A nomogram to predict survival in non-small cell lung cancer patients treated with nivolumab

Abstract

Background The advent of immune checkpoint inhibitors (ICIs) has considerably expanded the armamentarium against non-small cell lung cancer (NSCLC) contributing to reshaping treatment paradigms in the advanced disease setting. While promising tissue- and plasma-based biomarkers are under investigation, no reliable predictive factor is currently available to aid in treatment selection. Methods Patients with stage IIIB–IV NSCLC receiving nivolumab at Sant’Andrea Hospital and Regina Elena National Cancer Institute from June 2016 to July 2017 were enrolled onto this study. Major clinicopathological parameters were retrieved and correlated with patients’ survival outcomes in order to assess their prognostic value and build a useful tool to assist in the decision making process. Results A total of 102 patients were included in this study. The median age was 69 years (range 44–85 years), 69 (68%) were male and 52% had ECOG PS 0. Loco-regional/distant lymph nodes were the most commonly involved site of metastasis (71%), followed by lung parenchyma (67%) and bone (26%). Overall survival (OS) in the whole patients’ population was 83.6%, 63.2% 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 ( P = 0.057), ECOG PS ( P < 0.001), the presence of liver ( P < 0.001), lung ( P = 0.017) metastases, lymph nodes only involvement (P = 0.0145) were significantly associated with OS and ECOG PS ( P < 0.001) and liver metastases ( P < 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.

The Agnostic Role of Site of Metastasis in Predicting Outcomes in Cancer Patients Treated with Immunotherapy

“…However, in the novel context of immunotherapy and immune biomarkers, the liver site of metastasis appears to play a relevant negative predictive role in tumor response. In particular, it was demonstrated that the poor response to immunotherapy is associated with liver metastasis in melanoma patients treated with ipilimumab and nivolumab [ 45 ] and in NSCLC patients treated with nivolumab [ 43 , 44 ]. The peculiar immunological behavior of patients with liver metastases could be related to the immunological context of liver microenvironment that seems to be ‘colder’ than the primary tumor or than another metastatic site such as lung or lymph node.…”

“…In this scenario, we have already performed a nomogram to predict response to nivolumab in a lung cancer cohort of patients [ 44 ].…”

Tryptophan Catabolism as Immune Mechanism of Primary Resistance to Anti-PD-1

“…Recently, in a large retrospective study including NSCLC in treatment with immunotherapy, lymph node metastases were associated with the best response, lung and pleura metastases were associated with an intermediate response, and liver, which expressed TDO at high levels, and bone metastases were associated with the least responses to immunotherapy ( 38 ). In a study including 102 patients with NSCLC in treatment with nivolumab, lung and liver metastases have been proven to be excellent parameters in predicting OS ( 39 ). Consequently, metastatic sites could have an impact on the development of primary resistance to immunotherapy ( 40 ), but the underlying biological mechanism should be further investigated, and our study must be considered as a hypothesis generator.…”

Development and Validation of an Individualized Nomogram for Predicting Overall Survival in Patients With Typical Lung Carcinoid Tumors

“…The nomograms constructed by Guo et al 26 may be valuable for the precise evaluation of patient prognosis and the development of further treatment against locally advanced NSCLC, achieving a c -index of 0.692 and an AUC of 0.742. In addition, Botticelli et al 27 have developed a nomogram for NSCLC patients treated with nivolumab, which can accurately drive treatment strategies with a c -index of 0.76. One study 28 constructed nomograms based on gene expression data or more complex information, not limited to clinical statistics.…”