High PD-L1 expression correlates with primary resistance to EGFR-TKIs in treatment naïve advanced EGFR-mutant lung adenocarcinoma patients

Hsu, Kuo-Hsuan; Huang, Yen-Hsiang; Tseng, Jeng‐Sen; Chen, Kun‐Chieh; Ku, Wen-Hui; Su, Kang‐Yi; Chen, Jeremy J.W.; Chen, Huei‐Wen; Yu, Sung-Liang; Yang, Tsung‐Ying; Chang, Gee‐Chen

doi:10.1016/j.lungcan.2018.11.021

Cited by 76 publications

(72 citation statements)

References 30 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, the efficacy of EGFR‐TKI in SCC has been reported to be limited in EGFR mutation‐positive cases . Furthermore, some reports have shown the proportion of EGFR mutation‐positive lung cancer with high PD‐L1 expression (≥ 50%) to be approximately 10%; the efficacy of EGFR‐TKIs in such cases were inferior to that observed with lower expression of PD‐L1 . It was speculated that the efficacy of EGFR‐TKI in our case may be inferior to that mentioned in a previous report on SCLC harboring EGFR mutations.…”

Section: Discussioncontrasting

confidence: 78%

First‐line immune checkpoint therapy in metastatic squamous cell lung cancer harboring both EGFR mutation and high expression of PD‐L1: A case report

et al. 2020

View full text Add to dashboard Cite

A 90-year-old female was admitted to our hospital with a history of a dry cough. Chest computed tomography (CT) scan showed a tumor shadow, and CT-guided lung biopsy revealed squamous cell carcinoma harboring an EGFR mutation. In addition, programmed death-ligand 1 (PD-L1) was highly expressed with a tumor proportion score (TPS) of >75%. Pembrolizumab therapy in the first-line setting was not effective, and the patient died at six months from the first visit. Squamous cell lung cancers (SCLCs) with both EGFR mutation and high expression of PD-L1 are very rare.

show abstract

Section: Discussioncontrasting

confidence: 78%

First‐line immune checkpoint therapy in metastatic squamous cell lung cancer harboring both EGFR mutation and high expression of PD‐L1: A case report

et al. 2020

View full text Add to dashboard Cite

show abstract

“…The significant increase in PD-L1 expression in some patients may explain some of the better outcomes of second-line immunotherapy in patients with EGFR-TKI resistance. Notably, PD-L1 is upregulated in a subset of patients with NSCLC harboring EGFR mutations and is associated with primary resistance to EGFR-TKIs, with reported incidences ranging from 21 to 38.9% [41,[176][177][178]. As reported by Hsu and colleagues, a PD-L1 Tumor Proportion Score (TPS) ≧50% for clinical NSCLC specimens was associated with a significant risk of acquiring primary resistance to EGFR-TKIs when compared to patients with PD-L1 TPS < 50%, with an odds ratio (OR) of 16.47 (95% Cl: 2.10-129.16, P = 0.008) in a study of 66 surgically resected samples [177].…”

Section: Egfr-tkis Cause Dynamic Changes In Expression Of Pd-l1mentioning

confidence: 99%

“…Notably, PD-L1 is upregulated in a subset of patients with NSCLC harboring EGFR mutations and is associated with primary resistance to EGFR-TKIs, with reported incidences ranging from 21 to 38.9% [41,[176][177][178]. As reported by Hsu and colleagues, a PD-L1 Tumor Proportion Score (TPS) ≧50% for clinical NSCLC specimens was associated with a significant risk of acquiring primary resistance to EGFR-TKIs when compared to patients with PD-L1 TPS < 50%, with an odds ratio (OR) of 16.47 (95% Cl: 2.10-129.16, P = 0.008) in a study of 66 surgically resected samples [177]. Gainor and colleagues [41] detected the level of PD-L1 in paired tumor tissues before EGFR-TKI treatment and tissues after development of resistance to EGFR-TKIs, and the results showed marked increases in PD-L1 expression in 12 patients (21%).…”

Section: Egfr-tkis Cause Dynamic Changes In Expression Of Pd-l1mentioning

confidence: 99%

“…Third, tumor microenvironmental changes, a rather small window, may be most beneficial for combination EGFR blockade with immune-mediated anticancer approaches, which were found to only be temporary and disappeared as treatment continued [47]. Fourth, EGFR-TKIs may not be optimal for EGFR-TKI-naïve, high PD-L1 expressing, EGFR-mutated NSCLC as the first-line treatment due to a possible association between high PD-L1 expression and primary resistance to EGFR-TKIs [177,178]. Fifth, the combination of VEGF/VEGFR inhibitors with ICIs may represent a new option for patients with EGFR mutations for whom TKIs have failed.…”

Section: Future Prospectsmentioning

confidence: 99%

See 1 more Smart Citation

Role of the dynamic tumor microenvironment in controversies regarding immune checkpoint inhibitors for the treatment of non-small cell lung cancer (NSCLC) with EGFR mutations

et al. 2019

View full text Add to dashboard Cite

Immunotherapy has been incorporated into the first- and second-line treatment strategies for non-small cell lung cancer (NSCLC), profoundly ushering in a new treatment landscape. However, both adaptive signaling and oncogenic (epidermal growth factor receptor (EGFR)-driven) signaling may induce PD-L1 upregulation in NSCLC. Nevertheless, the superiority of immune checkpoint inhibitors (ICIs) in advanced EGFR-mutant NSCLC is only moderate. ICIs appear to be well tolerated, but clinical activity for some advanced EGFR-mutant NSCLC patients has only been observed in a small proportion of trials. Hence, there are still several open questions about PD-L1 axis inhibitors in patients with NSCLC whose tumors harbor EGFR mutations, such as the effect of EGFR tyrosine kinase inhibitors (TKIs) or EGFR mutations in the tumor microenvironment (TME). Finding the answers to these questions requires ongoing trials and preclinical studies to identify the mechanisms explaining this possible increased susceptibility and to identify prognostic molecular and clinical markers that may predict benefits with PD-1 axis inhibition in this specific NSCLC subpopulation. The presence of multiple mechanisms, including dynamic immune TME profiles, changes in PD-L1 expression and low tumor mutational burdens, may explain the conflicting data regarding the correlation between PD-L1 axis inhibitors and EGFR mutation status. We conducted a review of this currently controversial topic in an attempt to aid in the decision-making process.

show abstract

“…But unfortunately, target therapies are associated not only with high response rate, but also with unavoidable development of resistance and tumor recurrence. Meanwhile, it has been reported that the high expression of PD-L1 was a factor of primary EGFR-TKI resistance [5,6]. In present, some studies have shown that different EGFR subtypes responded differently to immunotherapy, some rare EGFR mutations have immunotherapy potential [7][8][9].…”

Section: Introductionmentioning

confidence: 98%

A Rare EGFR R748T Mutation in A Squamous Cell Lung Carcinoma Patient with PD-L1 High Expression and Response to Immuno-Chemo Combination Therapy

Sun

Lei

Liu

2020

Preprint

View full text Add to dashboard Cite

Background: In present, patients with stage IV or recurrent/metastatic non-small cell lung cancer (NSCLC) whose tumors harbor programmed death ligand 1 (PD-L1) expression and active Epidermal Growth Factor Receptor (EGFR) mutations should receive initial EGFR tyrosine kinase inhibitors (TKIs) based on clinical guidelines and practice. However, high PD-L1 expression correlates with primary resistance to EGFR-TKIs in treatment advanced EGFR-mutant lung cancer patients, the optimal use of ICI therapy in patients with actionable EGFR mutations remains an important field of ongoing research. Some studies also showed that patients with uncommon EGFR mutations have a good immunotherapy potential.Case prestation: Here, we report a 56-year old advanced squamous cell lung carcinoma (SCC) patient with a rare active mutation in EGFR gene (EGFR p.R748T) and PD-L1 expression who responded well to the immune-chemo combination therapy (pembrolizumab with nab-paclitaxel and nedaplatin). Conclusion: The EGFR R748T mutation is an uncommon active mutation and there is no report about immuno-chemo therapy on patient with EGFR R748T mutation and PD-L1 high expression. The result presented in this case provides a feasible therapy for some patients who harbor rare active EGFR mutations (except for G719X, L861Q, S768I, and Ex20 ins) with high PD-L1 expression.

show abstract

High PD-L1 expression correlates with primary resistance to EGFR-TKIs in treatment naïve advanced EGFR-mutant lung adenocarcinoma patients

Cited by 76 publications

References 30 publications

First‐line immune checkpoint therapy in metastatic squamous cell lung cancer harboring both EGFR mutation and high expression of PD‐L1: A case report

First‐line immune checkpoint therapy in metastatic squamous cell lung cancer harboring both EGFR mutation and high expression of PD‐L1: A case report

Role of the dynamic tumor microenvironment in controversies regarding immune checkpoint inhibitors for the treatment of non-small cell lung cancer (NSCLC) with EGFR mutations

A Rare EGFR R748T Mutation in A Squamous Cell Lung Carcinoma Patient with PD-L1 High Expression and Response to Immuno-Chemo Combination Therapy

Contact Info

Product

Resources

About