Diana Saravia

Developing a Predictive Model for Clinical Outcomes of Advanced Non-Small Cell Lung Cancer Patients Treated With Nivolumab

Micro‐Abstract A single biomarker cannot account for the heterogeneous tumor biology and immune interplay in patients with advanced non–small cell lung cancer who receive programmed death inhibitor. This article reports our initial model development that incorporates differential weightings of clinical and hematologic variables for a future algorithm. The immunotherapy, Sex, Eastern Cooperative Oncology Group performance status, Neutrophil‐to‐lymphocyte ratio (NLR), and Delta NLR are incorporated into the model that categorizes patients into different risk groups and significantly discriminates each groups clinical outcome. Introduction Despite significant improvement of clinical outcomes of advanced non–small‐cell lung cancer (NSCLC) patients treated with immunotherapy, our knowledge of optimal biomarkers is still limited. Patients and Methods We retrospectively evaluated 159 advanced NSCLC patients in our institution treated with nivolumab after disease progression during platinum‐based chemotherapy. We correlated several variables with progression‐free survival (PFS) to develop the immunotherapy, Sex, Eastern Cooperative Oncology Group performance status, Neutrophil‐to‐lymphocyte ratio (NLR), and Delta NLR (iSEND) model. We categorized patients into iSEND good, intermediate, and poor risk groups and evaluated their clinical outcomes. Performance of iSEND at 3, 6, 9, and 12 months was evaluated according to receiver operating characteristic (ROC) curves and internally validated using bootstrapping. The association of iSEND risk groups with clinical benefit was evaluated using logistic regression. Results Median follow‐up was 11.5 months (95% confidence interval [CI], 9.4‐13.1). There were 50 deaths and 43 with disease progression without death. PFS rates at 3, 6, 9, and 12 months were 78.4%, 63.7%, 55.3%, and 52.2% in iSEND good; 79.4%, 44.3%, 25.9%, and 19.2% in iSEND intermediate; and 65%, 25.9%, 22.8%, and 17.8% in iSEND poor. Time‐dependent area under ROC curves of iSEND for PFS at 3, 6, 9, and 12 months were 0.718, 0.74, 0.746, and 0.774. The iSEND poor group was significantly associated with progressive disease at 12 ± 2 weeks (odds ratio, 9.59; 95% CI, 3.8‐26.9; P < .0001). Conclusion The iSEND model is an algorithmic model that can characterize clinical outcomes of advanced NSCLC patients receiving nivolumab into good, intermediate, or poor risk groups and might be useful as a predictive model if validated independently.

Time from nephrectomy as a prognostic factor in metastatic renal cell carcinoma patients receiving targeted therapies: overall results from a large cohort of patients.

Objective: To investigate whether time from nephrectomy (Nx) to the diagnosis of metastatic disease may be an independent prognostic factor in metastatic renal cell carcinoma (mRCC) patients treated with targeted therapies (TTs). Subjects and Methods: All patients who underwent Nx and at least 1 TT were considered. The patients were divided into two groups based on time from Nx [>1 year (Nx >1) and <1 year (Nx <1)] and a third group for cytoreductive Nx (cNx). Median overall survival (OS) represented the primary outcome. Results: A total of 297 patients met the inclusion criteria. The time from Nx was >1 year in 47%, <1 year in 26% and concomitant with the diagnosis of metastatic disease in 27% of the cases (i.e. cNx). The median OS was 40.6 months (95% CI 30.5-50.7) for the Nx >1 group, 24.3 months (95% CI 17.7-31) for the Nx <1 group and 16.2 months (95% CI 11.2-21.3) for the cNx group (p < 0.05 for all comparisons). On multivariate analysis, time from Nx resulted to be an independent prognostic factor (Nx <1 vs. cNx: HR = 0.62, 95% CI 0.42-0.90, p = 0.13; Nx >1 vs. cNx: HR = 0.43, 95% CI 0.31-0.61, p < 0.001). Conclusion: We report that time from Nx is an independent prognostic factor for OS in patients affected by mRCC treated with TTs.