The efficacy of immune checkpoint inhibitors in advanced EGFR-Mutated non-small cell lung cancer after resistance to EGFR-TKIs: Real-World evidence from a multicenter retrospective study

Hu, Jia; Huang, Di; Wang, Yanrong; Li, Donghui; Yang, Xiaojing; Yan, Fei; Du, Nan; Zhao, Yan; Li, Xiaosong; Ma, Junxun; Hu, Yi

doi:10.3389/fimmu.2022.975246

Cited by 6 publications

(3 citation statements)

References 37 publications

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“…There are 23 clinical trials and 37 retrospective studies in patients with EGFR -mutant-positive NSCLC based on immunotherapy, and most data of them are from subgroups ( Tables 1 and 2 ) 9 , 11 , 17 – 74 . When pooling activity data in the meta-analysis indeed, the pooled ORR of EGFR -mutant patients treated with immunotherapy in clinical trials was 6% (95% CI: 3–9, I ² = 0%), while 8% (95% CI: 6–11, I ² = 43%) in retrospective studies ( Figure 2 ).…”

Section: Resultsmentioning

confidence: 99%

Efficacy of immunotherapy in patients with oncogene-driven non-small-cell lung cancer: a systematic review and meta-analysis

Chen,

Lu,

Chen

et al. 2024

Ther Adv Med Oncol

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Background: Immunotherapy is an emerging antitumor therapy that can improve the survival of patients with advanced non-small-cell lung cancer (NSCLC). However, only about 20% of NSCLC patients can benefit from this treatment. At present, whether patients with driving gene-positive NSCLC can benefit from immunotherapy is one of the hot issues. Therefore, we conducted a meta-analysis to evaluate the efficacy of immunotherapy in patients with oncogene-driven NSCLC and concluded the efficacy of altered subtypes. Methods: A literature search was performed using PubMed, Web of Science, and Cochrane databases. The primary endpoints included the objective response rate (ORR), median progression-free survival (mPFS), and median overall survival (mOS) in patients with oncogene-driven NSCLC. Results: In all, 86 studies involving 4524 patients with oncogene-driven NSCLC were included in this meta-analysis. The pooled ORRs in clinical trials treated with monoimmunotherapy of EGFR, ALK, and KRAS alteration were 6%, 0%, and 23%, respectively. In retrospective studies, the pooled ORRs of EGFR, ALK, KRAS, BRAF, MET, HER2, RET, and ROS1 alteration were 8%, 3%, 28%, 24%, 23%, 14%, 7%, and 8%, respectively. Among them, the pooled ORRs of KRAS non-G12C mutation, KRAS G12C mutation, BRAF V600E mutation, BRAF non-V600E mutation, MET-exon 14 skipping, and MET-amplification were 33% 40%, 20%, 34%, 17%, and 60%, respectively. In addition, the pooled mPFS rates of EGFR, KRAS, MET, HER2, and RET alteration were 2.77, 3.24, 2.48, 2.31, and 2.68 months, while the pooled mOS rates of EGFR and KRAS alteration were 9.98 and 12.29 months, respectively. In prospective data concerning EGFR mutation, the pooled ORR and mPFS treated with chemo-immunotherapy (IC) reached 38% and 6.20 months, while 58% and 8.48 months with chemo-immunotherapy plus anti-angiogenesis therapy (ICA). Moreover, the pooled mPFS and mOS of monoimmunotherapy was 2.33 months and 12.43 months. Conclusions: EGFR-, ALK-, HER2-, RET-, and ROS1-altered NSCLC patients have poor reactivity to monoimmunotherapy but the efficacy of immune-based combined therapy is significantly improved. KRAS G12C mutation, BRAF non-V600E mutation, and MET amplification have better responses to immunotherapy, and more prospective studies are needed for further research.

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Section: Resultsmentioning

confidence: 99%

Efficacy of immunotherapy in patients with oncogene-driven non-small-cell lung cancer: a systematic review and meta-analysis

Chen,

Lu,

Chen

et al. 2024

Ther Adv Med Oncol

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“…In recent years, more and more real-world studies have found that some EGFR-TKI-resistant NSCLC patients could indeed benefit from PD-1/PD-L1 antibody combined with chemotherapy, although anti-PD-1/PD-L1 monotherapy is demonstrated to be poor effective. For example, Hu et al [ 31 ] found in 99 NSCLC patients with EGFR-TKI resistance that immunochemotherapy was significantly more effective than ICI monotherapy (median PFS: 5.0 vs. 3.0 months, P = 0.02; median OS: 19.0 vs. 7.4 months, P = 0.009). Sun et al [ 32 ] (median PFS: 5.9 vs. 2.4 months, P = 0.001) and Tian et al [ 33 ] both reported similar results (median PFS: 5.5 vs. 2.2 months, P = 0.002; median OS: 14.4 vs. 7.0 months, P = 0.001).…”

Section: Discussionmentioning

confidence: 99%

Full spectrum flow cytometry-powered comprehensive analysis of PBMC as biomarkers for immunotherapy in NSCLC with EGFR-TKI resistance

Zhou¹,

Chu²,

Zhao³

et al. 2023

Biol Proced Online

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Background Clinical studies suggest that immune checkpoint inhibitor (ICI) monotherapy has limited benefits in non-small cell lung cancer (NSCLC) patients after epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) failure. However, data about efficacy of ICI plus chemotherapy remain controversial, probably attributed to the heterogeneity among such population, and robust efficacy biomarkers are urgent to explore. Methods A total of 60 eligible patients who received ICI plus chemotherapy after EGFR-TKI treatment failure were enrolled, 24 of whom peripheral blood mononuclear cell (PBMC) samples were collected at baseline and after 2 cycles of treatment. We have designed a 23-color-antibody panel to detect PBMC by full spectrum flow cytometry. Results For EGFR-TKI resistant NSCLC patients: 1) ICI plus chemotherapy achieved an objective response rate (ORR) of 21.7% and a median progression-free survival (PFS) of 6.4 months. 2) clinical characteristics associated with worse efficacy included liver metastasis and platelet-to-lymphocyte ratio (PLR) > 200. 3) the proportion of immune cell subset associated with better efficacy was higher baseline effective CD4+T cells (E4). 4) the baseline expression of immune checkpoint proteins (ICPs) on cell subsets associated with better efficacy included: higher expression of CD25 on dendritic cells (DC) and central memory CD8+T cells (CM8), and higher expression of Lymphocyte activation gene 3 (LAG-3) on effective memory CD8+T cells (EM8). 5) the expression of ICPs after 2 cycles of treatment associated with better efficacy included: higher expression of CD25 on CD8+T/EM8 /natural killer (NK) cells. 6) the dynamic changes of ICPs expression associated with worse efficacy included: significantly decrease of T cell immunoglobulin and ITIM domain (TIGIT) expression on regular T cells (Tregs) and decrease of V-domain immunoglobulin suppressor of T cell activation (VISTA) expression on Th1. 7) a prediction model for the efficacy of ICI plus chemotherapy was successfully constructed with a sensitivity of 62.5%, specificity of 100%, and area under curve (AUC) = 0.817. Conclusions Some EGFR-TKI-resistant NSCLC patients could indeed benefit from ICI plus chemotherapy, but most patients are primary resistant to immunotherapy. Comprehensive analysis of peripheral immune cells using full spectrum flow cytometry showed that compared to the proportion of cell subsets, the expression type and level of ICPs on immune cells, especially CD25, were significantly correlated with the efficacy of immunotherapy.

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“…For example, anaplastic lymphoma kinase (ALK) and epidermal growth factor receptor (EGFR) mutations are associated with decreased response rates to ICIs and lower TMB scores. Therefore, for those patients, treatment with ICIs is not recommended as first-line therapy but may be considered after the failure of tyrosine kinase inhibitors [ 108 , 109 ]. However, in KRAS-mutated NSCLC, the percentage of TMB and expression of PD-L1 seems to depend on the KRAS polymorphism, and its clinical role requires further investigation [ 110 ].…”

Section: Advances In Predictive Biomarkersmentioning

confidence: 99%

Refining PD-1/PD-L1 assessment for biomarker-guided immunotherapy - a review

Zdrenka,

Kowalewski,

Ahmadi

et al. 2023

Biomol Biomed

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Anti-programmed cell death ligand 1 (Anti-PD-L1) immunotherapy is an increasingly crucial in cancer treatment. To date, the Federal Drug Administration has approved four PD-L1 immunohistochemistry (IHC) staining protocols, commercially available in the form of "kits", facilitating testing for PD-L1 expression. These kits comprise four PD-L1 antibodies on two separate IHC platforms, each utilizing distinct, non-interchangeable scoring systems. Several factors, including tumor heterogeneity and the size of the tissue specimens assessed, can lead to PD-L1 status misclassification, potentially hindering the initiation of therapy. Therefore, the development of more accurate predictive biomarkers to distinguish between responders and non-responders prior to anti-PD-1/PD-L1 therapy warrants further research. Achieving this goal necessitates refining sampling criteria, enhancing current methods of PD-L1 detection, and deepening our understanding of the impact of additional biomarkers. In this article, we review potential solutions to improve the predictive accuracy of PD-L1 assessment in order to more precisely anticipate patients' responses to anti-PD-1/PD-L1 therapy, monitor disease progression and predict clinical outcomes.

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The efficacy of immune checkpoint inhibitors in advanced EGFR-Mutated non-small cell lung cancer after resistance to EGFR-TKIs: Real-World evidence from a multicenter retrospective study

Cited by 6 publications

References 37 publications

Efficacy of immunotherapy in patients with oncogene-driven non-small-cell lung cancer: a systematic review and meta-analysis

Efficacy of immunotherapy in patients with oncogene-driven non-small-cell lung cancer: a systematic review and meta-analysis

Full spectrum flow cytometry-powered comprehensive analysis of PBMC as biomarkers for immunotherapy in NSCLC with EGFR-TKI resistance

Refining PD-1/PD-L1 assessment for biomarker-guided immunotherapy - a review

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