 50 years (p < 0.001). KRAS G12C mutations were largely mutually exclusive with other driver mutations; only 11 NSCLC (3.2%) and 1 CRC (0.6%) cases had relevant co-mutations. Conclusions KRAS G12C presents in frequencies higher than several other driver mutations, and may represent a large volume of patients in absolute numbers. KRAS testing should be considered in all CRC and NSCLC patients, independently of clinical or demographic characteristics.

scholarly journals Automated tumor proportion scoring for PD-L1 expression based on multistage ensemble strategy in non-small cell lung cancer

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Boju Pan ◽  
Yuxin Kang ◽  
Yan Jin ◽  
Lin Yang ◽  
Yushuang Zheng ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Image Analysis ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Automated Image Analysis ◽  
Small Cell Lung ◽  
Cutoff Values ◽  
Scoring Algorithm ◽  
Better Than

Abstract Introduction Programmed cell death ligand-1 (PD-L1) expression is a promising biomarker for identifying treatment related to non-small cell lung cancer (NSCLC). Automated image analysis served as an aided PD-L1 scoring tool for pathologists to reduce inter- and intrareader variability. We developed a novel automated tumor proportion scoring (TPS) algorithm, and evaluated the concordance of this image analysis algorithm with pathologist scores. Methods We included 230 NSCLC samples prepared and stained using the PD-L1(SP263) and PD-L1(22C3) antibodies separately. The scoring algorithm was based on regional segmentation and cellular detection. We used 30 PD-L1(SP263) slides for algorithm training and validation. Results Overall, 192 SP263 samples and 117 22C3 samples were amenable to image analysis scoring. Automated image analysis and pathologist scores were highly concordant [intraclass correlation coefficient (ICC) = 0.873 and 0.737]. Concordances at moderate and high cutoff values were better than at low cutoff values significantly. For SP263 and 22C3, the concordances in squamous cell carcinomas were better than adenocarcinomas (SP263 ICC = 0.884 vs 0.783; 22C3 ICC = 0.782 vs 0.500). In addition, our automated immune cell proportion scoring (IPS) scores achieved high positive correlation with the pathologists TPS scores. Conclusions The novel automated image analysis scoring algorithm permitted quantitative comparison with existing PD-L1 diagnostic assays and demonstrated effectiveness by combining cellular and regional information for image algorithm training. Meanwhile, the fact that concordances vary in different subtypes of NSCLC samples, which should be considered in algorithm development.

scholarly journals Metabolic Parameters as Biomarkers of Response to Immunotherapy and Prognosis in Non-Small Cell Lung Cancer (NSCLC): A Real World Experience

Cancers ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 1634
Author(s):  
Lavinia Monaco ◽  
Maria Gemelli ◽  
Irene Gotuzzo ◽  
Matteo Bauckneht ◽  
Cinzia Crivellaro ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Checkpoint Inhibitors ◽  
Complete Response ◽  
Metabolic Tumor Volume ◽  
Small Cell ◽  
Whole Body ◽  
Small Cell Lung ◽  
Nsclc Patients

Immune-checkpoint inhibitors (ICIs) have been proven to have great efficacy in non-small cell lung cancer (NSCLC) as single agents or in combination therapy, being capable to induce deep and durable remission. However, severe adverse events may occur and about 40% of patients do not benefit from the treatment. Predictive factors of response to ICIs are needed in order to customize treatment. The aim of this study is to evaluate the correlation between quantitative positron emission tomography (PET) parameters defined before starting ICI therapy and responses to treatment and patient outcome. We retrospectively analyzed 92 NSCLC patients treated with nivolumab, pembrolizumab or atezolizumab. Basal PET/computed tomography (CT) scan parameters (whole-body metabolic tumor volume—wMTV, total lesion glycolysis—wTLG, higher standardized uptake volume maximum and mean—SUVmax and SUVmean) were calculated for each patient and correlated with outcomes. Patients who achieved disease control (complete response + partial response + stable disease) had significantly lower MTV median values than patients who had not (progressive disease) (77 vs. 160.2, p = 0.039). Furthermore, patients with MTV and TLG values lower than the median values had improved OS compared to patients with higher MTV and TLG (p = 0.03 and 0.05, respectively). No relation was found between the other parameters and outcome. In conclusion, baseline metabolic tumor burden, measured with MTV, might be an independent predictor of treatment response to ICI and a prognostic biomarker in NSCLC patients.

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