Relationship between PD-L1 expression and outcome in EGFR-mutant lung cancer patients treated with EGFR tyrosine kinase inhibitors

Liu, Jia; Itchins, Malinda; Nagrial, Adnan; Cooper, Wendy A.; Silva, Madhawa De; Barnet, Megan; Varikatt, Winny; Sivasubramaniam, Vanathi; Davis, Alexander; Gill, Anthony J.; Blinman, Prunella; Lee, Kenneth; Hui, Rina; Gao, Bo; Pavlakis, Nick; Clarke, Stephen; Lee, Jenny; Boyer, Michael; Kao, Steven

doi:10.1016/j.lungcan.2021.03.004

Cited by 29 publications

(24 citation statements)

References 18 publications

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“…Preclinical studies show that EGFR-mutant NSCLC cell lines with high PD-L1 expression exhibit induced epithelial-mesenchymal transition and less susceptibility to EGFR-TKIs via activation of transforming growth factor-β/ SMAD canonical signaling (31). Moreover, previous clinical studies indicated that EGFR-mutant NSCLC patients exhibiting ≥50% tumor PD-L1 expression have a shorter PFS following treatment with the first-generation EGFR-TKI gefitinib, relative to patients showing tumor PD-L1 expression of <50%, which agreed with the findings of the present study (26)(27)(28)(29)(30). Consistent with these findings, in the present study, we found that high tumor PD-L1 expression (≥50%) was associated with poor outcomes of EGFR-TKI monotherapy in EGFR-mutant NSCLC patients.…”

Section: Discussionsupporting

confidence: 91%

“…PD-L1 expression in NSCLC cells (25). Meanwhile, tumor PD-L1 expression was identified as a negative predictor of outcome in EGFR-mutated advanced NSCLC patients treated with first-or second-generation EGFR-TKIs (26)(27)(28)(29)(30). However, the effect of tumor PD-L1 level on the efficacy of osimertinib monotherapy in EGFR-mutated advanced NSCLC patients remains unknown.…”

Section: Introductionmentioning

confidence: 99%

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Impact of tumor programmed death ligand-1 expression on osimertinib efficacy in untreated EGFR-mutated advanced non-small cell lung cancer: a prospective observational study

Yoshimura¹,

Yamada²,

Okuma³

et al. 2021

Transl Lung Cancer Res

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Background: Osimertinib monotherapy is currently the standard of care as a first-line treatment for patients harboring epidermal growth factor receptor (EGFR) mutations; however, some EGFR-mutated non-small cell lung cancer (NSCLC) patients exhibit primary resistance and an insufficient response to EGFR-tyrosine kinase inhibitors (EGFR-TKIs). Elevated programmed death-ligand 1 (PD-L1) expression in tumors was reported as a negative predictive factor for outcomes of first-or second-generation EGFR-TKIs.Methods: We prospectively assessed advanced NSCLC patients with EGFR mutations who were treated with osimertinib at 14 institutions in Japan between September 2019 and December 2020. Relationships between outcomes of osimertinib monotherapy and patients' characteristics were reviewed.Results: Seventy-one patients who underwent the tumor PD-L1 test were enrolled. Multivariate analysis identified tumor PD-L1 expression as an independent predictor for progression-free survival (PFS) with osimertinib treatment (P=0.

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Section: Discussionsupporting

confidence: 91%

Section: Introductionmentioning

confidence: 99%

Impact of tumor programmed death ligand-1 expression on osimertinib efficacy in untreated EGFR-mutated advanced non-small cell lung cancer: a prospective observational study

Yoshimura¹,

Yamada²,

Okuma³

et al. 2021

Transl Lung Cancer Res

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“…To further explore our cohort, we analysed PD-L1 expression levels. Several studies on the predictive role of PD-L1 expression and TKIs efficacy in EGFR-mutated NSCLC have shown conflicting results [ 21 , 22 , 23 , 24 ]. However, none have evaluated PD-L1 expression in relation to co-mutational profile.…”

Section: Discussionmentioning

confidence: 99%

Clinical and Molecular Features of Epidermal Growth Factor Receptor (EGFR) Mutation Positive Non-Small-Cell Lung Cancer (NSCLC) Patients Treated with Tyrosine Kinase Inhibitors (TKIs): Predictive and Prognostic Role of Co-Mutations

Bironzo

Reale

Sperone

et al. 2021

Cancers

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Background: Tyrosine kinase inhibitors (TKIs) show variable efficacy in epidermal growth factor receptor mutation-positive (EGFR+) NSCLC patients, even in patients harbouring the same mutation. Co-alterations may predict different outcomes to TKIs. Methods: We retrospectively analysed all consecutive EGFR+ advanced NSCLC treated with first-line TKIs at our Institutions. NGS with a 22 genes clinical panel was performed on diagnostic specimens. PD-L1 expression was also evaluated. Results: Of the 106 analysed specimens, 59 showed concomitant pathogenic mutations. No differences in OS (mOS 22.8 vs. 29.5 months; p = 0.088), PFS (mPFS 10.9 vs. 11.2 months; p = 0.415) and ORR (55.9% vs. 68.1%; p = 0.202) were observed comparing patients without and with co-alterations. Subgroup analysis by EGFR mutation type and TKIs generation (1st/2nd vs. 3rd) did not show any difference too. No correlations of PD-L1 expression levels by co-mutational status were found. Significant associations with presence of co-alterations and younger age (p = 0.018) and baseline lymph nodes metastases (p = 0.032) were observed. Patients without concomitant alterations had a significant higher risk of bone progression (26.5% vs. 3.3%, p = 0.011). Conclusions: Pathogenic co-alterations does not seem to predict survival nor efficacy of EGFR TKIs in previously untreated advanced NSCLC.

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“…In addition, patients showing acquired resistance not engendered by T790M mutations are likely to exhibit high PD-L1 levels 24 , 25 . High PD-L1 expression may be result from the activation of other alternative oncogenic pathway and these pateints may benefit from ICIs administration 36 . Our study confirmed that T790M remains a poor prognostic marker not only for ICIs alone but also for ICIs combined with chemotherapy.…”

Section: Discussionmentioning

confidence: 99%

Comparison of the outcome between immunotherapy alone or in combination with chemotherapy in EGFR-mutant non-small cell lung cancer

Shen

Chao

Shiao

et al. 2021

Sci Rep

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Whether ICIs combined with chemotherapy can improve outcomes in EGFR-mutant non-small cell lung cancer (NSCLC) remains uncertain. Patients with EGFR-mutant NSCLC and who progressed on first-line EGFR-TKIs treatment were retrospectively collected. We reviewed the outcome of these patients treated with ICIs or ICIs combined chemotherapy (ICI + C). Total 30 patients were included. The ORR were 9.1% and 25.0% for the ICI and ICI + C groups. The ICI + C group showed the trend of longer progression-free survival and overall survival periods. Patients without the T790M mutation had a significantly longer PFS than did those without this mutation (4.23 [95% CI: 2.75–5.72] vs. 1.70 [95% CI: 0.00–3.51] months, HR:4.45, p = 0.019). ICIs combined with chemotherapy tended to be more effective than ICIs alone in pretreated EGFR-mutant NSCLC. The T790M mutation may be a potential biomarker.

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Relationship between PD-L1 expression and outcome in EGFR-mutant lung cancer patients treated with EGFR tyrosine kinase inhibitors

Cited by 29 publications

References 18 publications

Impact of tumor programmed death ligand-1 expression on osimertinib efficacy in untreated EGFR-mutated advanced non-small cell lung cancer: a prospective observational study

Impact of tumor programmed death ligand-1 expression on osimertinib efficacy in untreated EGFR-mutated advanced non-small cell lung cancer: a prospective observational study

Clinical and Molecular Features of Epidermal Growth Factor Receptor (EGFR) Mutation Positive Non-Small-Cell Lung Cancer (NSCLC) Patients Treated with Tyrosine Kinase Inhibitors (TKIs): Predictive and Prognostic Role of Co-Mutations

Comparison of the outcome between immunotherapy alone or in combination with chemotherapy in EGFR-mutant non-small cell lung cancer

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