scholarly journals Efficacy and Resistance of Afatinib in Chinese Non-Small Cell Lung Cancer Patients With HER2 Alterations: A Multicenter Retrospective Study

2021 ◽  
Vol 11 ◽  
Author(s):  
Zhengbo Song ◽  
Dongqing Lv ◽  
Shiqing Chen ◽  
Jianhui Huang ◽  
Liping Wang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Retrospective Study ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Progression Free Survival ◽  
Small Cell ◽  
Chinese Patients ◽  
Clinical Activity ◽  
Small Cell Lung ◽  
Nsclc Patients

BackgroundNon-small cell lung cancer (NSCLC) patients with HER2 mutations and amplification may benefit from HER2-targeted therapy, including afatinib. However, the data regarding the clinical activity of afatinib in Chinese patients with NSCLC harboring HER2 alterations are limited.Patients and methodsWe retrospectively included metastatic NSCLC patients harboring HER2 alterations who treated with afatinib. The clinical outcomes included overall response rate (ORR), progression-free survival (PFS) and overall survival (OS). The genomic profiling data after progression on afatinib were analyzed.ResultsWe included 54 patients harboring HER2 mutations and 12 patients harboring HER2 amplification. The ORR was 24% (95% CI, 16–36%), the median PFS was 3.3 months (95% CI, 2.2–4.4), and the median OS was 13.9 months (95% CI, 11.4–16.5). Patients with HER2 exon 20 mutations had numerically worse ORR (17% vs 42%), shorter PFS (2.6 vs 5.8 months, HR, 2.5; 95% CI, 1.2–5.5; P = 0.015) and OS (12.9 vs 33.3 months, HR, 4.4; 95% CI, 1.3–14.8; P = 0.009) than patients with other mutations. For HER2-amplified patients, the ORR was 33% (95% CI, 14–61%), the median PFS was 3.3 months (95% CI, 2.6–4.0), and the median OS was 13.4 months (95% CI, 0–27.6). The most frequently mutated genes in afatinib-resistant patients were TP53 (44%) and EGFR (33%). Three afatinib-resistant patients harbored secondary HER2 alterations.ConclusionsOur results suggest that afatinib has a promising anti-tumor activity in patients with NSCLC harboring HER2 alterations. To our knowledge, this is the largest retrospective study about the clinical activity of afatinib in NSCLC patients with HER2 alterations.

The targetable mutation landscape of Chinese patients with non-small cell lung cancer.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e13018-e13018
Author(s):  
Jun Li ◽  
Cuiyun Zhang ◽  
Jiuzhou Zhao ◽  
Zhizhong Wang ◽  
Bing Wei ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Kinase Inhibitors ◽  
Small Cell ◽  
Chinese Patients ◽  
Molecular Testing ◽  
Small Cell Lung ◽  
Essential Information ◽  
Nsclc Patients

e13018 Background: In recent years, the prognosis of non-small cell lung cancer (NSCLC) patients has been substantially improved by targeted therapies against specific molecular aberrations, i.e. tyrosine kinase inhibitors (TKIs) for Epidermal Growth Factor Receptor ( EGFR) etc. Several genes have been suggested by NCCN guideline (v7.2017) to test for NSCLC patients, including EGFR, ALK, ROS1, BRAF, MET, RET, HER2 and KRAS. The aim of this study is to profile the landscape of actionable mutations in Chinese NSCLC patients. Methods: From 2015 to 2017 621 treatment naïve NSCLC patients enrolled in the affiliated cancer hospital of Zhengzhou University were included in this analysis. DNA was extracted from the FFPE biopsies of these patients and processed for target capture sequencing covering the exons and flanking splicing regions of the 8 genes suggested by NCCN guideline, as well as introns of ROS, ALK and RET. Results: In total, 593 out of the 621 NSCLC patients harbor one or more mutations in these 8 genes, accounting for 95.5% of all the cases. EGFR, ALK and HER2 are the top 3 mutants, with a frequency of 52%, 32% and 26% respectively. Genetic aberrations in BRAF, MET, ROS1, KRAS and RET occur in 22%, 18%, 16% and 14% of the patients. The most common variation is missense; T > G, C > T and C > A changes are more often observed than T > C, T > A and C > G; the median number of variants per sample is 2, ranging from 1 to 13. There are 418 mutations detected on EGFR, of which 206 (49.28%) are clinically relevant. EGFR L858R, Exon19 deletion, Exon20 insertion, G719, A750P were observed in 123 (29.43%), 43 (10.29%), 8 (1.91%), 6 (1.44%) and 6 (1.44%) cases respectively. Gene fusions were identified in 78 cases, and the EML4- ALK is the most common one occurred in 54 patients, other fusion genes include KIF5B- ALK (11) ， CCDC6- RET (4), CD74- ROS1 (4), EZR- ROS1 (2), ERC1- RET (1), , SDC4- ROS1 (1) and TCOF1- ROS1 (1). Conclusions: Target sequencing of the 8 genes suggested by NCCN guideline for NSCLC patients reveals essential information for designing personalized therapeutic regimen. Chinese patients, maybe other Asian countries also, may benefit more from this molecular testing, because of the high occurrence of actionable mutations.

Impact of SWI/SNF complex mutations in patients with non-small cell lung cancer (NSCLC) treated with immune checkpoint inhibitors: Immuno-oncology biomarker study in LC-SCRUM-Japan (LC-SCRUM-IBIS).

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 9530-9530
Author(s):  
Kiyotaka Yoh ◽  
Shingo Matsumoto ◽  
Naoki Furuya ◽  
Kazumi Nishino ◽  
Shingo Miyamoto ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Clinical Outcomes ◽  
Cell Lung Cancer ◽  
Immune Checkpoint ◽  
Checkpoint Inhibitors ◽  
Progression Free Survival ◽  
Small Cell ◽  
Small Cell Lung ◽  
Nsclc Patients

9530 Background: The SWI/SNF chromatin remodeling complex is reported to be involved in sensitivity and resistance to immune checkpoint inhibitor (ICI). However, their role in non-small cell lung cancer (NSCLC) remains unclear. We examined the relationship between SWI/SNF complex mutations and clinical outcomes of ICI in patients with NSCLC. Methods: Of 1017 lung cancer patients enrolled in LC-SCRUM-IBIS, 350 patients were analyzable for whole-exome sequencing (WES). WES data were used to analyze the presence of mutations in 29 major subunits of the SWI/SNF complexes. ARID1A and SMARCA4 mutations were also evaluated in a targeted NGS panel (Oncomine comprehensive assay, OCA). PD-L1 expression by 22C3, tissue tumor mutational burden (tTMB) by WES, STK11 and KEAP1 mutations by WES or OCA were also assessed. Durable clinical benefit (DCB) including CR, PR and SD > 6 mos to ICI, progression-free survival (PFS) and overall survival (OS) were compared in status of each of SWI/SNF complex mutations and other factors. Results: At least one mutation in any subunits of the SWI/SNF complex was present in 28% of NSCLC patients. The most common mutated subcomplexes were SMARCA4 (12%), BAF (7%: ARID1A, 4%), non-canonical BAF (3%), PBAF (3%), and SMARCA2 (2%). Of 101 NSCLC patients treated with PD-1/PD-L1 inhibitors, SMARCA4 mutations tended to be associated with lower DCB (16 vs 31%) and shorter median PFS (1.9 vs 3.6 m) and OS (7.4 vs 18.1m). Patients with ARID1A mutations tended to have better clinical outcomes (DCB, 40 vs 28%) compared to those without mutations. No significant associations were found between PD-L1 expression and SMARCA4 or ARID1A mutations. Patients with STK11/KEAP1 mutations had lower rate of PD-L1 expression (TPS > 50%) (18% vs 48%, P = 0.03) and worse clinical outcomes (DCB, 6 vs 33%) compared to those without mutations. There was no significant association between a tTMB status and clinical outcome. Conclusions: SMARCA4 and ARID1A mutations appear to affect clinical outcomes of ICI in NSCLC patients. These findings indicate that SWI/SNF complex mutations may serve as a predictive biomarker for ICI in NSCLC patients.

Efficacy of afatinib in the clinical practice: Final results of the GIDEON study in EGFR mutated non-small cell lung cancer (NSCLC) in Germany.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e21636-e21636
Author(s):  
Wolfgang M. Brueckl ◽  
Martin Reck ◽  
Harald Schäfer ◽  
Cornelius Kortsik ◽  
Tobias Gaska ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Progression Free Survival ◽  
Small Cell ◽  
Small Cell Lung ◽  
Clinical Routine ◽  
Free Survival ◽  
Nsclc Patients ◽  
Egfr Mutated

e21636 Background: Afatinib is an irreversible ErbB family blocker, which is approved for the treatment of advanced non-small cell lung cancer (NSCLC) patients with activating EGFR mutations. Here we report the final results of the prospective non-interventional study (NIS) GIDEON, which was initiated to investigate the efficacy and tolerability of afatinib in the daily clinical routine in Germany. Methods: EGFR-mutated NSCLC patients were treated with afatinib according to label until progression, death or discontinuation. Efficacy (progression-free survival (PFS) rate at 12 months, objective response rate, ORR; disease control rate, DCR; progression-free survival, PFS and overall survival, OS) was prospectively assessed by investigators. Data about tolerability were collected during routine treatment. Results: In total, 161 patients were enrolled at 41 sites in Germany, 152 patients received at least one dose of afatinib (treated set; TS) and 146 patients were treated according to the protocol (PPS). The majority of patients for the entire TS had exon 19 deletions (64.5%), followed by L858R point mut. (22.4%) and uncommon mut. (exon 18-21 point mut.; 13.1%). The primary objective was PFS-rate at 12 months, which was 50.2% in the PPS. Median PFS amounted to 12.2 months. ORR and DCR were 74.6% and 91.5% in the PPS, respectively. Median OS was 30.4 months with 1- and 2-year survival rates of 79.1% and 57.7%, respectively. Among pat. with uncommon EGFR-mut., the 12-months PFS rate was 40.2% with a mPFS of 10.7 months. ORR and DCR were 83.3% and 91.7%, respectively. The most frequent documented adverse drug reactions (ADRs) were diarrhea and rash/acne with 13.8% and 7.2% of grade 3 but no grade 4 or higher. Conclusions: Afatinib is a standard therapy for patients with activating EGFR mut. in Germany. The final results of this prospective NIS confirm the robust clinical data for afatinib in the clinical routine setting, including patients with uncommon exon 18-21 point mutations. Clinical trial information: NCT02047903.

The value of prognostic factors in Chinese patients with small cell lung cancer: A retrospective study of 999 patients

2016 ◽  
Vol 12 (2) ◽  
pp. 433-447 ◽  
Author(s):  
Xuan Hong ◽  
Qingyong Xu ◽  
Zhaoyang Yang ◽  
Meng Wang ◽  
Fang Yang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Prognostic Factors ◽  
Retrospective Study ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Chinese Patients ◽  
Small Cell Lung

scholarly journals Low TIP30 Protein Expression is Associated with a High Risk of Metastasis and Poor Prognosis for Non-Small-Cell Lung Cancer

2019 ◽  
Vol 8 (1) ◽  
pp. 83 ◽  
Author(s):  
Chao-Ju Chen ◽  
Po-An Chou ◽  
Ming-Shyan Huang ◽  
Yu-Peng Liu
Keyword(s):  
Lung Cancer ◽  
Protein Expression ◽  
Small Cell Lung Cancer ◽  
Mrna Expression ◽  
Cell Lung Cancer ◽  
Poor Prognosis ◽  
Progression Free Survival ◽  
Small Cell ◽  
Small Cell Lung ◽  
Nsclc Patients

Non-small-cell lung cancer (NSCLC) is a deadly malignancy with a high prevalence worldwide. A reliable biomarker that can predict the prognosis is required to determine the therapeutic strategy. TIP30 was first identified as a tumor suppressor. A number of mechanistic studies indicated that the downregulation of TIP30 enhances the stemness, migration and survival of NSCLC cells. However, the clinical relevance of TIP30 for the prognosis of NSCLC is unknown. From a meta-analysis of public microarray datasets, we showed the upregulation of TIP30 mRNA expression was associated with worse overall survival of NSCLC patients, which contradicted the tumor suppressive role of TIP30. It is worth noting that the TIP30 mRNA expression was not correlated with its protein expression in 15 NSCLC cell lines. The results from the immunohistochemistry of a tissue microarray showed the downregulation of the TIP30 protein expression was associated with a higher risk of metastasis. In addition, the decrease in TIP30 protein was correlated with worse overall and progression-free survival of the NSCLC patients. Multivariate analysis suggested the loss of TIP30 protein was an independent factor to predict the poor prognosis of NSCLC. Our data indicated that TIP30 protein, not mRNA, would be a potential prognostic biomarker of NSCLC.

Association of MUC16 mutations with immunotherapy biomarkers in Chinese non-small cell lung cancer patients.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e21061-e21061
Author(s):  
Tao Han ◽  
Taiyan Guo ◽  
Xia You ◽  
Qianru He ◽  
Qin Zhang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cancer Patients ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Chinese Patients ◽  
Next Generation Sequencing Data ◽  
Small Cell Lung ◽  
Chinese Cohort ◽  
Nsclc Patients

e21061 Background: MUC16 is frequently mutated in non-small cell lung cancer (NSCLC). Previous studies showed MUC16 mutation were associated with TMB and prognostic outcome in gastric cancer patients and may benefits for patients with immunotherapy. Herein, we aimed to characterize the association of MUC16 with immunotherapy biomarkers in Chinese and Western NSCLC patients. Methods: Next-generation sequencing data and clinical data were collected from 1053 TCGA NSCLC patients (Western cohort). A 539-gene panel targeted sequencing assay was performed on FFPE tumor samples from 1056 Chinese pan-cancer patients (Chinese cohort). Both MUC16 mutation ratio and TMB were calculated on the two cohorts following the same criteria. Results: In total, 269 (25%) of the 1056 Chinese patients and 494 (47%) of the 1053 Western patients had at least one mutation of MUC16 genes ( MUC16 mutant group). The Chinese cohort had a higher mutation frequency of MUC16 gene than the Western cohort (25% vs. 47%, p＜0.001). In both cohorts, TMB was higher in the MUC16 mutant group compared to non- MUC16 mutant group. In Chinese cohort, PD-L1 positive was not associated with MUC16 mutation. However, patients with MUC16 mutation were not associated with prolonged survival in Western immunotherapy cohort. Conclusions: Our study provided a landscape of MUC16 mutations in a much larger Chinese NSCLC group, which could be a valuable complement to TCGA dataset. Both in Chinese and Western cohorts, the higher TMB in MUC16 mutant patients suggested potential efficacy from immunotherapy of MUC16 mutant group. A larger validation cohort of MUC16 mutant is required to confirm these findings in the further.

Analysis of immune-mediated reactions in patients with non-small cell lung cancer treated with nivolumab and its association with effectiveness

2021 ◽  
pp. 107815522110674
Author(s):  
Susana Cortijo-Cascajares ◽  
Ana Cristina Cercós-Lletí ◽  
Sara Ortiz-Pérez ◽  
José Manuel Caro-Teller ◽  
José Miguel Ferrari-Piquero
Keyword(s):  
Lung Cancer ◽  
Adverse Events ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Strong Predictor ◽  
Progression Free Survival ◽  
Small Cell ◽  
Small Cell Lung ◽  
Number Of Patients ◽  
Nsclc Patients

Objective To study immune-related adverse events (irAEs) in non-small cell lung cancer (NSCLC) patients treated with nivolumab, as well as to assess whether these reactions could be predictors of further effectiveness of therapy. Methods Retrospective, observational and longitudinal study. All NSCLC patients who received nivolumab between February 2015-May 2020 were included. In terms of safety, irAEs and their severity were registered and to evaluate the effectiveness, overall survival (OS) and progression free survival (PFS) were calculated. Results 75 patients were included. 32 patients (43%) were reported irAES. Mainly the irAEs affected the skin (36%). Followed by pneumonitis (20%), gastrointestinal reactions (12%), endocrine (12%) and hepatitis (12%). Regarding severity, 92% were moderate. The median PFS was 9.49 months on the group with irAEs versus 1.99 months on the group without irAEs group (p < 0.0001). The median OS was 17.44 months versus 7.67 months respectively (p = 0.0001). According to the incidence of irAEs developed ( = > 2 vs. 1 vs. 0), the median PFS was 20.53 versus 5.35 versus 1.99 months respectively (p < 0.0001). The median OS was 23.41 versus 15.80 versus 7.67 months, respectively (p = 0.0002) Conclusion In a significant number of patients irAEs occur, generally of grade 1–2 severity, affecting mainly the skin, lungs and gastrointestinal system. We confirm that the development of irAEs in patients with NSCLC treated with nivolumab is a strong predictor of treatment effectiveness in both PFS and OS, with statistically significant results. On those patients who experience two or more immunorelated adverse events the greatest benefit has been observed.

Sign in / Sign up

Export Citation Format

Share Document