Introduction:The optimal management of large cell neuroendocrine cancer of the lung (LCNEC) is unclear, and data regarding anti-programmed cell death protein 1 (PD-1) antibodies are scarce. This study reports the clinical efficacy of a PD-1 inhibitor in patients with advanced LCNEC.Methods: All patients with stage III to IV LCNEC treated with at least one previous cycle of chemotherapy between January 1, 2015 and December 31, 2018 were reviewed retrospectively. Patients were divided into two groups depending on their exposure to nivolumab as second-line treatment or beyond. The primary objective was to assess nivolumab's efficacy.Results: A total of 51 patients with advanced LCNEC from eight centers were analyzed, including 17 who received nivolumab. The PD-1 inhibitor was used as second-line treatment in 77% of cases, with a median number of eight doses (range: 1-62). After nivolumab treatment, the median overall survival was 12.1 months (95% confidence interval [CI]: 7.10-14.20). The objective response rate was 29.4% (95% CI: 10.3-56.0), and median progression-free survival was 3.9 months (95% CI: 1.68-7.17). The programmed death-ligand 1 status was unknown. There was no difference in the efficacy of first-line chemotherapy; the objective response rate was 23.5% (n ¼ four of 17) in the nivolumab group versus 32.4% (n ¼ 11 of 34) in the conventional treatment group, and progression-free survival was 3.5 months (95% CI: 1.7-4.4) versus 2.1 months (95% CI: 1.4-4.2), respectively. Conclusions:In a real-world setting, nivolumab seems to be an effective second-line treatment in patients with advanced LCNEC. Large prospective studies in this setting are still required.
In this study, we evaluate the prognosis of patients with NSCLC, according to NLR and PLR, treated with ICI. Methods: Retrospective analysis of 92 patients with NSCLC treated with ICI since January 2016 until June 2020. Pre-treatment NLR and PLR were calculated by division of neutrophils and platelets by lymphocytes measured in peripheral blood. NLR ≥ 5 and PLR ≥ 150 were considered high, according to literature data. Overall survival (OS) and progression free-survival (PFS) curves were estimated using the Kaplan-Meier method.Results: From 92 patients with NSCLC treated with ICI, 65 (70.7%) were male, with a median age of 62 years (range 38-83). Seventy-eight (84.8%) had stage IV disease and 14 (15.2%) received ICI in first-line treatment. Pembrolizumab was used in 35 (38%) patients, nivolumab in 53 (57.6%) and durvalumab in 4 (4.3%). Median OS was 16.8 m (95% CI 7.98-25.60) in NLR <5 group and 5.5 m (95% CI 1.85-9.12) in NLR ≥5 group (p = 0.003). Median PFS was 9.9 m (95% CI 4.57-15.28) in NLR <5 group and 2.4 m (95% CI 0.99-3.87) in NLR ≥5 group ( p = 0.008). Cox regression analysis showed a better OS and PFS in NLR <5 group (HR = 2.43, 95% CI 1.33-4.44 and HR = 2.15, 95% CI 1.21-3.81, respectively). Median OS was 24.5 m (95% CI 6.03-43.05) in PLR <150 group and 9.4 m (95% CI 4.37-14-50) in PLR ≥150 group ( p = 0.041). Conclusions: Elevated pre-treatment NLR and PLR were associated with worse outcomes. Our results are in agreement with previous studies showing that inflammation markers are potential predictors of response in ICI treated patients. Prospective studies are required to validate these findings.
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