scholarly journals P48.12 Concurrent Chemotherapy and First-Generation EGFR-TKI as First-Line Treatment in Advanced Lung Adenocarcinoma Harboring EGFR Mutation

2021 ◽  
Vol 16 (10) ◽  
pp. S1111
Author(s):  
Z. Xu ◽  
X. Hao ◽  
L. Lin ◽  
J. Li ◽  
P. Xing
Keyword(s):  
Lung Adenocarcinoma ◽  
First Generation ◽  
Egfr Mutation ◽  
Concurrent Chemotherapy ◽  
Line Treatment ◽  
First Line ◽  
Egfr Tki ◽  
First Line Treatment

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.

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

2020 ◽  
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

AbstractThe 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. A systematic literature search of randomized controlled trials using Cochrane Library, PubMed, Embase, and Web of Science, was performed up to Jan. 7th, 2020. A 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. In conclusion, compared 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, yet at the price of increasing incidence of chemotherapy-induced toxicities that is well tolerated and clinically manageable.

scholarly journals Comparison of EGFR-TKI and chemotherapy in the first-line treatment of advanced EGFR mutation-positive NSCLC

Neoplasma ◽  
2013 ◽  
Vol 60 (04) ◽  
pp. 425-431 ◽  
Author(s):  
O. Fiala ◽  
M. Pesek ◽  
J. Finek ◽  
L. Benesova ◽  
Z. Bortlicek ◽  
...  
Keyword(s):  
Egfr Mutation ◽  
Line Treatment ◽  
First Line ◽  
Egfr Tki ◽  
First Line Treatment

Cost-Effectiveness of an Individualized First-Line Treatment Strategy Offering Erlotinib Based on EGFR Mutation Testing in Advanced Lung Adenocarcinoma Patients in Germany

2015 ◽  
Vol 33 (11) ◽  
pp. 1215-1228 ◽  
Author(s):  
Katharina Schremser ◽  
Wolf H. Rogowski ◽  
Sigrid Adler-Reichel ◽  
Amanda L. H. Tufman ◽  
Rudolf M. Huber ◽  
...  
Keyword(s):  
Cost Effectiveness ◽  
Lung Adenocarcinoma ◽  
Treatment Strategy ◽  
Egfr Mutation ◽  
Mutation Testing ◽  
Line Treatment ◽  
First Line ◽  
First Line Treatment ◽  
Egfr Mutation Testing

scholarly journals The Efficacy of First-Generation EGFR-TKI Combined With Brain Radiotherapy as the First-Line Treatment for Lung Adenocarcinoma Patients With Brain Metastases and EGFR Sensitive Mutations: A Retrospective study

2021 ◽  
Vol 20 ◽  
pp. 153303382199781
Author(s):  
Yuting Liu ◽  
Juanjuan Wang ◽  
Jingjing Wu ◽  
Qifan Yang ◽  
Yulan Zeng ◽  
...  
Keyword(s):  
Retrospective Study ◽  
Combination Therapy ◽  
Brain Metastases ◽  
Subgroup Analysis ◽  
First Generation ◽  
Line Treatment ◽  
First Line ◽  
Brain Radiotherapy ◽  
Egfr Tki ◽  
First Line Treatment

Background: It was controversial that whether LUAD patients with brain metastases (BMs) and EGFR sensitive mutations should be conducted using brain radiotherapy when treated with first-generation EGFR-TKI. Herein, a retrospective study was designed to compare the efficacy of first-generation EGFR-TKI combined with brain radiotherapy and EGFR-TKI alone as first-line treatment for these LUAD patients. Patients and Methods: We retrospectively analyzed the status of patients with advanced LUAD carrying EGFR sensitive mutations who received first-generation EGFR-TKI treatment in our center. iPFS was the first time of intracranial progression or death from the diagnosis of BMs, PFS was the time of progression of any site or death from the diagnosis of BMs, and OS was the time of confirmed BMs to death or the last follow-up time. Differences in characteristics between groups were compared using the Chi-square test. The Kaplan-Meier method was used to calculate the iPFS, PFS, and OS. Univariate analysis, multivariate analysis, and subgroup analysis were conducted by Cox regression model. Results: There were 77 patients (77/134, 57.5%) in the TKI + RT group and 57 patients (57/134, 42.5%) in the TKI group. TKI + RT group had a significant higher intracranial ORR and DCR, and the combination therapy was independently significantly associated with a longer iPFS (18.9 vs. 10.5 months, P = 0.0009), systematic PFS (12.5 vs. 8.4 months, P = 0.0071) and OS (30.8 vs. 22.7 months, P = 0.0183). Females, non-smokers, and younger patients benefited more from the combination therapy. Subgroup analysis demonstrated that the combination therapy could improve the iPFS in patients with more than 3 BMs ( P = 0.005); however, it couldn’t improve the OS for these patients. Conclusion: Our study confirmed the effect of the combination of EGFR-TKI and brain radiotherapy as first-line treatment for LUAD patients with BMs and EGFR sensitive mutations.

Concurrent osimertinib plus gefitinib for first-line treatment of EGFR-mutated non-small cell lung cancer (NSCLC).

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 9507-9507 ◽  
Author(s):  
Julia K Rotow ◽  
Daniel Botelho Costa ◽  
Cloud P. Paweletz ◽  
Mark M. Awad ◽  
Paul Marcoux ◽  
...  
Keyword(s):  
Combination Therapy ◽  
Egfr Mutation ◽  
Acquired Resistance ◽  
Survival Outcomes ◽  
Line Treatment ◽  
First Line ◽  
Primary Endpoints ◽  
Egfr Mutated ◽  
Egfr Tki ◽  
First Line Treatment

9507 Background: First-line treatment with an EGFR tyrosine kinase inhibitor (TKI) is standard of care for patients (pts) with EGFR-mutated NSCLC. The EGFR TKI osimertinib is active against the acquired gefitinib-resistant mutation EGFR T790M, as is gefitinib against the osimertinib-resistant EGFR C797S. Preclinical evidence suggests dual EGFR inhibition with gefitinib + osimertinib may delay emergence of acquired resistance. Methods: This ongoing phase I/II study enrolled pts with stage IV EGFR-mutated (L858R or del19) NSCLC, without prior therapy for metastatic disease. Treatment in dose escalation (n = 6): concurrent osimertinib 40 mg or 80 mg + gefitinib 250 mg daily. In dose expansion (n = 21): osimertinib + gefitinib at the maximum tolerated dose (MTD). Prior to protocol amendment 6 pts received alternating monthly cycles of TKI monotherapy and were excluded from this analysis. The primary endpoints in the dose escalation and expansion phases were, respectively, identification of the MTD and feasibility, defined as receipt of combination therapy for ≥ 6 four-week cycles. Secondary endpoints included overall response rate (ORR), survival outcomes, plasma EGFR mutation clearance (cell free DNA by droplet digital PCR (ddPCR)), and mechanisms of acquired resistance. Results: From May 2017 to July 2019 27 pts were enrolled and evaluable for the primary endpoints. The MTD was osimertinib 80 mg plus gefitinib 250 mg orally daily. In feasibility analysis, 81.5% completed ≥6 cycles combination therapy (1 pt discontinued for progression, 4 for toxicity). The ORR was 85.2% (95% CI 67.5%-94.1%). Best response: 85.2% partial response, 14.8% stable disease. The most common treatment-related adverse effects (TRAEs) (% any grade, % grade 3) were rash (96.3%, 3.7%), diarrhea (85.2%, 11.1%) and dry skin (70.4%, 0%). Plasma ddPCR (n = 25 pts) detected the driver EGFR mutation at baseline in 68% of pts. In these pts, plasma EGFR cleared to undetectable at 2 weeks treatment in 82.4%. At 14.8 months median follow up the median progression free survival was not yet reached. Conclusions: Combination therapy with osimertinib and gefitinib is tolerable for first-line treatment of EGFR-mutated NSCLC and resulted in rapid plasma clearance of the EGFR mutation. The observed ORR is consistent with previously reported first-line response rates to osimertinib. Analysis of survival outcomes and acquired resistance mechanisms are pending data maturity and will facilitate understanding of the role of first-line dual EGFR TKI therapy for this pt population. Clinical trial information: NCT03122717 .

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