scholarly journals Overlap time is an independent risk factor of radiation pneumonitis for patients treated with simultaneous EGFR-TKI and thoracic radiotherapy

2021 ◽  
Author(s):  
Wenxiao Jia ◽  
Qianqian Gao ◽  
Min Wang ◽  
Ji Li ◽  
Wang Jing ◽  
...  
Keyword(s):  
Risk Factors ◽  
First Generation ◽  
Kinase Inhibitors ◽  
Radiation Pneumonitis ◽  
Cell Cancer ◽  
Treatment Strategies ◽  
Thoracic Radiotherapy ◽  
Ipsilateral Lung ◽  
Nsclc Patients ◽  
Egfr Tki

Abstract Background: The exact rate and relevant risk factors of radiation pneumonitis (RP) for non-small-cell cancer (NSCLC) patients treated with the combination of epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) and thoracic radiotherapy have not been reported. Thus, this study aimed to investigate the rate and risk factors of RP for EGFR-positive NSCLC patients simultaneously treated with first-generation EGFR-TKI and TRT.Patients and Methods: We retrospectively evaluated NSCLC patients simultaneously treated with first-generation EGFR-TKI and thoracic radiotherapy between January 2012 and December 2019 at Shandong Cancer Hospital and Institute, Shandong, China. RP was diagnosed via computed tomography and was classified according to the Common Terminology Criteria for Adverse Events v5.0. The risk factors of RP were identified using uni- and multivariate analyses.Results: Of the 67 patients included, 44.78% (30/67) developed grade ≥2 RP. Grade ≥2 RP occurred within a median of 3.48 (range, 1.07-13.6) months. The EGFR-TKI icotinib, ipsilateral lung V30 >34%, and overlap time of >20 days between EGFR-TKI and thoracic radiotherapy were identified to be independent predictive factors of grade ≥2 RP.Conclusions: Grade ≥2 RP is highly frequent in NSCLC patients simultaneous treated with first-generation EGFR-TKI and thoracic radiotherapy. Icotinib, ipsilateral lung V30 ≤34%, and overlap time of ≤20 days for EGFR-TKI and thoracic radiotherapy will be helpful to lower the risk of RP in these patients. The addition of thoracic radiotherapy should be cautious, and the treatment strategies can be optimized to reduce the rate of RP for patients treat with simultaneous EGFR-TKI and thoracic radiotherapy.

scholarly journals Overlap time is an independent risk factor of radiation pneumonitis for patients treated with simultaneous EGFR-TKI and thoracic radiotherapy

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Wenxiao Jia ◽  
Qianqian Gao ◽  
Min Wang ◽  
Ji Li ◽  
Wang Jing ◽  
...  
Keyword(s):  
Risk Factors ◽  
First Generation ◽  
Kinase Inhibitors ◽  
Radiation Pneumonitis ◽  
Cell Cancer ◽  
Treatment Strategies ◽  
Thoracic Radiotherapy ◽  
Ipsilateral Lung ◽  
Nsclc Patients ◽  
Egfr Tki

Abstract Background The exact rate and relevant risk factors of radiation pneumonitis (RP) for non-small-cell cancer (NSCLC) patients treated with the combination of epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) and thoracic radiotherapy have not been reported. Thus, this study aimed to investigate the rate and risk factors of RP for EGFR-positive NSCLC patients simultaneously treated with first-generation EGFR-TKI and TRT. Patients and methods We retrospectively evaluated NSCLC patients simultaneously treated with first-generation EGFR-TKI and thoracic radiotherapy between January 2012 and December 2019 at Shandong Cancer Hospital and Institute, Shandong, China. RP was diagnosed via computed tomography and was classified according to the Common Terminology Criteria for Adverse Events v5.0. The risk factors of RP were identified using uni- and multivariate analyses. Results Of the 67 patients included, 44.78% (30/67) developed grade ≥ 2 RP. Grade ≥ 2 RP occurred within a median of 3.48 (range 1.07–13.6) months. The EGFR-TKI icotinib, ipsilateral lung V30 > 34%, and overlap time of > 20 days between EGFR-TKI and thoracic radiotherapy were identified to be independent predictive factors of grade ≥ 2 RP. Conclusions Grade ≥ 2 RP is highly frequent in NSCLC patients simultaneous treated with first-generation EGFR-TKI and thoracic radiotherapy. Icotinib, ipsilateral lung V30 ≤ 34%, and overlap time of ≤ 20 days for EGFR-TKI and thoracic radiotherapy will be helpful to lower the risk of RP in these patients. The addition of thoracic radiotherapy should be cautious, and the treatment strategies can be optimized to reduce the rate of RP for patients treat with simultaneous EGFR-TKI and thoracic radiotherapy.

scholarly journals Overlap Time is An Independent Risk Factor of Radiation Pneumonitis for Patients Treated With Simultaneous EGFR-TKI and Thoracic Radiotherapy

2020 ◽  
Author(s):  
Wenxiao Jia ◽  
Qianqian Gao ◽  
Min Wang ◽  
Ji Li ◽  
Wang Jing ◽  
...  
Keyword(s):  
Risk Factors ◽  
First Generation ◽  
Kinase Inhibitors ◽  
Radiation Pneumonitis ◽  
Cell Cancer ◽  
Treatment Strategies ◽  
Thoracic Radiotherapy ◽  
Ipsilateral Lung ◽  
Nsclc Patients ◽  
Egfr Tki

Abstract Background: The exact rate and relevant risk factors of radiation pneumonitis (RP) for non-small-cell cancer (NSCLC) patients treated with the combination of epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) and thoracic radiotherapy have not been reported. Thus, this study aimed to investigate the rate and risk factors of RP for EGFR-positive NSCLC patients simultaneously treated with first-generation EGFR-TKI and TRT.Patients and Methods: We retrospectively evaluated NSCLC patients simultaneously treated with first-generation EGFR-TKI and thoracic radiotherapy between January 2012 and December 2019 at Shandong Cancer Hospital and Institute, Shandong, China. RP was diagnosed via computed tomography and was classified according to the Common Terminology Criteria for Adverse Events v5.0. The risk factors of RP were identified using uni- and multivariate analyses.Results: Of the 67 patients included, 44.78% (30/67) developed grade ≥2 RP. Grade ≥2 RP occurred within a median of 3.48 (range, 1.07-13.6) months. The EGFR-TKI icotinib, ipsilateral lung V30 >34%, and overlap time of >20 days between EGFR-TKI and thoracic radiotherapy were identified to be independent predictive factors of grade ≥2 RP.Conclusions: Grade ≥2 RP is highly frequent in NSCLC patients simultaneous treated with first-generation EGFR-TKI and thoracic radiotherapy. Icotinib, ipsilateral lung V30 <34%, and shorter overlap time of <20 days for EGFR-TKI and thoracic radiotherapy will help lower the risk of RP in these patients. The addition of thoracic radiotherapy should be cautious, and the treatment strategies can be optimized to reduce the rate of RP for patients treat with simultaneous EGFR-TKI and thoracic radiotherapy.

scholarly journals Thoracic radiotherapy and concurrent almonertinib for unresectable stage III EGFR-mutated non-small-cell lung cancer: a phase 2 study

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Lucheng ZHU ◽  
Changlin Zou ◽  
Zhanchun Zhang ◽  
Jianfang Wang ◽  
Li Yang ◽  
...  
Keyword(s):  
Radiation Pneumonitis ◽  
Locally Advanced ◽  
Phase 2 ◽  
Thoracic Radiotherapy ◽  
Small Cell Lung ◽  
Unresectable Stage ◽  
Phase 2 Study ◽  
Nsclc Patients ◽  
Egfr Mutated ◽  
Egfr Tki

Abstract Background Concurrent chemo-radiotherapy remains the standard treatment in unresectable stage III non-small-cell lung cancer (NSCLC) patients. Several studies have shown a potential value of concurrent epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) with thoracic radiotherapy in EGFR-mutated population, but a high risk of radiation pneumonitis raised a major concern. This study intends to explore the safety and efficacy of concurrent almonertinib, a new third-generation EGFR-TKI, with radiotherapy in locally advanced EGFR-mutated NSCLC patients. Methods Locally advanced NSCLC patients harboring sensitive EGFR mutation will be included in this study. A radiotherapy plan will be made for each patient before treatment, and the lung V20 will be calculated. Patients with lung V20 ≥ 28% were enrolled in induction group (arm A), which almonertinib was given for 2 months followed by concurrent radiotherapy; patients with lung V20 < 28% were enrolled in concurrent group (arm B), which almonertinib was given concurrent with thoracic radiotherapy. The primary endpoint is the incidence of grade ≥ 3 radiation pneumonitis within 6 months post-radiotherapy, and the secondary endpoints are local control rate, progression-free survival, and overall survival. Discussion The safety and efficacy of third-generation EGFR-TKI concurrent with thoracic radiotherapy in locally advanced EGFR-mutated NSCLC is still unknown. We propose to conduct this phase 2 study evaluating the safety especially the radiation pneumonitis within 6 months post-radiotherapy. This trial protocol has been approved by the Ethics committee of Hangzhou cancer hospital. The ethics number is HZCH-2020-030. Trial registration clinicaltrials.gov, NCT04636593. Registered 19 November 2020 - Retrospectively registered

scholarly journals Co-Occurring Potentially Actionable Oncogenic Drivers in Non-Small Cell Lung Cancer

2021 ◽  
Vol 11 ◽  
Author(s):  
Yiming Zhao ◽  
Shuyuan Wang ◽  
Zhengyu Yang ◽  
Yu Dong ◽  
Yanan Wang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
First Generation ◽  
Kinase Inhibitors ◽  
De Novo ◽  
Treatment Strategies ◽  
Small Cell ◽  
Small Cell Lung ◽  
Nsclc Patients

BackgroundSeveral oncogenic drivers in non-small cell lung cancer (NSCLC) are considered actionable with available or promising targeted therapies. Although targetable drivers rarely overlap with each other, there were a minority of patients harboring co-occurring actionable oncogenic targets, whose clinical characteristics and prognosis are not yet clear.MethodsA total of 3,077 patients with NSCLC who underwent molecular analysis by NGS were included, and their demographic and clinical data were retrospectively collected.ResultsOur study found that the frequency of NSCLC patients harboring co-occurring potentially actionable alterations was approximately 1.5% (46/3077); after excluding patients with EGFR-undetermined mutations, the incidence was 1.3% (40/3077); 80% (37/46) harbored both EGFR mutations and other potentially actionable drivers such as MET amplification (21.6%; 8/37) and alterations in ERBB2 including mutations (27%; 10/37) and amplification (21.6%; 8/37); other combinations of potentially actionable drivers including alterations in ERBB2, KRAS, MET, ALK, and RET were also identified. Additionally, de novo MET/ERBB2 amplification in patients harboring EGFR-mutant NSCLC treated with first-generation EGFR tyrosine kinase inhibitors (TKIs) was associated with shorter PFS (p &lt; 0.05). The efficacy of TKIs in NSCLC patients harboring other co-occurring potentially actionable drivers varied across different molecular subtypes.ConclusionsApproximately 1.5% of NSCLCs harbored co-occurring potentially actionable oncogenic drivers, commonly involving EGFR mutations. Co-occurring actionable targets may impact the efficacy of TKIs; therefore, future clinical trials in these patients should be anticipated to tailor the combination or sequential treatment strategies.

Exon-16-skipping ERBB2 (ERBB2ΔEx16) as a novel resistance mechanism against EGFR tyrosine kinase inhibitors in non-small cell lung cancer (NSCLC).

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 9528-9528
Author(s):  
Xin Zhao ◽  
Linling Jin ◽  
Man Yu ◽  
Qiuxiang Ou ◽  
Hua Bao ◽  
...  
Keyword(s):  
Kinase Inhibitors ◽  
Small Cell ◽  
Large Fragment ◽  
Small Cell Lung ◽  
Egfr Tyrosine Kinase Inhibitors ◽  
Nsclc Patients ◽  
Egfr Mutated ◽  
Egfr Tki ◽  
Egfr T790m ◽  
Erbb2 Amplification

9528 Background: In addition to ERBB2 amplification/protein overexpression, activating ERBB2 alterations have been increasingly discovered in diverse human cancers with varying incidence. ERBB2ΔEx16 is an alternatively spliced isoform of ERBB2, lacking the entire exon 16 which encodes a small extracellular domain. ERBB2ΔEx16 was recently reported to lead to oncogenic activation of ERBB2 and osimertinib resistance in EGFR T790M+ non-small cell lung cancer (NSCLC). Methods: A total of 38,680 Chinese cancer patients whose tumor specimen or circulating cell-free DNA underwent genomic profiling by targeted next-generation sequencing of cancer-related genes were retrospectively reviewed. Clinicopathological features and treatment history of ERBB2ΔEx16+ patients were evaluated. RNA sequencing was performed to validate the presence of exon-16-skipping ERBB2 at the transcriptional level. Results: A total of eighteen ERBB2ΔEx16+ patients (11 NSCLC, 2 colorectal cancer, 2 gastric cancer, and 3 others) were identified (0.047%, 18/38,680). ERBB2 exon 16 skipping may result from large fragment deletion spanning the whole or partial region of exon 16 (72.2%, 13/18), base substitution at the splice acceptor site (16.7%, 3/18) and deletion of the splice donor site (11.1%, 2/18). ERBB2 exon 16 skipping, including large fragment deletion and splice site deletion, was validated at the RNA level by RNA sequencing in 3 patients with available samples. Co-occurrence of ERBB2 amplification and ERBB2 mutations were found in 83.3% (15/18) and 50% (9/18) of cases, respectively. Concurrent copy number variations were prevalent in CDK12 (55.6%, 10/18), CDKN2B (44.4%, 8/18), NKX2.1 (38.9%, 7/18) and PTPRD (33.3%, 6/18). Among the 11 cases of ERBB2ΔEx16+ NSCLC, 9 had coexisting activating EGFR mutations (exon 19 deletions, exon 21 L858R) and received prior treatment with EGFR tyrosine kinase inhibitors (TKIs), with 2 harboring acquired EGFR T790M mutation and 1 EGFR copy number gain. Further analysis of the matched pretreatment samples in 3 EGFR-mutated NSCLC patients confirmed that ERBB2ΔEx16 was acquired during EGFR TKI therapy. In the 7 cases of other cancers, 4 to 31 non- ERBB2 mutations were identified in each sample, with TP53 being the most frequently mutated gene. Conclusions: Our data suggest that ERBB2ΔEx16 may be a general mechanism of EGFR TKI resistance in a subset of EGFR-mutated NSCLC patients, in addition to being an oncogenic driver as reported in some solid malignancies including colorectal, gastric and ovarian cancers.

Molecular characteristics of EGFR exon 20 uncommon R776H mutation and response to osimertinib in NSCLC patients.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e21001-e21001
Author(s):  
Gaili An ◽  
Li He ◽  
Xifang Wang ◽  
Yu Lei ◽  
Dejian Gu ◽  
...  
Keyword(s):  
First Generation ◽  
Cell Clone ◽  
Progression Free Survival ◽  
Molecular Characteristics ◽  
Treatment Naïve ◽  
Tki Treatment ◽  
Exon 20 ◽  
Nsclc Patients ◽  
Ngs Data ◽  
Egfr Tki

e21001 Background: EGFR R776H is an uncommon exon 20 mutation in non-small cell lung cancer (NSCLC) patients. This mutation was first reported in samples after first generation EGFR TKI treatment as an acquired resistant mutation to first generation of EGFR-TKI. We further analyzed the molecular characteristics of patients with EGFR R776H mutation and its correlation with EGFR TKI therapy. Methods: In this study, a total of 16131 NSCLC patients from multiple centers with NGS data were retrospectively analyzed to study the molecular characteristics and clinical outcomes of patients with EGFR R776H mutation. Results: 44 of the 16131 patients (0.27%) had EGFR R776H mutation, and 28 of them (63.6%) were treatment-naïve while performing the mutation test. TP53 was the most common concomitant mutation in both treatment-naïve (57.1%) and treated (81.3%) patients. EGFR R776H mutation was found to coexist with multiple types EGFR mutation. The common mutations were EGFR L858R (54%) and EGFR G719A/S (25%), but It almost never coexists with 19del (2%). The coexist of EGFR R776H mutation was similar in both treatment-naïve and treated patients. In 16 of treated patients, all had received first - or second-generation EGFR TKI treatment, and the median progression-free survival (PFS) was 9 months. Interestingly, four of them found the presence of not only EGFR R776H but also EGFR T790M. It may be that EGFR R776H and T790M appear together in drug resistance, or it may be that EGFR R776H and EGFR sensitive mutation are not in the same cell clone. Two patients with EGFR R776H received treatment of Osimertinib and achieved partial response. The PFS of two patients in Osimertinib were 11 and 10 months, respectively. Moreover, EGFR C797S mutation was detected in two patients after resistant to Osimertinib. Conclusions: Presence of EGFR R776H mutation was rare in NSCLC patients and our retrospective study provides clinical evidence that Osimertinib could be of benefit and may potentially be an effective treatment strategy to improve survival outcomes in patients with EGFR R776H.

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