PD-L1 score as a prognostic biomarker in asian early-stage epidermal growth factor receptor-mutated lung cancer

Saw, Sharon; Ng, Win Pin; Zhou, Siqin; Lai, Gillianne; Tan, Aaron C.; Ang, Mei‐Kim; Lim, Darren Wan-Teck; Kanesvaran, Ravindran; Ng, Quan Sing; Jain, Amit; Tan, Wan Ling; Rajasekaran, Tanujaa; Chan, Johan; Teh, Yi Lin; Pang, Mengyuan; Yeo, Jia-Chi; Takano, Angela; Ong, Boon-Hean; Tan, Eng‐Huat; Tan, Sze Huey; Skanderup, Anders J.; Tan, Daniel

doi:10.1016/j.ejca.2022.10.012

Cited by 8 publications

(5 citation statements)

References 25 publications

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“…Furthermore, high PD-L1 expression was a harmful indicator for OS (Median OS: high 55.9 months vs. low 72.6 months) [ 75 ]. Similarly, PD-L1 ≥ 1% was correlated with worsening DFS and OS in stage I–IIIA EGFR-mutated NSCLC [ 76 ]. Regarding the prognostic effects of CD8 (cut-off values: 543 per mm 2 ) and PD-L1 (cut-off values: 1%) in resected NSCLC, CD8 positivity/PD-L1 negativity was favourable for RFS and OS [ 77 ].…”

Section: Resultsmentioning

confidence: 99%

A Review of Biomarkers and Their Clinical Impact in Resected Early-Stage Non-Small-Cell Lung Cancer

Cao,

Tang,

Zeng

et al. 2023

Cancers

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The postoperative survival of early-stage non-small-cell lung cancer (NSCLC) patients remains unsatisfactory. In this review, we examined the relevant literature to ascertain the prognostic effect of related indicators on early-stage NSCLC. The prognostic effects of the epidermal growth factor receptor (EGFR), anaplastic lymphoma kinase (ALK), mesenchymal–epithelial transition (MET), C-ros oncogene 1 (ROS1), or tumour protein p53 (TP53) alterations in resected NSCLC remains debatable. Kirsten rat sarcoma viral oncogene homologue (KRAS) alterations indicate unfavourable outcomes in early-stage NSCLC. Meanwhile, adjuvant or neoadjuvant EGFR-targeted agents can substantially improve prognosis in early-stage NSCLC with EGFR alterations. Based on the summary of current studies, resected NSCLC patients with overexpression of programmed death-ligand 1 (PD-L1) had worsening survival. Conversely, PD-L1 or PD-1 inhibitors can substantially improve patient survival. Considering blood biomarkers, perioperative peripheral venous circulating tumour cells (CTCs) and pulmonary venous CTCs predicted unfavourable prognoses and led to distant metastases. Similarly, patients with detectable perioperative circulating tumour DNA (ctDNA) also had reduced survival. Moreover, patients with perioperatively elevated carcinoembryonic antigen (CEA) in the circulation predicted significantly worse survival outcomes. In the future, we will incorporate mutated genes, immune checkpoints, and blood-based biomarkers by applying artificial intelligence (AI) to construct prognostic models that predict patient survival accurately and guide individualised treatment.

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Section: Resultsmentioning

confidence: 99%

A Review of Biomarkers and Their Clinical Impact in Resected Early-Stage Non-Small-Cell Lung Cancer

Cao,

Tang,

Zeng

et al. 2023

Cancers

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“…Thus, the prognostic value of PD-1/PD-L1 pathway in Filipino cohort treated with TKIs is largely unknown to this date. However, previous clinical findings seem to suggest that the PD-1/PD-L1 pathway could render insufficient in describing the real contribution of immune checkpoint pathways in the treatment outcomes due to a significantly lower PD-L1 expression in Asian cohort with EGFR-mutant NSCLC than in wildtype ( 66 ). Indeed, PD-L1 negative NSCLC tend to be more prevalent than those with low and high PD-L1 expression in Filipino cohort ( 67 ).…”

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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“…Although in our study, the ORR was not associated with PD-L1 expression, the DCR had a downward trajectory as PD-L1 expression increased. Studies regarding the prognostic or predictive value of PD-L1 expression in NSCLC can be divided into different types according to the scope of the target population, including those focusing on the whole NSCLC population, [16][17][18] or EGFRm population, [19][20][21][22] or EGFRm population treated with EGFR-TKIs [12][13][14][15][23][24][25][26][27][28][29][30][31][32][33][34] as in the current study. In addition, there have also been studies which have investigated the value of PD-L1 expression on mRNA level.…”

Section: Discussionmentioning

confidence: 99%

“…Studies regarding the prognostic or predictive value of PD‐L1 expression in NSCLC can be divided into different types according to the scope of the target population, including those focusing on the whole NSCLC population, 16 , 17 , 18 or EGFRm population, 19 , 20 , 21 , 22 or EGFRm population treated with EGFR ‐TKIs 12 , 13 , 14 , 15 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 as in the current study. In addition, there have also been studies which have investigated the value of PD‐L1 expression on mRNA level.…”

Section: Discussionmentioning

confidence: 99%

Influence of PD‐L1 expression on the efficacy of EGFR‐TKIs in EGFR‐mutant non‐small cell lung cancer

Lei

et al. 2023

Thoracic Cancer

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BackgroundEvidence on the influence of programmed death‐ligand 1 (PD‐L1) expression on the efficacy of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR‐TKIs) in EGFR‐mutant non‐small cell lung cancer (NSCLC) patients is at variance.MethodsA single‐center retrospective study was conducted to evaluate the influence of PD‐L1 expression on the efficacy of EGFR‐TKIs for NSCLC patients with EGFR mutation. Clinical information was retrieved from electronic medical records. The patients were divided into three subgroups according to PD‐L1 expression level: PD‐L1 < 1% (negative), PD‐L1 1%–49% and PD‐L1 ≥ 50%. The clinicopathological features, overall response rate (ORR), progression‐free survival (PFS) and comutation information were collected and compared between the three subgroups.ResultsA total of 117 patients were included. For PD‐L1 < 1%, PD‐L1 1%–49% and PD‐L1 ≥ 50% group, there were 39 (33.3%), 51 (43.5%) and 27 (23.0%) patients respectively, and the ORR was 43.2%, 64.0%, and 51.9%, respectively (p = 0.162), and the median progression‐free survival (mPFS) was 22.0 months (95% CI: 14.0–29.9 months), 15.4 months (95% CI: 8.9–21.8 months) and 13.0 months (95% CI: 10.6–15.3 months), respectively (log‐rank, p = 0.01). The mPFS was negatively correlated with PD‐L1 expression level (r = −0.264, p = 0.041) and PD‐L1 expression was an independent risk factor for worse PFS of EGFR‐TKIs in multivariate Cox regression. Patients with concurrent TP53 mutation had shorter PFS (p = 0.039) and the patients harboring both mutant TP53 and positive PD‐L1 had the shortest PFS (p = 0.006).ConclusionsThe efficacy of EGFR‐TKIs was influenced by the baseline PD‐L1 expression. Higher PD‐L1 expression was associated with shorter PFS. The combined indicators of TP53 and PD‐L1 identified subgroups showing divergent benefits from EGFR‐TKIs.

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PD-L1 score as a prognostic biomarker in asian early-stage epidermal growth factor receptor-mutated lung cancer

Cited by 8 publications

References 25 publications

A Review of Biomarkers and Their Clinical Impact in Resected Early-Stage Non-Small-Cell Lung Cancer

A Review of Biomarkers and Their Clinical Impact in Resected Early-Stage Non-Small-Cell Lung Cancer

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

Influence of PD‐L1 expression on the efficacy of EGFR‐TKIs in EGFR‐mutant non‐small cell lung cancer

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