Lung cancer : journal of the International Association for the Study of Lung Cancer
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Recent reports have indicated that the objective response rate (ORR) and progression-free survival (PFS) cannot serve as surrogates for predicting overall survival (OS) in immune checkpoint inhibitor (ICI) trials. We performed a trial-based correlative analysis to evaluate conventional endpoints as surrogates for predicting OS in ICI-treated non-small cell lung cancer (NSCLC) patients. ⋯ The OR-ORR and HR-PFS could serve as surrogate endpoints for predicting the HR-OS in randomized trials using ICIs for NSCLC, while the ORR and PFS could be useful endpoints for predicting OS in trials with patient selection based on high PD-L1 expression.
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Combination therapy with an inhibitor of indoleamine 2, 3-dioxygenase 1 (IDO1) and an agent targeting programmed cell death-1 (PD-1)/programmed cell death-ligand 1 (PD-L1) is expected to be a novel and effective treatment option for various solid tumors including non-small cell lung cancer (NSCLC). Therefore, it is important to elucidate the clinical and pathological features of tumors with IDO1/PD-L1 co-expression and the association between IDO1/PD-L1 co-expression and efficacy of combination therapy in NSCLC patients. In this study, we examined the prognostic impact of IDO1/PD-L1 co-expression and its relationship with tumor-infiltrating lymphocytes (TILs) in primary lung squamous cell carcinoma (SCC). ⋯ IDO1 expression correlated to PD-L1 expression, and co-expression of IDO1 and PD-L1 may be important targets for immunotherapy in lung SCC.
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In the KEYNOTE-024 trial, pembrolizumab demonstrated significant improvements in progression-free survival (PFS) and overall survival (OS) versus Standard-of-Care (SoC) platinum-based doublets for first-line treatment of PD-L1 -positive (≥50%) metastatic Non-Small-Cell Lung Cancer (NSCLC) patients with no EGFR mutations or ALK translocations. This study aims to assess the cost-effectiveness of pembrolizumab versus SoC platinum-based chemotherapy from the French healthcare system perspective. ⋯ Pembrolizumab appears cost-effective versus SoC chemotherapy for first-line treatment of PD-L1-positive (50%) metastatic NSCLC patients in France, assuming willingness-to-pay under 100,000€/QALY (OECD threshold in the discussion section).
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Immune-checkpoint inhibitors (ICIs) are now an established therapeutic option for advanced non-small cell lung cancer (NSCLC). It has remained unclear, however, whether cytotoxic chemotherapy affects the immune microenvironment in NSCLC wild type for EGFR and ALK. ⋯ Cytotoxic chemotherapy may change the biological characteristics of tumors including PD-L1 expression level and TMB.
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Epidermal growth factor receptor (EGFR) mutation-positive lung cancer accounts for a significant subgroup of non-small cell lung cancers (NSCLC). Approximately 4-10% of EGFR mutations in NSCLC are EGFR exon 20 insertion mutations, which are reportedly associated with resistance to EGFR tyrosine kinase inhibitor (EGFR-TKI) treatment. NSCLC patients carrying these mutations are rarely treated with EGFR-TKIs. The purpose of this study was to evaluate the efficacy of afatinib or osimertinib plus cetuximab combination therapy in experimental NSCLC models with EGFR exon 20 insertion mutations. ⋯ The combination therapy induced a more potent inhibitory effect against several EGFR exon 20 insertion mutations than either therapy alone. Cetuximab can potentially increase the efficacy of afatinib or osimertinib in NSCLC with EGFR exon 20 insertion mutations.