Tumor immune microenvironment and nivolumab efficacy in EGFR mutation-positive non-small-cell lung cancer based on T790M status after disease progression during EGFR-TKI treatment
| Autor: | Yosuke Togashi, K. Tanimura, Kazuhiko Nakagawa, Kaoru Tanaka, Hidetoshi Hayashi, Kazuko Sakai, Ken-ichiro Hayashi, Kimio Yonesaka, Takayuki Takahama, Masayuki Takeda, Hiroyasu Kaneda, Takeshi Yoshida, Koji Haratani, Yoshikane Nonagase, Tetsuya Mitsudomi, Tae Tanaka, Tadashi Ishida, Hiroshige Yoshioka, Junko Tanizaki, Shuta Tomida, Kazuto Nishio, Yasutaka Chiba |
|---|---|
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Oncology Male Lung Neoplasms Time Factors Kaplan-Meier Estimate B7-H1 Antigen T790M 0302 clinical medicine Antineoplastic Agents Immunological Carcinoma Non-Small-Cell Lung Tumor Microenvironment Epidermal growth factor receptor Precision Medicine Aged 80 and over biology Antibodies Monoclonal Hematology Middle Aged Resistance mutation ErbB Receptors Nivolumab Phenotype Treatment Outcome Editorial 030220 oncology & carcinogenesis Cohort Disease Progression Female Adult medicine.medical_specialty Disease-Free Survival 03 medical and health sciences Lymphocytes Tumor-Infiltrating PD-L1 Internal medicine medicine Humans Genetic Predisposition to Disease Lung cancer Protein Kinase Inhibitors Aged Retrospective Studies Tumor-infiltrating lymphocytes business.industry Patient Selection medicine.disease respiratory tract diseases 030104 developmental biology Drug Resistance Neoplasm Immunology Mutation biology.protein business |
| Zdroj: | Annals of oncology : official journal of the European Society for Medical Oncology. 28(7) |
| ISSN: | 1569-8041 |
| Popis: | The efficacy of programmed death-1 blockade in epidermal growth factor receptor gene (EGFR) mutation-positive non-small-cell lung cancer (NSCLC) patients with different mechanisms of acquired resistance to EGFR tyrosine kinase inhibitors (TKIs) is unknown. We retrospectively evaluated nivolumab efficacy and immune-related factors in such patients according to their status for the T790M resistance mutation of EGFR.We identified 25 patients with EGFR mutation-positive NSCLC who were treated with nivolumab after disease progression during EGFR-TKI treatment (cohort A). Programmed death-ligand 1 (PD-L1) expression and tumor-infiltrating lymphocyte (TIL) density in tumor specimens obtained after acquisition of EGFR-TKI resistance were determined by immunohistochemistry. Whole-exome sequencing of tumor DNA was carried out to identify gene alterations. The relation of T790M status to PD-L1 expression or TIL density was also examined in an independent cohort of 60 patients (cohort B).In cohort A, median progression-free survival (PFS) was 2.1 and 1.3 months for T790M-negative and T790M-positive patients, respectively (P = 0.099; hazard ratio of 0.48 with a 95% confidence interval of 0.20-1.24). Median PFS was 2.1 and 1.3 months for patients with a PD-L1 expression level of ≥1% or 1%, respectively (P = 0.084; hazard ratio of 0.37, 95% confidence interval of 0.10-1.21). PFS tended to increase as the PD-L1 expression level increased with cutoff values of ≥10% and ≥50%. The proportion of tumors with a PD-L1 level of ≥10% or ≥50% was higher among T790M-negative patients than among T790M-positive patients of both cohorts A and B. Nivolumab responders had a significantly higher CD8+ TIL density and nonsynonymous mutation burden.T790M-negative patients with EGFR mutation-positive NSCLC are more likely to benefit from nivolumab after EGFR-TKI treatment, possibly as a result of a higher PD-L1 expression level, than are T790M-positive patients. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|