Programmed cell death‐ligand 1 (PD‐L1) expression and fibroblast growth factor receptor 1 (FGFR1) amplification in stage III/IV lung squamous cell carcinoma (SQC)

Abstract

BackgroundThis study was conducted to explore programmed cell death‐ligand‐1 (PD‐L1) expression and fibroblast growth factor receptor 1 (FGFR1) amplification in stage IIIB/IV lung squamous cell carcinoma (SQC). Correlations between PD‐L1 and FGFR1, and with clinicopathological characteristics, efficacy of platinum‐based chemotherapy, and prognosis were analyzed.MethodsOne hundred and twenty‐eight consecutive stage III/IV SQC patients were enrolled in this study from 2009 to 2014. Seventy‐eight patients received platinum‐based chemotherapy. Immunohistochemistry was used to assess PD‐L1 expression and fluorescence in situ hybridization was applied to detect FGFR1 amplification.Results PD‐L1 expression was detected in 61.7% (79/128) of lung SQC patients. Smokers had significantly higher PD‐L1 expression rates than non‐smokers (66.1% vs. 44.0%, P = 0.042, respectively). The objective response and disease control rates for platinum‐based chemotherapy were not significantly different between PD‐L1 negative and positive patients (43.3% vs. 36.2%, P = 0.434; 80.0% vs. 78.7% P = 0.840, respectively); however, overall survival in PD‐L1‐negative patients was significantly longer than in PD‐L1‐positive patients (41.5 vs. 19.3 months, P = 0.001). Twenty‐five percent (32/128) of patients displayed FGFR1 amplification, with a lower rate in stage III patients compared to stage IV (17.1% vs. 36.5%, P = 0.013, respectively). There was no significant difference in FGFR1 amplification levels between overall response, disease control or overall survival rates. No correlation was observed between PD‐L1 expression and FGFR1 amplification (P = 0.916).Conclusion PD‐L1 expression may function as a prognostic factor in Chinese stage III/IV SQC patients. FGFR1 amplification is more prevalent in late stage SQC patients but does not predict chemotherapy response. There is no apparent correlation between PD‐L1 expression and FGFR1 amplification.

Aligning digital CD8+ scoring and targeted next‐generation sequencing with programmed death ligand 1 expression: a pragmatic approach in early‐stage squamous cell lung carcinoma

“…Accordingly, it has been proposed that scoring of PD‐L1 ICs may increase the accuracy of PD‐L1 expression . In agreement with our results, high copy number levels of MYC have been shown to induce PD‐L1 expression in several tumour types, but there is no positive correlation between FGFR1 amplification and PD‐L1 expression in lung SCCs . Remarkably, our finding concerning the highest percentages of PD‐L1‐positive TCs being found in the patient with CDK6 amplification replicates gene expression profiling data, in which up‐regulation of PD‐L1 and CDK6 overlapped perfectly in the same group of SCCs …”

Phase III Non-inferiority Study Evaluating Efficacy and Safety of Low Dose Gemcitabine Compared to Standard Dose Gemcitabine With Platinum in Advanced Squamous Lung Cancer

“…The current NCCN guidelines recommend treatment with systemic chemotherapy if driver mutation status (EGFR, ALK, ROS-1, BRAF) is negative or unknown and PDL1 expression is below 50% in squamous cell NSCLC requiring palliative systemic therapy [1]. The cumulative incidence of presence of these mutations status is in the range of 10–15% [25], [26] and PDL1 expression above 50% is seen in 18% of patients [27], [28], [29], [30], [31], [32]. Hence, despite recent advances in the treatment of NSCLC, majority of the patients (> 50%) are only eligible for systemic chemotherapy.…”

Programmed death ligand 1 expression in early stage, resectable non-small cell lung cancer

“…A plethora of clinical trials are evaluating the combination of immunotherapy with chemotherapy, target therapies or other immune-directed agents; other trials are exploring immunotherapy in the neoadjuvant and adjuvant settings [46-48]. Although PD-L1 expression seems predictive for sensitivity to anti-PD-1/PD-L1 strategies, its prognostic impact remains unclear in early as well as in advanced disease [9, 10, 12, 13-15, 17, 19, 21-23, 25-28, 35-40].…”