Efficacy and pattern failures of early SBRT to primary tumor in advanced EGFR mutation lung cancer (Target-SBRT): A single-arm phase 2 study.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e21130-e21130
Author(s):  
Dongqing Lv ◽  
Hailing Xu ◽  
Jiapei Ding ◽  
Ling Lin ◽  
Chao Zhou ◽  
...  
Keyword(s):  
Primary Tumor ◽  
Egfr Mutation ◽  
Advanced Nsclc ◽  
Radiation Pneumonitis ◽  
Combined Therapy ◽  
Progression Rate ◽  
Grade 3 ◽  
L858r Mutation ◽  
Tki Treatment ◽  
Egfr Tki

e21130 Background: It is evitable for advanced NSCLC harboring EGFR mutation with 1st TKI to develop resistance with 9-13 months of PFS and 19-27 months of OS. Initial progression of TKI treatment in NSCLC was 47.2% from the primary sites, 20.4% from the new sites and 32.6% from the primary and new sites. We hypothesized that early stereotactic body radiation therapy (SBRT) to primary tumor in advanced EGFR mutation NSCLC combined with EFGR-TKI treatment could prolong targeted resistance and explored its pattern failures. Methods: Eligible patients pathologically confirmed advanced NSCLC with Exon19 deletion or Exon21 L858R mutation were enrolled (ChiCTR-OIN-17013920). Each patient received EGFR TKI (Icotinib 125mg tid or gefitinib 250mg qd) and early SBRT (40-60 Gy/5-8F/5-10d) for primary tumor about 1 months from the beginning of EGFR TKI until disease progressed. Initial progression in sites of original disease (primary/metastatic) was defined as original site failure (OF) and appearance of new lesions as distant site failure (DF). Simultaneous OF/DF was labeled as ODF. The primary endpoint was PFS and the second endpoints were pattern failures, OS as well as adverse effects (AEs). Study was designed to enroll 50 patients to detect 6 months’ extension of PFS. Results: The study was closed after 41 patients enrolled due to the use of more effective 3rd EGFR-TKI.There were 37 PR and 4 SD after one month of TKI treatment and the average tumor shrinkage rate was 42.5%. The average interval from TKI to SBRT was 1.43 months (0.87-2.77 months). Median PFS and OS were 15.2 months (95% CI 13.1-17.4) and 27.6 months (95% CI 23.1-32.1), respectively. Of 37 patients who progressed, 6 (16.2%) had OF, 21 (56.8%) had DF, and 10 (27.0%) had ODF. The lung was the most common site of initial progression. As for toxicity, there was no ≥Grade 3 AEs and Grade 1-2 radiation Pneumonitis was the most frequent AEs. Conclusions: Early SBRT for primary tumor generated prolonged PFS without serious radiation pneumonitis in advanced EGFR mutation NSCLC patients with TKI treatment. This combined therapy obtained remarkably lower primary tumor progression rate and favorable OS. Clinical trial information: ChiCTR-OIN-17013920.

scholarly journals Efficacy and Acquired Resistance of EGFR-TKI Combined with Chemotherapy as First-Line Treatment for Chinese Patients with Advanced Non-Small Cell Lung Cancer in a Real-world Setting

2020 ◽  
Author(s):  
Qianqian Wang ◽  
Wen Gao ◽  
Fangyan Gao ◽  
Shidai Jin ◽  
Tianyu Qu ◽  
...  
Keyword(s):  
Egfr Mutation ◽  
Advanced Nsclc ◽  
Acquired Resistance ◽  
Small Cell ◽  
Combination Group ◽  
Monotherapy Group ◽  
Small Cell Lung ◽  
T790m Mutation ◽  
Nsclc Patients ◽  
Egfr Tki

Abstract Background To compare the benefits and explore the cause of acquired resistance of epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) and its combination with chemotherapy in advanced non-small-cell lung cancer (NSCLC) patients harboring EGFR mutation in a real-life setting.Methods This retrospective analysis included 117 advanced NSCLC patients with EGFR mutation who underwent next-generation sequencing (NGS) prior to treatment. The combination group included 50 patients who received the regimen of EGFR-TKI combined with chemotherapy, while the EGFR-TKI monotherapy group included 67 patients treated with TKI only. The primary endpoint of this study was progression-free survival (PFS); the secondary endpoints were overall survival (OS), response rate, and toxicity.Results The median PFS was significantly longer in the combination group than in the EGFR-TKI monotherapy group (19.00 months [95% CI, 14.674-23.326] vs. 11.70 months [95% CI, 10.807-12.593], p = 0.000). Subgroup analysis showed a similar trend of results. The median OS was not reached in the combination group and was 38.50 (95% CI, 35.300-41.700) months in the EGFR-TKI monotherapy group (p = 0.586). Patients in the combination group were more likely to experience adverse events, most of which showed the severity of grade 1 or 2. T790M mutation remains the main reason for acquired resistance, and the frequency of T790M mutation was similar between the two groups (p = 0.898). Conclusions Compared with EGFR-TKI monotherapy, EGFR-TKI combined with chemotherapy significantly improved PFS in advanced NSCLC patients with EGFR mutation, with acceptable toxicity.

scholarly journals P2.01-049 Long Progression Free Survival and Overall Survival in Advanced NSCLC Patients with EGFR Mutation and Complete Response with TKI Treatment

2017 ◽  
Vol 12 (11) ◽  
pp. S2088
Author(s):  
O. Macedo-Pérez ◽  
I. Lyra-González ◽  
D. Marroquín-Flores ◽  
G. Cruz-Rico ◽  
L. Ramírez-Tirado ◽  
...  
Keyword(s):  
Overall Survival ◽  
Egfr Mutation ◽  
Advanced Nsclc ◽  
Progression Free Survival ◽  
Complete Response ◽  
Free Survival ◽  
Tki Treatment ◽  
Nsclc Patients

Uncommon EGFR mutations associate with lower incidence of T790M mutation after EGFR-TKI treatment in patients with advanced NSCLC

Lung Cancer ◽  
2020 ◽  
Vol 139 ◽  
pp. 133-139 ◽  
Author(s):  
Shuo Yang ◽  
Shiqi Mao ◽  
Xuefei Li ◽  
Chao Zhao ◽  
Qian Liu ◽  
...  
Keyword(s):  
Lower Incidence ◽  
Advanced Nsclc ◽  
Egfr Mutations ◽  
T790m Mutation ◽  
Tki Treatment ◽  
Egfr Tki

Quantitative test of mutant EGFR and its effect on efficacy of EGFR TKI in advanced NSCLC.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e22186-e22186
Author(s):  
Caicun Zhou ◽  
Xuefei Li ◽  
Shengxiang Ren ◽  
Guohua Yang ◽  
Wei He
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Egfr Mutation ◽  
Advanced Nsclc ◽  
Progression Free Survival ◽  
Egfr Mutations ◽  
Conserved Sequence ◽  
Egfr Tki ◽  
Mutant Egfr

e22186 Background: It is reported that abundance of EGFR mutation is related with efficacy of EGFR TKI in advanced NSCLC patients with positive EGFR mutations. This study was designed to investigate influence of EGFR mutations and their abundance on efficacy of EGFR TKI. Methods: 141 advanced NSCLC treated with EGFR TKI and available tissue for EGFR mutations were enrolled into the study. EGFR mutation was detected with the kit of AmoyDx ARMS and concentration of mutant EGFR was detected with the method of a quantitative competitive allele specific Taqman PCR technology (qCAST). In this assay, copies from EGFR mutants were calibrated by standard curve respectively, and the mutation rates were estimated through normalizing by copies of a conserved sequence in EGFR exon2. The relationship between abundance of EGFR mutations and efficacy of EGFR TKI was analyzed. Results: The median age of patients was 59 years old, and in which 54.3% were male, 71.7% ex-somkers. Among all of the patients, adenocarcinoma accounted for 57.7%, squamous cell carcinoma 27.2%, adeno-squamous cell carcinoma 7.6%, and others 7.6%. 46.7% of patients harbored EGFR mutations, and in which 48.7% existed more than 20% abundance of EGFR mutations. Overall response rate was 31.4% and progression free survival was 5.0 months. The final analysis data will be reported at the conference. Conclusions: The abundance of EGFR mutations might affect the efficacy of EGFR-TKI, and quantitation of mutant EGFR may better predict for efficacy of EGFR TKI in advanced NSCLC.

Association Between EGFR T790M Status and Progression Patterns During Initial EGFR-TKI Treatment in Patients Harboring EGFR Mutation

2017 ◽  
Vol 18 (6) ◽  
pp. 698-705.e2 ◽  
Author(s):  
Yuko Oya ◽  
Tatsuya Yoshida ◽  
Hiroaki Kuroda ◽  
Junichi Shimizu ◽  
Yoshitsugu Horio ◽  
...  
Keyword(s):  
Egfr Mutation ◽  
Tki Treatment ◽  
Egfr Tki ◽  
Egfr T790m ◽  
Progression Patterns

scholarly journals First-Generation EGFR-TKI Plus Chemotherapy Versus EGFR-TKI Alone as First-Line Treatment in Advanced NSCLC With EGFR Activating Mutation: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

2021 ◽  
Vol 11 ◽  
Author(s):  
Qiang Wu ◽  
Wuxia Luo ◽  
Wen Li ◽  
Ting Wang ◽  
Lin Huang ◽  
...  
Keyword(s):  
First Generation ◽  
Egfr Mutation ◽  
Advanced Nsclc ◽  
Meta Analysis ◽  
Controlled Trials ◽  
Line Treatment ◽  
First Line ◽  
Randomized Controlled ◽  
Egfr Tki ◽  
First Line Treatment

ObjectiveThe aim of this meta-analysis was to evaluate efficacy and toxicity of epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) in combination with chemotherapy (CT) compared to EGFR-TKI monotherapy as first-line treatment in advanced non-small cell lung cancer (NSCLC) harboring activating EGFR mutation.MethodsA systematic literature search of randomized controlled trials using Cochrane Library, PubMed, Embase, and Web of Science, was performed up to Jan. 7th, 2020. Hazard ratios (HRs) with 95% confidence intervals (CI) were calculated as effect values for progress-free survival (PFS) and overall survival (OS). Risk ratio (RR) and Odds ratio (OR) were calculated as effect values for objective response rate (ORR) and toxicity, respectively.ResultsA total of eight randomized trials involving 1,349 advanced NSCLC patients with sensitive EGFR mutation were included in the meta-analysis. All patients in both groups received first-generation TKI as first-line treatment. The pooled HR of PFS and OS was 0.56 (95% CI = 0.50–0.64; P <0.00001) and 0.70 (95% CI = 0.54–0.90; P = 0.005), respectively. Subgroup analysis showed significantly higher OS advantages in patients receiving doublet CT (P = 0.02) and concurrent therapy (P = 0.002). The ORR in the EGFR-TKI plus CT group was significantly higher than in the EGFR-TKI monotherapy group (RR = 1.18, 95% CI = 1.10–1.26). The combination regimen showed a higher incidence of chemotherapy-induced toxicities. Subgroup analysis indicated that doublet chemotherapy rather than single-agent chemotherapy significantly increased incidence of grade 3 or higher leukopenia, neutropenia and anemia.ConclusionsCompared with EGFR-TKI monotherapy, the combination of first-generation EGFR-TKI and CT, especially when applying concurrent delivery of platinum-based doublet chemotherapeutic drugs, significantly improve ORR and prolong PFS and OS in first-line treatment for advanced EGFR-mutated NSCLC. Although increasing incidence of chemotherapy-induced toxicities occurs in the combination group, it is well tolerated and clinically manageable.

Concomitant pemetrexed/carboplatin chemotherapy with 3-D conformal radiotherapy followed by pemetrexed/carboplatin consolidation chemotherapy in locally advanced non-small cell lung cancer in a Chinese population

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e18502-e18502
Author(s):  
S. Ma ◽  
Y. Xu ◽  
X. Yu
Keyword(s):  
Lung Cancer ◽  
Chinese Population ◽  
Advanced Nsclc ◽  
Radiation Pneumonitis ◽  
Locally Advanced ◽  
Small Cell ◽  
Small Cell Lung ◽  
Locally Advanced Nsclc ◽  
Grade 3 ◽  
Carboplatin Auc

e18502 Background: Pemetrexed in combination with carboplatin has been shown to have promising activity, as well as superior toxicity profile in advanced non-small cell lung cancer(NSCLC). Radiotherapy(RT) has been shown to improve survival of patients with locally advanced NSCLC when combined with other platin doublets. This phase II study of concomitant pemetrexed/carboplatin chemotherapy(CT) with 3-D conformal RT followed by pemetrexed/carboplatin consolidation CT in locally advanced NSCLC was designed to evaluate the efficacy and safety of this novel regimen. This report presents preliminary information of 10 patients who have completed treatment. Methods: 10 chemoradiation (CRT)-naive and stage IIIA or IIIB (not effusion) with KPS≥80 patients were included in this study between February 2008 and October 2008. Patients received pemetrexed 500 mg/m2, carboplatin AUC 5 CT repeated q3 weeks for 2 cycles concomitant with RT and 3 cycles of consolidation pemetrexed (500 mg/m2) and carboplatin (AUC=5) q3 weeks. Median total dose of RT, without elective nodal irradiation, was 62 Gy (range: 60-66 Gy) with 2 Gy daily fractions. Results: 1 (10%) and 8 patients (80%) had a complete or partial response respectively, while 1 patient(10%) had progression of the disease(brain metastases). The overall response rate (90%,95% confidence interval (CI): 68%-97%) exceeded the goal per study design. After concomitant CRT, the main toxicity was neutropenia, with a median ANC nadir of 1.6, three patients had Grade 3 neutropenia, One patient had Grade 4 neutropenia. Grade 3 thrombocytopenia was seen in one patient, grade 3 esophagitis in one patient and grade 3 radiation pneumonitis in one patient. Consolidation CT was not administered to 3 patients- one due to the development of brain metastases during the first month after chemoradiation, one due to patient refusal and one due to grade 3 radiation pneumonitis. Conclusions: This preliminary data suggests that concomitant treatment was well tolerated, with promising activity and a significant improvement of QoL in a Chinese population with locally advanced NSCLC. No significant financial relationships to disclose.

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