Chemotherapy Should Be Combined With Checkpoint Inhibitors in the Treatment of Patients With Stage IV EGFR-Mutant NSCLC Whose Disease Has Progressed on All Available Tyrosine Kinase Inhibitors

Zhou, Fei

doi:10.1016/j.jtho.2021.07.011

Cited by 4 publications

(5 citation statements)

References 37 publications

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“…Previous studies have shown that patients with advanced NSCLC carrying EGFR mutations have a poor response to immunotherapy, and a possible mechanism for this poor response is the low expression of PD-L1 or the lack of infiltrating T cells in the tumor microenvironment (TME) (11)(12)(13)(14). The TME generalization may change with the progression of the tumor, and therefore, resistance to EGFR-TKI may enhance the response to immunotherapy response (7,15,16).…”

Section: Discussionmentioning

confidence: 99%

Efficacy of ICI-based treatment in advanced NSCLC patients with PD-L1≥50% who developed EGFR-TKI resistance

Li,

Jiang,

Qian

et al. 2023

Front. Immunol.

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IntroductionPlatinum-based chemotherapy is still the standard of care for Epidermal growth factor receptor (EGFR) mutated non-small cell lung cancer (NSCLC) patients after developing EGFR-TKI resistance. However, no study focusing on the role of immuno checkpoint inhibitor (ICI) based treatments for EGFR mutated NSCLC patients who carried programmed death ligand 1 (PD-L1) tumor proportion score (TPS) greater than 50% progressed after EGFR-TKI therapy. In this study, we retrospectively investigated the outcomes of ICI-based treatments for EGFR mutated NSCLC patients carried PD-L1 TPS≥50% after developing EGFR-TKI resistance and to explore the population that may benefited from ICI-based treatment.MethodsWe retrospectively collected data of advanced NSCLC patients with EGFR mutations and PD-L1 TPS≥50% who have failed prior EGFR-TKI therapies without T790M mutation at Shanghai Chest Hospital between January 2018 and June 2021. Progression-free survival (PFS) and overall survival (OS) were utilized to evaluate the outcomes of this study.ResultsA total of 146 patients were included. Up to June 20th, 2022, median follow-up was 36.7 months (IQR, 12.5-44.2 months). Among the population, 66 patients (45.2%) received chemotherapy, the remaning (54.8%) received ICI-based treatment, including 56 patients(70.0%) received ICI combined with chemotherapy (IC) and 24 patients (30.0%) received ICI monotherapy (IM). In IC group,31 patients received ICI combined with chemotherapy,19 patients received ICI combined with antiangiogenic therapy and remaing received ICI combined with chemotherapy and antiangiogenic therapy. Survival analysis shown that patients who received ICI-based treatment had better progress-free survival (PFS) and overall survival (OS) compared with those treated with other therapy (median PFS, 10.0 vs. 4.0 months, P<0.001; median OS, 39.5 vs. 24.2 months, P<0.001). What’s more, patients who treated with IC treatment had a superior survival time than those received IM treatment (median PFS, 10.3 vs. 7.0 months, P<0.001; median OS, 41.6 vs. 32.4 months, P<0.001). Subgroup analysis found that the PFS and OS benefit of IC was evident in all subgroups.ConclusionsFor advanced NSCLC patients with EGFR mutations and PD-L1 TPS≥50% who have failed prior EGFR-TKI therapies without T790M mutation, ICI-based treatment could provide a more favorable survival than classical chemotherapy. What’ s more, compared with ICI monotherapy, ICI combined with chemotherapy seems to be the preferred treatment.

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Section: Discussionmentioning

confidence: 99%

Efficacy of ICI-based treatment in advanced NSCLC patients with PD-L1≥50% who developed EGFR-TKI resistance

Li,

Jiang,

Qian

et al. 2023

Front. Immunol.

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“…It was reported that disease progression after EGFR TKI treatment leads to suppression of tumor-infiltrating CD8+ T cells and induction of regulatory T cells, resulting in a noninflamed TME and insensitivity to ICI monotherapy. 18 In contrast, chemotherapeutic agents have been found to enhance CD8+ T cell infiltration and deplete immunosuppressive cells. 19 , 20 Therefore, the use of chemoimmunotherapy, a combination of ICIs and cytotoxic anticancer drugs, provides an improved immunologic status in the TME and theoretically facilitates an antitumor immune response in tumors compared with that of ICI monotherapy.…”

Section: Discussionmentioning

confidence: 99%

A Real-World Analysis of Immune Checkpoint Inhibitor-Based Therapy After Osimertinib Treatment in Patients With EGFR-Mutant NSCLC

Morimoto¹,

Sawada²,

Yamada³

et al. 2022

JTO Clinical and Research Reports

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“…This phenomenon is consistent with that observed in patients with wild-type driver gene. Although the tumor microenvironment (TME) of EGFR-mutant NSCLC is immunosuppressive (28), EGFR-TKI may activate the TME by increasing dendritic cells and CD8+ cells, reducing Tregs, and inhibiting M2-like macrophages polarization at an early stage (35). EGFR-TKI could also affect the expression of PD-L1 (36) and the distribution of the CD4+, and Foxp3+ cells within the TME (37)(38)(39).…”

Section: Discussionmentioning

confidence: 99%

“…The CT 18 study ( 18 ) and other studies using a combination approach of ICI with chemotherapy have exhibited survival benefits ( 16 , 17 ), which was also observed in our study, whereas a study with camrelizumab plus apatinib achieved inferior outcome ( 19 ). Basic studies support that chemotherapy, antiangiogenic drugs, and radiotherapy exert synergistic effects with ICI via positive regulation of the immune system, changing the tumor immune microenvironment, and releasing tumor neoantigens ( 28 – 32 ). Besides the role of ICI, the optimal combination strategy is still unclear.…”

Section: Discussionmentioning

confidence: 99%

Front-Line ICI-Based Combination Therapy Post-TKI Resistance May Improve Survival in NSCLC Patients With EGFR Mutation

Tian

et al. 2021

Front. Oncol.

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BackgroundData on the use of immune checkpoint inhibitors (ICIs) in advanced non-small cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR) mutation are limited. The current study aimed to assess the efficacy of ICIs in EGFR-mutant advanced NSCLC and explore the relevant influential factors.Materials and MethodsRelevant clinical data of EGFR-mutant NSCLC patients who had received ICIs were collected from multiple hospitals. The primary endpoint was progression-free survival (PFS), and the secondary endpoints were overall survival (OS), objective response rate (ORR), and relevant influential factors.ResultsA total of 122 advanced EGFR-mutant NSCLC patients were included in the final analysis. The total cohort had an objective response rate (ORR) of 32.0%, a median progression-free survival (mPFS) of 5.0 months, and a median overall survival (mOS) of 14.4 months. Among 96 patients with common EGFR mutations (19Del, 52 patients; L858R, 44 patients), those who were administered front-line ICI exhibited better survival benefits than those who received later-line ICI after disease progression on tyrosine kinase inhibitors (TKIs) treatment (mPFS: 7.2 months vs. 3.4 months, respectively, P < 0.0001; mOS: 15.1 months vs. 8.4 months, respectively, P <0.0001). Moreover, the efficacy of ICI-based combination therapy was better than that of ICI monotherapy (mPFS: 5.0 months vs. 2.2 months, respectively, P = 0.002; mOS: 14.4 months vs. 7.0 months, respectively, P = 0.001). Multivariate analysis showed that ICI-based combination therapy and front-line ICI administration after progression on EGFR-TKI were associated with significant improvements in both PFS and OS (P < 0.05). A high PD-L1 expression (tumor proportion score, TPS≥50%) and the EGFR L858R mutation were only significantly associated with a better PFS (P <0.05). A better Eastern Cooperative Oncology Group (ECOG) status was independently associated with a favorable OS (P <0.05).ConclusionsTaken together, combination immunotherapy in front-line was associated with improvement of survival in EGFR-mutant NSCLC patients post-TKI resistance. Further prospective studies with large sample sizes are required to identify the optimal combinatorial treatment strategy.

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Chemotherapy Should Be Combined With Checkpoint Inhibitors in the Treatment of Patients With Stage IV EGFR-Mutant NSCLC Whose Disease Has Progressed on All Available Tyrosine Kinase Inhibitors

Cited by 4 publications

References 37 publications

Efficacy of ICI-based treatment in advanced NSCLC patients with PD-L1≥50% who developed EGFR-TKI resistance

Efficacy of ICI-based treatment in advanced NSCLC patients with PD-L1≥50% who developed EGFR-TKI resistance

A Real-World Analysis of Immune Checkpoint Inhibitor-Based Therapy After Osimertinib Treatment in Patients With EGFR-Mutant NSCLC

Front-Line ICI-Based Combination Therapy Post-TKI Resistance May Improve Survival in NSCLC Patients With EGFR Mutation

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