What is the optimal first-line regimen for advanced non-small cell lung cancer patients with epidermal growth factor
Wengang Zhang1, Xinyu Zhang2, Wencheng Zhao1
1Department of Medical Oncology, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai, 200433, China.
Objectives:
There are currently various tyrosine kinase inhibitor (TKI)-based regimens available, and it can be challenging for clinicians to determine the most effective and safe option due to the lack of direct comparisons between these regimens. In this study, we conducted a network meta-analysis comparing the efficacy and safety of distinct regimens to determine the optimal regimen for patients with EGFR-mutated non-small cell lung cancer, thereby facilitating clinical decision-making.
Materials And Methods:
The PubMed, Embase, Cochrane Library databases and international conference databases were comprehensively searched from their inception to 02 April 2024 for collecting data regarding efficacy and safety from eligible randomized controlled trials (RCTs). Following literature screening and data extraction, a NMA was conducted to compare the efficacy and safety among 21 regimens with a random-effects consistency model in a Bayesian framework using a Markov Chain Monte Carlo simulation technique within the GEMTC package.
Results:
A total of 35 RCTs were included, involving 9718 individuals and 21 regimens. Compared with other interventions, combination therapies based on third-generation TKIs, especially osimertinib plus ramucirumab, showed the most favorable PFS prolongation in overall patients. Consistently, subgroup analyses showed that third-generation TKIs-based combination regimens were superior to other regimens in most prespecified subgroups with distinct clinicopathological characteristics. In terms of overall survival, despite the combination regimens based on third-generation TKIs also showing relatively superior outcomes, erlotinib plus chemotherapy and gefitinib plus chemotherapy were ranked more favorably. In terms of safety profile, combination therapies based on third-generation TKIs did not significantly increase the incidence of grade 3 or higher adverse events compared with other regimens.
Conclusion:
Our study concluded that combination regimens based on third-generation TKIs (osimertinib plus ramucirumab, osimertinib plus chemotherapy, osimertinib plus bevacizumab, amivantamab plus lazertinib and aumolertinib plus apatinib) could be the new and clinically preferable first-line, standard of care for EGFR-mutated advanced non-small cell lung cancer.
Trial Registration:
The protocol was registered in the Prospective Register of Systematic Reviews (PROSPERO CRD42023480596).
Insights
Third-generation tyrosine kinase inhibitor (TKI) combinations, particularly osimertinib plus ramucirumab, offer superior progression-free survival for EGFR-mutated non-small cell lung cancer. These regimens are recommended as a new standard of care.
Area of Science:
- Oncology
- Pharmacology
- Clinical Research
Background:
- Numerous tyrosine kinase inhibitor (TKI) regimens exist for EGFR-mutated non-small cell lung cancer (NSCLC).
- Direct comparisons are lacking, complicating clinical decision-making for optimal treatment selection.
- This study addresses the need for comparative efficacy and safety data.
Purpose of the Study:
- To conduct a network meta-analysis (NMA) comparing efficacy and safety of various TKIs in EGFR-mutated NSCLC.
- To identify the optimal TKI regimen for clinical practice.
- To facilitate informed clinical decision-making for first-line treatment.
Main Methods:
- A comprehensive search of PubMed, Embase, Cochrane Library, and conference databases was performed.
- Eligible randomized controlled trials (RCTs) published up to April 2, 2024, were included.
- A Bayesian network meta-analysis using a random-effects model and Markov Chain Monte Carlo simulation was conducted on 21 regimens from 35 RCTs (9718 patients).
Main Results:
- Third-generation TKI-based combination therapies, notably osimertinib plus ramucirumab, demonstrated the most significant progression-free survival (PFS) benefit.
- Subgroup analyses confirmed the superiority of third-generation TKI combinations across various patient subgroups.
- While third-generation TKI combinations showed promising overall survival, erlotinib plus chemotherapy and gefitinib plus chemotherapy were ranked higher; safety profiles were comparable regarding severe adverse events.
Conclusions:
- Combination regimens based on third-generation TKIs, including osimertinib plus ramucirumab, osimertinib plus chemotherapy, osimertinib plus bevacizumab, amivantamab plus lazertinib, and aumolertinib plus apatinib, are recommended.
- These regimens represent a new, clinically preferred standard of care for first-line treatment of advanced EGFR-mutated NSCLC.
- The findings support the use of these novel combinations for improved patient outcomes.
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