The presence of lung metastases corresponds to 20 points, the presence of liver metastases corresponds to 0 points, while the ECOG PS of 1 1 corresponds to 50 points. and 46.9% at 3, 6 and 12?months, respectively; while progression-free survival (PFS) was 66.5%, 44.4% and 26.4% at 3, 6 and 12?months, respectively. At univariate analysis, age??69?years ( em P? /em =?0.057), ECOG PS ( em P? /em ?0.001), the presence of liver ( em P? /em ?0.001), lung ( em P? /em =?0.017) metastases, lymph nodes only involvement (P?=?0.0145) were significantly associated with OS and ECOG PS ( em P? /em ?0.001) and liver metastases ( em P? /em ?0.001), retained statistical significance at multivariate analysis. A prognostic nomogram based on three variables (liver and lung metastases and ECOG PS) was built to assign survival probability at 3, 6, and 12?months after nivolumab treatment commencement. Conclusion We developed a nomogram based on easily available and inexpensive clinical factors showing a good performance in predicting individual OS probability among NSCLC patients treated with nivolumab. This prognostic device could be valuable to clinicians in more accurately driving treatment decision in daily practice as well as enrollment onto clinical trials. strong class=”kwd-title” Keywords: Immunotherapy, Lung cancer, Prognostic factors, Nivolumab, Nomogram Background Lung cancer represents a massive health burden worldwide with 1.7 million deaths annually and Radequinil a 26% increase in incidence during the last decade [1]. More than a half of patients present with stage IV disease and less than 5% of them survive beyond 5?years [2]. The introduction of immune checkpoint inhibitors (ICI) has considerably expanded the armamentarium against non-small cell lung cancer (NSCLC) contributing to reshaping treatment paradigms in the advanced disease setting [3, 4]. The anti-PD-1 pembrolizumab both as monotherapy and combined with platinum/pemetrexed doublet is considered a first-line treatment option in PD-L1 overexpressing (?50%) [5] and unselected patients [6], respectively, in absence of actionable oncogenic drivers. Moreover, the anti-PD-L1 atezolizumab has emerged as a further front-line therapeutic choice both in combination with bevacizumab, carboplatin and paclitaxel [7] and platinum-based doublets [8] in NSCLC regardless of PD-L1 status. In the second-line setting, nivolumab [9] and atezolizumab [10] (irrespective Radequinil of PD-L1 expression) and pembrolizumab (PD-L1??1%) [11] are approved as single-agent for chemotherapy pretreated, immunotherapy-na?ve patients. The fast-growing number of immunotherapeutics and their limited efficacy with 70C80% of patients progressing within the first 2C3?months underline the need for predictive biomarkers aiding in treatment selection [12]. Moreover, a subset of patients termed as hyperprogressors and ranging from 9 to 29% have been described that experience a paradoxically accelerated tumour growth while on ICI treatment [13]. Tumour-associated macrophages reprogramming towards a pro-tumorigenic Rabbit Polyclonal to Galectin 3 phenotype upon Fc receptor engagement by ICI has been suggested to have a causative role in this phenomenon in patients with distinctive immune and genetic profiles. Nivolumab is a fully human IgG4 anti-PD1 monoclonal antibody that showed to prolong OS compared to docetaxel in NSCLC failing first-line chemotherapy. However, it yielded a response rate as low as 13.6% to 23% and a median PFS of 2.3 to 4 4?months in biomarker-unselected patients [9, 10]. Several biomarkers are being studied that can help to enrich for patients more likely to benefit from nivolumab Radequinil [14, 15]. PD-L1 is a suboptimal predictive biomarker since less than 50% of PD-L1-selected patients respond to treatment and some responders may be encountered also in biomarker-negative cohorts. Tumour mutational burden (TMB) holds great promise and up to now is the sole clinically validated biomarker. Nevertheless, no consensus exists on how it should be measured and its widespread use is thus limited. Additional promising tissue- and plasma-based predictive biomarkers are under investigation, including tumour infiltrating lymphocytes, immunoscore (composite biomarker integrating four T cell related IHC features), immune gene signatures, eosinophil, lymphocyte and neutrophil counts and relative ratios from peripheral blood, plasma IL-6 and IDO, microsatellite instability status, interferon signature, T cell repertoire, MHC status and microbiome profile [14]. Among clinical factors, poor performance status (ECOG PS??2), a period of time since prior treatment??6?months and involvement of more than one metastatic site have been independently associated with shorter OS in a cohort of 175 pretreated NSCLC patients receiving nivolumab [16]. More recently, ECOG PS??2, liver and lung metastases have been suggested to be independent predictors of nivolumab efficacy in an Asian population of 201 advanced NSCLC [17]. The aim of our study is to assess the predictive-prognostic significance of clinicopathological parameters in NSCLC patients receiving second-line nivolumab treatment in clinical practice in order to build.
