Prognostic Implication of PD-L1 Expression on Osimertinib Treatment for <i>EGFR</i>-mutated Non-small Cell Lung Cancer

Shiozawa, Toshihiro; Numata, Tomohiro; Tamura, Tomohide; Endo, Takeo; Kaburagi, Takayuki; Yamamoto, Yusuke; Kikuchi, Norihiro; Saito, Kazuhito; Inagaki, Masaharu; Kurishima, Koichi; Funayama, Yasunori; Miyazaki, Kôji; Koyama, Nobuyuki; Furukawa, Kinya; Nakamura, Hiroyuki; Kikuchi, Shinji; Ichimura, Hideo; Sato, Yukio; Sekine, Ikuo; Satoh, Hiroaki; Hizawa, Nobuyuki

doi:10.21873/anticanres.15736

Cited by 9 publications

(8 citation statements)

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“…Although a previous study demonstrated a significant difference in the PFS between the PD-L1 TPS ≥50% and PD-L1 TPS <50% groups, 17,18 our study and another previous study have shown no difference in prognostic F I G U R E 2 (A) Kaplan-Meier curves of the progression-free survival (PFS) for programmed cell death-ligand 1 tumor proportional score (PD-L1 TPS) ≥50% (high expression) group versus PD-L1 TPS <20% (low expression) group in patients with epidermal growth factor receptor (EGFR)-mutated non-small cell lung carcinoma (NSCLC). (B) Kaplan-Meier curves of the progression-free survival (PFS) for programmed cell death-ligand 1 tumor proportional score (PD-L1 TPS) ≥20% and <50% (intermediate expression) group versus PD-L1 TPS <20% (low expression) group in patients with epidermal growth factor receptor (EGFR)mutated non-small cell lung carcinoma (NSCLC).…”

Section: Discussionmentioning

confidence: 83%

“…9,15,16 Contrary to these studies, others have demonstrated that high PD-L1 expression adversely affects prognostic outcomes in patients receiving third-generation EGFR-TKIs. 17,18 Collectively, it remains controversial whether PD-L1 expression status is associated with prognostic outcomes in patients receiving EGFR-TKIs for EGFR-mutated NSCLC.…”

Section: Introductionmentioning

confidence: 99%

“…Regarding third‐generation EGFR–TKIs, some studies have demonstrated that prognostic outcomes of osimertinib are irrelevant to PD‐L1 expression status 9,15,16 . Contrary to these studies, others have demonstrated that high PD‐L1 expression adversely affects prognostic outcomes in patients receiving third‐generation EGFR–TKIs 17,18 …”

Section: Introductionmentioning

confidence: 99%

“… 9 , 15 , 16 Contrary to these studies, others have demonstrated that high PD‐L1 expression adversely affects prognostic outcomes in patients receiving third‐generation EGFR–TKIs. 17 , 18 …”

Section: Introductionmentioning

confidence: 99%

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Association of PD‐L1 tumor proportion score ≥20% with early resistance to osimertinib in patients with EGFR‐mutated NSCLC

Hamakawa,

Agemi,

Shiba

et al. 2023

Cancer Medicine

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BackgroundThe relationship between epidermal growth factor receptor tyrosine kinase inhibitor (EGFR‐TKI) resistance, including osimertinib, and programmed cell death‐ligand 1 (PD‐L1) expression status in EGFR‐mutated non‐small cell lung carcinoma (NSCLC) remains unclear.Patients and MethodsWe retrospectively analyzed 64 patients with unresectable advanced or metastatic NSCLC carrying EGFR exon 19 deletions (ex19del) or EGFR exon 21 L858R substitutions (L858R) who received osimertinib as the first‐line treatment. We compared progression‐free survival (PFS) between eligible patients with PD‐L1 tumor proportion scores (TPS) ≥20% and PD‐L1 TPS <20% using the Kaplan–Meier survival plots with a log‐rank test. Multivariate analysis was performed to examine the poor prognostic factors of PFS.ResultsThe PD‐L1 TPS ≥20% group included 22 cases (median [range] age: 70.5 [33–86] years; 10 women [45.5%]; 11 current or ex‐smokers [50%]); ECOG performance status (PS) of 0–1/2/3/4 was noted in 16/4/1/1 patients, respectively. The PD‐L1 TPS <20% group included 42 patients (median [range] age 73 [43–88] years; 29 women [69%]; 12 current or ex‐smokers [28.6%]); ECOG PS of 0–1/2/3/4 was noted in 33/6/3/0 cases, respectively. The median PFS was 9.1 and 28.1 months in the PD‐L1 TPS ≥20% and PD‐L1 TPS <20% groups, respectively (log‐rank p = 0.013). Multivariate analysis revealed that PD‐L1 TPS ≥20% was associated with PFS (hazard ratio: 2.35, 95% confidence interval: 1.09–5.08, p = 0.030).ConclusionPD‐L1 TPS ≥20% in patients with EGFR‐mutated NSCLC may be associated with early resistance to osimertinib.

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Section: Discussionmentioning

confidence: 83%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Association of PD‐L1 tumor proportion score ≥20% with early resistance to osimertinib in patients with EGFR‐mutated NSCLC

Hamakawa,

Agemi,

Shiba

et al. 2023

Cancer Medicine

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“…Previous reports showed that patients harboring different types (i.e., exon19 vs. exon21) and variations (i.e., 21L858R vs. 21L861Q) of EGFR mutations exhibited differential survival outcomes ( 24 , 35 - 37 ). Our initial results showed that PD-L1 differentially influenced the OS of patients with different EGFR-sensitizing mutation in both Filipinos and TCGA cohorts.…”

Section: Discussionmentioning

confidence: 99%

The differential prognostic implications of PD-L1 expression in the outcomes of Filipinos with EGFR-mutant NSCLC treated with tyrosine kinase inhibitors

Luna,

Imasa,

Juat

et al. 2023

Transl Lung Cancer Res

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Background The tumor immune microenvironment influences tumor evolution in non-small cell lung cancer (NSCLC). Yet, the prognostic value of programmed death-ligand 1 (PD-L1) in epidermal growth factor receptor (EGFR)-mutant NSCLC remains controversial. Additionally, prognostic studies in Filipinos with EGFR-mutant NSCLC remain unexplored to this day. Methods We prospectively studied the outcomes of EGFR-mutant NSCLC in Filipino cohort, and retrospectively verified the survival trend using The Cancer Genome Atlas (TCGA) cohort. Kaplan-Meier method and generalized linear regression were used to assess survival. Expression and DNA methylation of cluster of differentiation 274 ( CD274 , gene that codes for PD-L1) were examined from TCGA tumor profiles. Pearson’s correlation was used to correlate PD-L1 expression with outcomes associated with occurrence of EGFR mutations, tyrosine kinase inhibitor (TKI) types, and programmed cell death protein 1 (PD-1) expression. Proteome network analysis was used to examine the correlation between drug resistance and PD-L1. Results PD-L1 positivity was associated with significantly longer progression-free survival (PFS; P=0.0096) but had a significantly contrasting influence in the overall survival (OS; P=0.0011). PD-L1 positivity (in both protein and RNA) was associated with longer median OS (mOS) in exon21 L858R, whereas, negativity was associated with longer mOS in exon19 deletion (exon19del). Stratification (high, low, negative) of PD-L1 expression lacked significant prognostic value (all P>0.05). PD-L1/ CD274 expression (P<0.05) and DNA methylation (P<0.001) vary significantly among NSCLC subtypes and in different disease stages. Erlotinib treatment produced the longest median progression-free survival (mPFS; 874 days) relative to other EGFR-TKIs (137–311 days). PD-L1 lacked a significant correlation with EGFR-TKIs. Consistent with the immune-regulation activities of PD-1, higher expression leads to relatively shorter mOS. PD-1 correlated positively with PD-L1 expression and occurrence of exon21 L858R. Conclusions PD-L1 differentially influenced the outcomes of Filipinos with EGFR-mutant NSCLC. NSCLC subtypes, disease stage, and PD-1 expression may impact the collective outcomes associated with PD-L1 and EGFR-sensitizing mutations.

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Impact of PD-L1 Expression on the Overall Survival of Caucasian Patients with Advanced EGFR-Mutant NSCLC Treated with Frontline Osimertinib

Papazyan,

Denis,

Sagan

et al. 2024

Targ Oncol

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Prognostic Implication of PD-L1 Expression on Osimertinib Treatment for EGFR-mutated Non-small Cell Lung Cancer

Cited by 9 publications

References 0 publications

Association of PD‐L1 tumor proportion score ≥20% with early resistance to osimertinib in patients with EGFR‐mutated NSCLC

Association of PD‐L1 tumor proportion score ≥20% with early resistance to osimertinib in patients with EGFR‐mutated NSCLC

The differential prognostic implications of PD-L1 expression in the outcomes of Filipinos with EGFR-mutant NSCLC treated with tyrosine kinase inhibitors

Impact of PD-L1 Expression on the Overall Survival of Caucasian Patients with Advanced EGFR-Mutant NSCLC Treated with Frontline Osimertinib

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