Clinical and molecular characteristics associated with high PD-L1 expression in EGFR-mutated lung adenocarcinoma.
<h4>Objective</h4>Recent evidence suggests that elevated levels of PD-L1 expression may be linked to early resistance to TKI and reduced survival in NSCLC with EGFR mutations. This study aimed to characterize the clinical and molecular features of EGFR-mutated lung adenocarcinomas and de...
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Public Library of Science (PLoS)
2024-01-01
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| Online Access: | https://doi.org/10.1371/journal.pone.0307161 |
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| author | Jeremy Slomka Hugo Berthou Audrey Mansuet-Lupo Hélène Blons Elizabeth Fabre Ivan Lerner Bastien Rance Marco Alifano Jeanne Chapron Gary Birsen Laure Gibault Jennifer Arrondeau Karen Leroy Marie Wislez |
| author_facet | Jeremy Slomka Hugo Berthou Audrey Mansuet-Lupo Hélène Blons Elizabeth Fabre Ivan Lerner Bastien Rance Marco Alifano Jeanne Chapron Gary Birsen Laure Gibault Jennifer Arrondeau Karen Leroy Marie Wislez |
| author_sort | Jeremy Slomka |
| collection | DOAJ |
| description | <h4>Objective</h4>Recent evidence suggests that elevated levels of PD-L1 expression may be linked to early resistance to TKI and reduced survival in NSCLC with EGFR mutations. This study aimed to characterize the clinical and molecular features of EGFR-mutated lung adenocarcinomas and determine the prognostic significance associated with high PD-L1 expression.<h4>Materials and methods</h4>We conducted a retrospective chart review of 103 consecutive patients with advanced EGFR-mutated NSCLC, who received treatment between 01/01/2016 and 30/12/2020, at our institution.<h4>Results</h4>Among the tumors, 17% (n = 18) exhibited high PD-L1 expression (≥50% tumor proportion score), which was associated with a lower prevalence of common EGFR mutations (56% vs. 82%, p = 0.03) and a higher frequency of complex EGFR mutations (28% vs. 7%, p = 0.02). Univariate analysis did not reveal any significant differences in first-line response, progression-free survival, or overall survival between the PD-L1 ≥50% and <50% groups. However, multivariate analysis demonstrated that PD-L1 ≥50% was independently associated with shorter survival (HR = 2.57; 95%CI[1.20-5.55]; p = 0.02), along with male gender (HR = 2.77; 95%CI[1.54-4.19]; p<0.005), presence of liver metastases (HR = 5.80; 95%CI[2.86-11.75]; p<0.005) or brain metastases (HR = 1.99; 95%CI[1.13-3.52]; p = 0.02), and poor general condition at diagnosis (ECOG 3 and 4) (HR = 10.69; 95% CI[4.42-25.85]; p<0.005). Additionally, a trend towards a higher frequency of de novo resistance was observed in the PD-L1 >50% group (7% vs. 17%, p = 0.19).<h4>Conclusion</h4>High PD-L1 expression was more commonly found in lung adenocarcinomas with uncommon and complex EGFR mutations. Furthermore, high PD-L1 expression independently predicted poor survival. These findings warrant validation through prospective studies. |
| format | Article |
| id | doaj-art-ab6f3588f8cc47caa87e83f6b1a1c71b |
| institution | DOAJ |
| issn | 1932-6203 |
| language | English |
| publishDate | 2024-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj-art-ab6f3588f8cc47caa87e83f6b1a1c71b2025-08-20T02:59:46ZengPublic Library of Science (PLoS)PLoS ONE1932-62032024-01-011911e030716110.1371/journal.pone.0307161Clinical and molecular characteristics associated with high PD-L1 expression in EGFR-mutated lung adenocarcinoma.Jeremy SlomkaHugo BerthouAudrey Mansuet-LupoHélène BlonsElizabeth FabreIvan LernerBastien RanceMarco AlifanoJeanne ChapronGary BirsenLaure GibaultJennifer ArrondeauKaren LeroyMarie Wislez<h4>Objective</h4>Recent evidence suggests that elevated levels of PD-L1 expression may be linked to early resistance to TKI and reduced survival in NSCLC with EGFR mutations. This study aimed to characterize the clinical and molecular features of EGFR-mutated lung adenocarcinomas and determine the prognostic significance associated with high PD-L1 expression.<h4>Materials and methods</h4>We conducted a retrospective chart review of 103 consecutive patients with advanced EGFR-mutated NSCLC, who received treatment between 01/01/2016 and 30/12/2020, at our institution.<h4>Results</h4>Among the tumors, 17% (n = 18) exhibited high PD-L1 expression (≥50% tumor proportion score), which was associated with a lower prevalence of common EGFR mutations (56% vs. 82%, p = 0.03) and a higher frequency of complex EGFR mutations (28% vs. 7%, p = 0.02). Univariate analysis did not reveal any significant differences in first-line response, progression-free survival, or overall survival between the PD-L1 ≥50% and <50% groups. However, multivariate analysis demonstrated that PD-L1 ≥50% was independently associated with shorter survival (HR = 2.57; 95%CI[1.20-5.55]; p = 0.02), along with male gender (HR = 2.77; 95%CI[1.54-4.19]; p<0.005), presence of liver metastases (HR = 5.80; 95%CI[2.86-11.75]; p<0.005) or brain metastases (HR = 1.99; 95%CI[1.13-3.52]; p = 0.02), and poor general condition at diagnosis (ECOG 3 and 4) (HR = 10.69; 95% CI[4.42-25.85]; p<0.005). Additionally, a trend towards a higher frequency of de novo resistance was observed in the PD-L1 >50% group (7% vs. 17%, p = 0.19).<h4>Conclusion</h4>High PD-L1 expression was more commonly found in lung adenocarcinomas with uncommon and complex EGFR mutations. Furthermore, high PD-L1 expression independently predicted poor survival. These findings warrant validation through prospective studies.https://doi.org/10.1371/journal.pone.0307161 |
| spellingShingle | Jeremy Slomka Hugo Berthou Audrey Mansuet-Lupo Hélène Blons Elizabeth Fabre Ivan Lerner Bastien Rance Marco Alifano Jeanne Chapron Gary Birsen Laure Gibault Jennifer Arrondeau Karen Leroy Marie Wislez Clinical and molecular characteristics associated with high PD-L1 expression in EGFR-mutated lung adenocarcinoma. PLoS ONE |
| title | Clinical and molecular characteristics associated with high PD-L1 expression in EGFR-mutated lung adenocarcinoma. |
| title_full | Clinical and molecular characteristics associated with high PD-L1 expression in EGFR-mutated lung adenocarcinoma. |
| title_fullStr | Clinical and molecular characteristics associated with high PD-L1 expression in EGFR-mutated lung adenocarcinoma. |
| title_full_unstemmed | Clinical and molecular characteristics associated with high PD-L1 expression in EGFR-mutated lung adenocarcinoma. |
| title_short | Clinical and molecular characteristics associated with high PD-L1 expression in EGFR-mutated lung adenocarcinoma. |
| title_sort | clinical and molecular characteristics associated with high pd l1 expression in egfr mutated lung adenocarcinoma |
| url | https://doi.org/10.1371/journal.pone.0307161 |
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