EGFR mutation status in non-small cell lung cancer receiving PD-1/PD-L1 inhibitors and its correlation with PD-L1 expression: a meta-analysis

Yang, Huimin; Zhu, Jinxiu; Xiao, Rendong; Liu, Yuhang; Yu, Fanglin; Cai, Lin; Qiu, Minglian; He, Fei

doi:10.1007/s00262-021-03030-2

Cited by 12 publications

(8 citation statements)

References 75 publications

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“…Unlike tumors with PD‐L1 expression, tumors with driver mutations are characterized by a lower tumor mutation burden and neoantigens 19 . Our study also revealed that the PD‐L1 expression level was significantly lower in tumors with EGFR common mutations, as previously reported 20 . Meanwhile, tumors with ALK rearrangement have been reported to show high expression of PD‐L1 through an intrinsic mechanism where the JAK‐STAT3 pathway, which is the downstream of ALK, promotes PD‐L1 transcription 21 .…”

Section: Discussionsupporting

confidence: 86%

“… 19 Our study also revealed that the PD‐L1 expression level was significantly lower in tumors with EGFR common mutations, as previously reported. 20 Meanwhile, tumors with ALK rearrangement have been reported to show high expression of PD‐L1 through an intrinsic mechanism where the JAK‐STAT3 pathway, which is the downstream of ALK, promotes PD‐L1 transcription. 21 In tumors with uncommon EGFR mutations, considerably high expression of PD‐L1 was observed (although it should be noted that the population was small).…”

Section: Discussionmentioning

confidence: 99%

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Significance of programmed death‐ligand 1 expression in resected lung cancer and its relationship with EGFR mutation

et al. 2023

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BackgroundSeveral studies have reported that the high expression of programmed death‐ligand 1 (PD‐L1) within tumor cells predicts a poor prognosis. However, the relationship between the PD‐L1 expression and lymph node metastasis or driver mutations in lung cancer remains poorly understood.MethodsA total of 356 consecutive patients who underwent surgical resection for primary lung cancer were included in the study. There were 268 adenocarcinomas including 100 EGFR mutations, 67 squamous cell carcinomas (Sq), and 21 other histologies. The high expression of PD‐L1 was defined as a tumor proportion score (TPS) of ≥50. The relationship between the PD‐L1 expression and clinicopathological factors and recurrence‐free survival (RFS) was analyzed.ResultsThe PD‐L1 expression was high in 75 patients. It was significantly related to smoking history, Sq histology, driver mutation negative, elevated serum carcinoembryonic antigen levels, and lymph node metastasis. Among patients with driver mutations, a high PD‐L1 TPS was found in patients with EGFR G719X mutation. A significant difference in RFS was observed in adenocarcinoma patients. A multivariate analysis of adenocarcinoma cases revealed that tumor size and lymph node metastasis were independent prognostic factors for poor RFS, while the PD‐L1 expression was not. A logistic regression analysis revealed that the absence of driver mutations, lymph node metastasis, and a history of smoking were significantly associated with the high expression of PD‐L1.ConclusionLymph node metastasis was positively related with the high expression of PD‐L1, resulting in poor RFS. A high PD‐L1 TPS was observed in patients with the EGFR G719X mutation.

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Section: Discussionsupporting

confidence: 86%

Section: Discussionmentioning

confidence: 99%

Significance of programmed death‐ligand 1 expression in resected lung cancer and its relationship with EGFR mutation

et al. 2023

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“…In this regard, one recent metanalysis included 32 studies and calculated the association between the EGFR mutant status and PD‐L1 expression. Those tumor samples harboring EGFR mutations were associated with lower PD‐L1 expression rates, thus indicating that EGFR mutants might not be good candidates for ICIs as monotherapy after progression to targeted therapy 28 . This study also reported lower rates of PD‐L1 positive and high PD‐L1 positive samples in EGFR mutant compared with EGFR wild‐type tumors.…”

Section: Discussionmentioning

confidence: 63%

Modifying factors of PD‐L1 expression on tumor cells in advanced non‐small‐cell lung cancer

et al. 2022

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Background: Programmed death ligand-1 (PD-L1) expression predicts immunotherapy utility in nononcogenic addictive lung adenocarcinoma (ADC). However, its reproducibility and reliability may be compromised outside clinical trials. This study aimed to evaluate factors associated with PD-L1 expression in lung ADC. Methods: This observational study assessed 547 tumor samples with advanced lung ADC from January 2016 to December 2020 in a single cancer institution. Tumor samples were stained by at least one approved PD-L1 clone, SP263 (Ventana) or 22C3 (Dako), and stratified in tumor proportion score (TPS) <1%, 1-49%, or ≥50%. Results: Of all the tumor samples, positive PD-L1 staining was higher in poorly differentiated tumors (67.3% vs. 32.7%, p < 0.001). Analytical factors associated with a PD-L1 high expression (TPS ≥ 50%) were the SP263 clone (19.6% vs. 8.2%, p < 0.001), time of archival tumor tissue <12 months (15.3% vs. 3.8%, p = 0.024), whenever the analysis was performed in the most recent years (2019-2020) (19.0% vs. 8.3%, p < 0.001), and whenever the analysis was performed by pathologists in the academic setting (Instituto Nacional de Cancerologia, INCan) (19.9% vs. 11.9%, p = 0.001). In the molecular analysis, EGFR wild-type tumors had an increased proportion of PD-L1 positive and PD-L1 high cases (60.2% vs. 47.9%, p = 0.006 and 17.4% vs.8.5%, p = 0.004). A moderate correlation (r = 0.69) in the PD-L1 TPS% was observed between the two different settings (INCan vs. external laboratories). Conclusion: Clinicopathological factors were associated with an increased PD-L1 positivity rate. These differences were significant in the PD-L1 high group and associated with the academic setting, the SPS263 clone, time of archival tumor tissue <12 months, and a more recent period in the PD-L1 analysis.K E Y W O R D S immunotherapy, lung adenocarcinoma, non-small-cell lung cancer, PD-L1 immunohistochemistry, programmed death-ligand 1 BACKGROUND Programmed cell death-1 (PD-1) and programmed death ligand-1 (PD-L1) have become the most studied biomarkers in lung cancer. 1 Regardless of the expression site, both Alejandro Avilés-Salas and Diana Flores-Estrada contributed equally to the conception of this work.

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“…The results of a meta-analysis of Yang’s, Lee’s, and Qian’s teams all showed that compared with conventional chemotherapy, monoimmunotherapy did not prolong the survival time of EGFR -mutant NSCLC patients. 98 – 100 And meta-analysis performed by Rui’s and Lee’s teams both showed that ICI was more effective than chemotherapy in EGFR wild-type NSCLC, which may due to the low expression of PD-L1 in EGFR -mutant NSCLC. 101 , 102 Now, there was no randomized controlled trial (RCT) concerning the effect of ICI on various subtypes of EGFR mutation.…”

Section: Discussionmentioning

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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EGFR mutation status in non-small cell lung cancer receiving PD-1/PD-L1 inhibitors and its correlation with PD-L1 expression: a meta-analysis

Cited by 12 publications

References 75 publications

Significance of programmed death‐ligand 1 expression in resected lung cancer and its relationship with EGFR mutation

Significance of programmed death‐ligand 1 expression in resected lung cancer and its relationship with EGFR mutation

Modifying factors of PD‐L1 expression on tumor cells in advanced non‐small‐cell lung cancer

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

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