9144 POSTER EGFR Mutation Testing and First Line Treatment of Patients With Advanced NSCLC and Positive EGFR Mutation Status – Results From a German Registry

9569 Background: Erlotinib is indicated in first line treatment for patients with Non-Small-Cell-Lung cancer (NSCLC) harbouring EGFR mutation. Addition of anti-VEGF in combination with erlotinib in this setting is controversial. Methods: We performed a meta-analysis of randomized trials comparing VEGF inhibitor plus erlotinib with erlotinib alone in first line treatment for advanced NSCLC harbouring EGFR mutation. The outcomes included overall survival (OS), progression-free survival (PFS) objective response rate (ORR), and median duration of response (DOR). A fixed-effect model was used. Results: Four studies evaluated bevacizumab + erlotinib (ARTEMIS, NEJ026, J025667, Stinchcombe et al), and one study evaluated ramucirumab + erlotinib (RELAY). These five eligible studies included 1230 non-squamous NSCLC patients (654 with Ex19del and 568 with Leu858Arg);. Most of the patients were women (63%), Asian (85%) and non-smokers (60%), with a median age of 64 years. The combination (anti-VEGF + erlotinib) was significantly associated with improvement of PFS (hazards ratio [HR]: 0.59, 95%CI: 0.51-0.69, p < 0.00001). Improvement in PFS was seen across all subgroups analyzed. Interim analysis of OS (HR: 0.90, 95%CI; 0.68-1.19, p = 0.45) and ORR (odds ratio [OR], 1.19, 0.91-1.55, p = 0.21) were not statistically significant. DOR was statistically longer with combination (p < 0.005). Conclusions: For patients with untreated advanced NSCLC with EGFR mutation, the anti-VEGF combination with erlotinib, compared with erlotinib alone, is associated with significantly improved PFS and DOR, but mature data for OS are needed to confirm the benefit of this strategy.

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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

Frontiers in Oncology ◽

10.3389/fonc.2021.598265 ◽

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.

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LBA1_PR: Osimertinib as first-line treatment for EGFR mutation-positive advanced NSCLC: updated efficacy and safety results from two Phase I expansion cohorts

Journal of Thoracic Oncology ◽

10.1016/s1556-0864(16)30324-0 ◽

2016 ◽

Vol 11 (4) ◽

pp. S152 ◽

Cited By ~ 52

Author(s):

S. Ramalingam ◽

J.C.-H. Yang ◽

C.K. Lee ◽

T. Kurata ◽

D.-W. Kim ◽

...

Keyword(s):

Phase I ◽

Egfr Mutation ◽

Advanced Nsclc ◽

Line Treatment ◽

Efficacy And Safety ◽

First Line ◽

Two Phase ◽

First Line Treatment

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PCN63 EPIDERMAL GROWTH FACTOR RECEPTOR (EGFR) MUTATION TESTING AND FIRST LINE TREATMENT WITH GEFITINIB IS A DOMINANT STRATEGY IN THE TREATMENT OF ADVANCED NON-SMALL CELL LUNG CANCER (NSCLC)

Value in Health ◽

10.1016/j.jval.2011.02.918 ◽

2011 ◽

Vol 14 (3) ◽

pp. A166

Author(s):

G. de Lima Lopes

Keyword(s):

Egfr Mutation ◽

Growth Factor Receptor ◽

Dominant Strategy ◽

Small Cell ◽

Line Treatment ◽

Small Cell Lung ◽

First Line ◽

Epidermal Growth ◽

First Line Treatment ◽

Egfr Mutation Testing

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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

10.1101/2020.04.17.046409 ◽

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.

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Cost Effectiveness of Personalized Therapy for First-Line Treatment of Stage IV and Recurrent Incurable Adenocarcinoma of the Lung

Journal of Oncology Practice ◽

10.1200/jop.2011.000502 ◽

2012 ◽

Vol 8 (5) ◽

pp. 267-274 ◽

Cited By ~ 36

Author(s):

Elizabeth A. Handorf ◽

Sean McElligott ◽

Anil Vachani ◽

Corey J. Langer ◽

Mirar Bristol Demeter ◽

...

Keyword(s):

Cost Effectiveness ◽

Egfr Mutation ◽

Stage Iv ◽

Egfr Mutations ◽

Line Treatment ◽

First Line ◽

Adenocarcinoma Of The Lung ◽

Effectiveness Analysis ◽

First Line Treatment ◽

Egfr Mutation Testing

Cost-effectiveness analysis supports EGFR mutation testing in patients with stage IV or recurrent lung adenocarcinoma, rebiopsying if insufficient tissue is available, and first-line erlotinib treatment for those with EGFR mutations.

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Epidermal growth factor receptor (EGFR) mutation testing and first-line treatment with gefitinib as a strategy in the treatment of patients with advanced non-small cell lung cancer (NSCLC).

Journal of Clinical Oncology ◽

10.1200/jco.2011.29.15_suppl.7598 ◽

2011 ◽

Vol 29 (15_suppl) ◽

pp. 7598-7598 ◽

Cited By ~ 1

Author(s):

G. Lopes ◽

J. Segel ◽

D. S. W. Tan ◽

Y. Do ◽

T. Mok ◽

...

Keyword(s):

Lung Cancer ◽

Egfr Mutation ◽

Growth Factor Receptor ◽

Small Cell ◽

Line Treatment ◽

Small Cell Lung ◽

First Line ◽

Epidermal Growth ◽

First Line Treatment ◽

Egfr Mutation Testing

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Phase II study of gefitinib and inserted cisplatin plus docetaxel as a first-line treatment for advanced non-small cell lung cancer haboring an epidermal growth factor receptor activating mutation.

Journal of Clinical Oncology ◽

10.1200/jco.2013.31.15_suppl.8064 ◽

2013 ◽

Vol 31 (15_suppl) ◽

pp. 8064-8064 ◽

Cited By ~ 5

Author(s):

Shintaro Kanda ◽

Yuichiro Ohe ◽

Hidehito Horinouchi ◽

Yutaka Fujiwara ◽

Hiroshi Nokihara ◽

...

Keyword(s):

Egfr Mutation ◽

Advanced Nsclc ◽

Growth Factor Receptor ◽

Initial Response ◽

Line Treatment ◽

Small Cell Lung ◽

First Line ◽

Activating Mutation ◽

Epidermal Growth ◽

First Line Treatment

8064 Background: Gefitinib yields a longer progression-free survival (PFS) period than platinum–doublet chemotherapy as a first–line treatment for patients with advanced non–small–cell lung cancer (NSCLC) harboring an epidermal growth factor receptor (EGFR) activating mutation, but most patients develop resistance against gefitinib after the initial response. We hypothesized that the insertion of platinum–doublet chemotherapy during the initial response could prevent the emergence of acquired resistance and prolong survival, compared with gefitinib alone. Methods: We performed a phase ΙΙ study of the following first–line treatment for patients with advanced NSCLC with EGFR mutation. Gefitinib (250 mg) was administrated on days 1–56. After a two–week rest, three cycles of cisplatin (80 mg/m2) and docetaxel (60 mg/m2) were administered on days 71, 92, and 113. Gefitinib was re–started on day 134 and was continued until progression. The primary endpoint was the two–year PFS rate. The sample size was estimated at 33, and this treatment was considered worthy for further development if more than 11 of the 33 patients who started treatment had a 2–year PFS. Results: Thirty–three Japanese patients were enrolled. Twenty–five patients could re–start gefitinib, 12 achieved a PFS period of over 2 years, and 9 continued to receive the protocol treatment without experiencing progression. The 1–, 2–, and 3–year estimated PFS rates were 59.4%, 37.5%, and 33.8%, respectively, and the median PFS time was 19.2 months. The 1–, 2–, and 3–year estimated survival rates were 90.0%, 82.9%, and 62.4%, respectively, and the median survival time had not been reached at the time of analysis. Treatment–related deaths and unexpected severe toxicities were not seen. Conclusions: Our results indicated that first–line treatment consisting of gefitinib and inserted cisplatin plus docetaxel is promising for patients with advanced NSCLC with EGFR mutation. A phase ΙΙΙ study of this treatment compared with gefitinib alone is warranted. Clinical trial information: 000001738.

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