Evidence map›Paper›PMID 40396122›Full record

ArticleTherapeutic advances in medical oncology2025

Efficacy and safety of distinct regimens for individuals with advanced EGFR-mutated non-small-cell lung cancer who progressed on EGFR tyrosine-kinase inhibitors: a systematic review and network meta-analysis.

Wengang Zhang, Jian Xiong, Yujie Li, Jing Nie, Wencheng Zhao, Zhiyi Guo, Xinyue Liu, Qianqian Zhang, Xuyang Chen, Li Ye and 8 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Therapeutic advances in medical oncology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

2 citing papers in PubMed.

  1. Article
  2. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

18 authors.

Wengang ZhangDepartment of Medical Oncology, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai, China.ORCID https://orcid.org/0009-0001-2512-5593
Jian XiongDepartment of Pulmonary and Critical Care Medicine, Yueyang Central Hospital, Yueyang, China.
Yujie LiDepartment of Medical Oncology, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai, China.
Jing NieDepartment of Medical Oncology, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai, China.
Wencheng ZhaoDepartment of Medical Oncology, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai, China.
Zhiyi GuoDepartment of Thoracic Surgery, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai, China.
Xinyue LiuDepartment of Medical Oncology, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai, China.
Qianqian ZhangDepartment of Medical Oncology, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai, China.
Xuyang ChenDepartment of Medical Oncology, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai, China.
Li YeDepartment of Medical Oncology, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai, China.
Zhimin ChenDepartment of Medical Oncology, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai, China.
Hao WangDepartment of Medical Oncology, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai, China.
Kandi XuDepartment of Medical Oncology, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai, China.
Lishu ZhaoDepartment of Medical Oncology, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai, China.
Yujin LiuDepartment of Medical Oncology, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai, China.
Lihua HuangDepartment of Medical Oncology, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai, China.
Yuhang LiDepartment of Medical Oncology, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai, China.
Yayi HeDepartment of Medical Oncology, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai 200433, China.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Background: Targeted therapy with EGFR tyrosine-kinase inhibitors (TKIs) is the preferred first-line treatment for EGFR-mutated advanced non-small-cell lung cancer (NSCLC), but acquired resistance inevitably occurs in almost all responding individuals. Objectives: We aimed to comprehensively review the literature to investigate the efficacy and safety of distinct regimens in the subsequent-line setting, thereby identifying the optimal regimen for these TKI-resistant NSCLC patients. Design: A systematic review and network meta-analysis (NMA) using a Bayesian framework. Data sources and methods: The PubMed, Embase, Cochrane Library databases, and abstracts of ASCO, ESMO, and WCLC were searched from database inception to November 3, 2024, to identify eligible randomized controlled trials (RCTs) that assessed distinct regimens for individuals with advanced EGFR-mutated NSCLC who progressed on TKIs. The outcomes of progression-free survival (PFS), overall survival (OS), objective response rate (ORR), disease control rate (DCR), and grade 3 or higher adverse events (⩾3AEs) were compared and ranked in overall patients and various subgroups among eight regimens by NMA and the surface under the cumulative ranking curve, respectively. The protocol is registered with PROSPERO, CRD42024601619. Results: In total, 14 RCTs, involving 3177 participants and 8 treatment regimens (chemotherapy plus ivonescimab (programmed cell death protein 1/vascular endothelial growth factor inhibitor; chemotherapy + ivonescimab (CT + IVO)); CT + amivantamab + lazertinib (CT + AMI + LAZ), CT + immunotherapy + bevacizumab (CT + IO + BEV), CT + AMI, CT + BEV, CT + IO, CT, and IO), were included. Overall, in patients, the most pronounced PFS benefit was observed with the "CT + IVO," followed by "CT + AMI + LAZ," "CT + IO + BEV," and "CT + AMI," ranked second, third, and fourth, respectively. In terms of OS, the regimen of "CT + AMI" ranked the best, followed by "CT + IVO." However, the comparisons of OS among different regimens did not reach statistical significance, possibly due to immature data. The results for ORR and DCR were similar to those for OS, with "CT + AMI" topping the rankings, followed by "CT + AMI + LAZ." In terms of safety, the incidence of ⩾3AEs was highest in "CT + AMI + LAZ," followed by "CT + AMI." In subgroup analysis, "CT + IVO" demonstrates stable PFS benefits across clinicopathological characteristics, ranking first in most subgroups. Due to the unavailability of OS subgroup data in most RCTs, many regimens were missing in the OS subgroup analysis. Conclusion: Integrating the results of different clinical outcomes and subgroup analyses, we conclude that "CT + IVO" is the optimal treatment option with an acceptable safety profile for patients with advanced EGFR-mutated NSCLC who have progressed on TKIs. "CT + AMI + LAZ" and "CT + AMI" are alternative subsequent line options as well, with superior efficacy compared to immunotherapy-based or chemotherapy regimens, yet elevated toxicity profiles requiring vigilant management.

Indexed as

EGFRimmunotherapyivonescimabnon-small-cell lung cancer

Identifiers

PMID40396122
PMCPMC12089717

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.