Dataset Information

Clinical Value of EGFR Copy Number Gain Determined by Amplicon-Based Targeted Next Generation Sequencing in Patients with EGFR-Mutated NSCLC.

ABSTRACT:

Background

The clinical relevance of epidermal growth factor receptor (EGFR) copy number gain in patients with EGFR mutated advanced non-small cell lung cancer on first-line tyrosine kinase inhibitor treatment has not been fully elucidated.

Objective

We aimed to estimate EGFR copy number gain using amplicon-based next generation sequencing data and explored its prognostic value.

Patients and methods

Next generation sequencing data were obtained for 1566 patients with non-small cell lung cancer. EGFR copy number gain was defined based on an increase in EGFR read counts relative to internal reference amplicons and normal controls in combination with a modified z-score ≥ 3.5. Clinical follow-up data were available for 60 patients treated with first-line EGFR-tyrosine kinase inhibitors.

Results

Specificity and sensitivity of next generation sequencing-based EGFR copy number estimations were above 90%. EGFR copy number gain was observed in 27.9% of EGFR mutant cases and in 7.4% of EGFR wild-type cases. EGFR gain was not associated with progression-free survival but showed a significant effect on overall survival with an adjusted hazard ratio of 3.14 (95% confidence interval 1.46-6.78, p = 0.003). Besides EGFR copy number gain, osimertinib in second or subsequent lines of treatment and the presence of T790M at relapse revealed significant effects in a multivariate analysis with adjusted hazard ratio of 0.43 (95% confidence interval 0.20-0.91, p = 0.028) and 0.24 (95% confidence interval 0.1-0.59, p = 0.001), respectively.

Conclusions

Pre-treatment EGFR copy number gain determined by amplicon-based next generation sequencing data predicts worse overall survival in EGFR-mutated patients treated with first-line EGFR-tyrosine kinase inhibitors. T790M at relapse and subsequent treatment with osimertinib predict longer overall survival.

SUBMITTER: Wei J

PROVIDER: S-EPMC7935828 | biostudies-literature | 2021 Mar

REPOSITORIES: biostudies-literature

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Publications

Clinical Value of EGFR Copy Number Gain Determined by Amplicon-Based Targeted Next Generation Sequencing in Patients with EGFR-Mutated NSCLC.

Wei Jiacong J Meng Pei P Terpstra Miente Martijn MM van Rijk Anke A Tamminga Menno M Scherpen Frank F Ter Elst Arja A Alimohamed Mohamed Z MZ Johansson Lennart F LF Stigt Jos J Gijtenbeek Rolof P G RPG van Putten John J Hiltermann T Jeroen N TJN Groen Harry J M HJM Kok Klaas K van der Wekken Anthonie J AJ van den Berg Anke A

Targeted oncology 20210219 2

<h4>Background</h4>The clinical relevance of epidermal growth factor receptor (EGFR) copy number gain in patients with EGFR mutated advanced non-small cell lung cancer on first-line tyrosine kinase inhibitor treatment has not been fully elucidated.<h4>Objective</h4>We aimed to estimate EGFR copy number gain using amplicon-based next generation sequencing data and explored its prognostic value.<h4>Patients and methods</h4>Next generation sequencing data were obtained for 1566 patients with non-sm ...[more]

PMID: 33606136

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Project description:BackgroundThis study aimed to investigate the efficacy of immunotherapy, as monotherapy or in combination, comparing to chemotherapy with or without anti-angiogenesis for advanced non-small cell lung cancer (NSCLC) patients progressing to epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs).MethodsWe retrospectively analyzed patients with advanced NSCLC harboring EGFR mutations who received immune checkpoint inhibitors (ICI) and/or chemotherapy after EGFR-TKIs failure at Shanghai Chest Hospital between Aug 2016 and Oct 2022. According to the subsequent immunotherapy regimen, the patients were assigned to ICI monotherapy (IM), IO plus anti-angiogenesis (IA), ICI plus chemotherapy (IC), ICI plus chemotherapy plus anti-angiogenesis (ICA). Eligible patients undergoing standard chemotherapy were assigned to chemotherapy plus anti-angiogenesis (CA) and chemotherapy alone (CM). Efficacy was evaluated according to the RECIST 1.1version, and calculated the objective response rate (ORR) and disease control rate (DCR). Survival curves were plotted using the Kaplan-Meier method, and the median progression-free survival (PFS) was calculated. Differences among survival curves of the six groups were assessed using the log-rank test.ResultsA total of 237 advanced NSCLC patients with EGFR mutations were included in this study. Of the 160 patients who received immunotherapy, 57 received ICI monotherapy, 27 received ICI plus anti-angiogenesis therapy, 43 received ICI plus chemotherapy, and 33 received ICI plus anti-angiogenesis plus chemotherapy. 77 patients received standard chemotherapy, of which 30 received chemotherapy plus anti-angiogenesis and 47 received chemotherapy alone. Patients in ICA group showed significant longer PFS than IM (7.2 vs 1.9 months, P=0.011), IA (7.2 vs 4.8 months, P=0.009) and CM group (7.2 vs 4.4 months, P=0.005). There was no significant difference in PFS between the ICA and IC (7.2 vs 5.6 months, P=0.104) or CA (7.2 vs 6.7 months, P=0.959) group. Meanwhile, the ICA group showed the highest ORR and DCR (36.4% and 90.9%) compared to the other five groups. The IC group had a higher ORR than the IA and CA group (32.6% vs 7.4% vs 10.0%, respectively), but the DCR was comparable (79.1% vs 74.1% vs 76.7%, respectively). The ORR of the CM group was 6.4% and the DCR was 66.0%. IM group showed the lowest ORR and DCR (1.8% and 36.8%). Treatment-related adverse events (TRAEs) of grade 3 or worse occurred in 9 (27.3%) patients in the ICA group, 6 (20.0%) in the CA group, 7 (14.9%) in the CM group, 5 (11.6%) in the IC group, 5 (8.8%) in the IM group, and 2 (7.4%) in the IA group.ConclusionNSCLC patients with positive EGFR mutations after EGFR-TKIs failure received subsequent immunotherapy plus anti-angiogenesis and chemotherapy are likely to have more benefits in ORR, DCR and mPFS.

Project description:Background and objectiveMutations located in epidermal growth factor receptor (EGFR) tyrosine kinase domains have been described as the 'Achilles heel' of non-small cell lung cancer (NSCLC) and can be targeted by epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs). However, the clinical benefits of EGFR-TKIs are limited, and drug resistance inevitably occurs in NSCLC patients after long-term exposure to certain drugs. EGFR-TKI combination therapies, including combined targeted therapy, radiotherapy, chemotherapy, and immunotherapy, have shown promise in addressing this issue. This literature review analyzed the rationale and controversies of clinical research related to various EGFR-TKI combination therapies.MethodsThe PubMed database was searched to retrieve articles published from January 1, 2001 to April 15, 2023 using the following Medical Subject Headings (MeSH) terms: "EGFR-mutated non-small cell lung cancer" and "clinical trial". Google Scholar was also reviewed to retrieve additional articles. The search was limited to articles published in English.Key content and findingsIn this review, we summarized EGFR-TKI combination therapies, including combined targeted therapy, radiotherapy, chemotherapy, and immunotherapy, most of which have shown efficacy and safety in patients with EGFR-mutated NSCLC. A number of clinical studies with large sample sizes have analyzed the activity and toxicity of combined therapies and explored potential and well-tolerated treatment options.ConclusionsEGFR mutations have been detected in many NSCLC patients and can be targeted by EGFR-TKIs. However, drug resistance after long-term exposure remains a significant challenge for this type of treatment. Most clinical trials have shown that the combination of EGFR-TKIs and targeted therapy, chemotherapy, radiotherapy or immunotherapy is efficacious and safe in the treatment of EGFR-mutated NSCLC. It should be noted that in some instances, serious adverse events have led to the termination of trials. However, EGFR-TKI combination therapy is indeed an effective approach for the treatment of patients with EGFR-mutated NSCLC and deserves further development.

Dataset Information

Clinical Value of EGFR Copy Number Gain Determined by Amplicon-Based Targeted Next Generation Sequencing in Patients with EGFR-Mutated NSCLC.

Background

Objective

Patients and methods

Results

Conclusions

Publications

Clinical Value of EGFR Copy Number Gain Determined by Amplicon-Based Targeted Next Generation Sequencing in Patients with EGFR-Mutated NSCLC.

Similar Datasets

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