Efficacy and safety of immune checkpoint inhibitors for individuals with advanced EGFR-mutated non-small-cell lung cancer who progressed on EGFR tyrosine-kinase inhibitors: a systematic review, meta-analysis, and network meta-analysis - 01/10/24

Doi : 10.1016/S1470-2045(24)00379-6

Yi Zhao, MD ^a,^{*
Co-first authors, contributed equally}, Ying He, MD ^a,^b,^{*
Co-first authors, contributed equally}, Wei Wang, MD ^a,^{*
Co-first authors, contributed equally}, Qi Cai, MD ^a,^{*
Co-first authors, contributed equally}, Fan Ge, MD ^c,^{*
Co-first authors, contributed equally}, Zisheng Chen, MD ^d,^{*
Co-first authors, contributed equally}, Jianqi Zheng, MD ^a, Yuan Zhang, MD ^a, Hongsheng Deng, MD ^a, Ying Chen, BSN ^a, Shen Lao, MD ^a, Hengrui Liang, MD ^a, Wenhua Liang, ProfMD ^a,^{^{†
Co-leading authors, contributed equally}}, Jianxing He, ProfMD ^a,^{^{†
Co-leading authors, contributed equally},}⁎

^a Department of Thoracic Surgery and Oncology, The First Affiliated Hospital of Guangzhou Medical University, State Key Laboratory of Respiratory Disease, National Clinical Research Centre for Respiratory Disease, Guangzhou, China

^b Department of Dermatology, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China

^c Department of Thoracic Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China

^d Department of Respiratory and Critical Care Medicine, The Affiliated Qingyuan Hospital (Qingyuan People’s Hospital), Guangzhou Medical University, Qingyuan, China

^* Correspondence to: Prof Jianxing He, Department of Thoracic Surgery and Oncology, The First Affiliated Hospital of Guangzhou Medical University, State Key Laboratory of Respiratory Disease, National Clinical Research Centre for Respiratory Disease, Guangzhou 510120, China Department of Thoracic Surgery and Oncology The First Affiliated Hospital of Guangzhou Medical University State Key Laboratory of Respiratory Disease National Clinical Research Centre for Respiratory Disease Guangzhou 510120 China

Summary

Background

The clinical benefits of immune checkpoint inhibitor (ICI)-based treatments in treating individuals with advanced EGFR-mutated non-small-cell lung cancer (NSCLC) who have progressed on EGFR tyrosine-kinase inhibitors (TKIs) remain controversial. We aimed to review the literature to comprehensively investigate the individual and comparative clinical outcomes of various ICI-based treatment strategies in this population.

Methods

In this systematic review and meta-analysis, we used single-arm, pairwise, and network meta-analytical approaches. We searched PubMed, Embase, Cochrane Library, Web of Science, ClinicalTrials.gov, and relevant international conference proceedings from database inception to Jan 31, 2024, without language restrictions, to identify eligible clinical trials that assessed ICI-based treatments for individuals with advanced EGFR-mutated NSCLC who progressed on EGFR-TKIs. Studies considered eligible were published and unpublished phase 1, 2, or 3 clinical trials enrolling participants with histologically or cytologically confirmed advanced EGFR-mutated NSCLC who had progressed after at least one EGFR-TKI treatment, and that evaluated ICI-based treatment strategies on at least one of the clinical outcomes of interest. The primary outcome analysed was progression-free survival. The protocol is registered with PROSPERO, CRD42021292626.

Findings

17 single-arm trials and 15 randomised controlled trials, involving 2886 participants and seven ICI-based treatment strategies (ICI monotherapy, ICI plus chemotherapy [ICI-chemo], ICI plus antiangiogenesis [ICI-antiangio], ICI plus antiangiogenesis plus chemotherapy [ICI-antiangio-chemo], dual ICIs [ICI-ICI], dual ICIs plus chemotherapy [ICI-ICI-chemo], and ICI plus EGFR-TKI [ICI-TKI]), were included. Three of these strategies—ICI monotherapy, ICI-antiangio-chemo, and ICI-chemo—had sufficient data across the included studies to perform a pairwise meta-analysis. The pairwise meta-analysis showed that, compared with chemotherapy, ICI monotherapy led to shorter progression-free survival (hazard ratio [HR] 1·73 [95% CI 1·30−2·29], I²=0%), whereas ICI-antiangio-chemo (HR 0·54 [0·44−0·67], I²=0%) and ICI-chemo (HR 0·77 [0·67−0·88], I²=0%) prolonged progression-free survival. The network meta-analysis showed that ICI-antiangio-chemo yielded the best progression-free survival results, with substantial benefits over ICI-chemo (HR 0·71 [95% credible interval 0·59−0·85]), ICI monotherapy (HR 0·30 [0·22−0·41]), and non-ICI treatment strategies including antiangio-chemo (HR 0·76 [0·58−1·00]) and chemotherapy alone (HR 0·54 [0·45−0·64]). ICI-antiangio-chemo was associated with higher risks of both any-grade and grade 3 or worse adverse events over ICI-chemo and chemotherapy in the network meta-analysis.

Interpretation

For individuals with advanced EGFR-mutated NSCLC who progressed on EGFR-TKIs, ICI-antiangio-chemo was identified as the optimal treatment option. The toxicity of this treatment was acceptable but needs careful attention. ICI-chemo showed appreciably greater efficacy than the standard-of-care chemotherapy. These findings clarified the roles of ICI-based treatment strategies in this difficult-to-treat refractory population, potentially complementing recent guidelines.

Funding

None.

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Vol 25 - N° 10

P. 1347-1356 - octobre 2024 Retour au numéro

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Efficacy and safety of immune checkpoint inhibitors for individuals with advanced EGFR-mutated non-small-cell lung cancer who progressed on EGFR tyrosine-kinase inhibitors: a systematic review, meta-analysis, and network meta-analysis - 01/10/24

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