Prognostic Value of Clinical Staging According to TNM in Patients With SCLC: A Real-World Surveillance Epidemiology and End-Results Database Analysis.

INTRODUCTION: SCLC is one of the most lethal malignancies. Classically, staging has been performed using a dual classification distinguishing limited from the extensive stage. This study aimed to evaluate the prognostic value of TNM staging in a real-world population of patients with SCLC. METHODS: Patients were selected from the Surveillance Epidemiology and End Results database. Chi-square bivariate analysis was used for the association of binary qualitative variables. A multivariate Cox regression analysis was performed to determine the impact of these prognostic factors on median overall survival (mOS) and long-term survival. RESULTS: A total of 26,221 patients were included (50.7% men, 55.7% ≥65 y, 82% White). At diagnosis, 18,574 (70.83%) presented metastases, which were more frequent in the liver (n = 11,896, 64%). In the overall population, mOS was 8 (7.86-8.14) months, which decreased according to each increasing category of TNM staging (p < 0.0001). The worse mOS was found among patients with stage IV SCLC (6 mo, 95% confidence interval: 5.83-6.17). Long-term survival decreased according to TNM staging, with patients having stage IV SCLC exhibiting the lowest survival rates at all follow-up time points. Within stage IV, the lowest mOS values were found in patients greater than or equal to 65 years and in those with liver metastases. Among the TNM stages corresponding to the limited stage, stage IB revealed the lowest hazard ratios value for risk of death compared with stage IA (hazard ratio = 1.161, 95% confidence interval: 0.97-1.40, p = 0.114), which increased gradually within the limited-stage SCLC. In the multivariate analysis, TNM staging, male sex, and older age resulted in poor prognostic factors for survival. CONCLUSIONS: TNM staging seems to define prognosis in patients with SCLC in the real-world setting, particularly for those patients with earlier disease.

Addition of Immune Checkpoint Inhibitors to Chemotherapy vs Chemotherapy Alone as First-Line Treatment in Extensive-Stage Small-Cell Lung Carcinoma: A Systematic Review and Meta-Analysis.

INTRODUCTION: The addition of immune checkpoint inhibitors (ICIs) to conventional chemotherapy (CT) as first-line treatment improves survival in extensive-stage small-cell lung cancer (ES-SCLC). The aim of this meta-analysis was to determine the relative efficacy of first-line ICIs compared with CT in patients with ES-SCLC. METHODS: Two independent reviewers extracted relevant data according to PRISMA guidelines and assessed the risk of bias using the Cochrane Collaboration's risk-of-bias tool. Meta-analysis was conducted using random-effects models to calculate an average effect size for overall survival (OS), progression-free survival (PFS), and safety outcomes in the overall populations and clinically relevant subgroups. RESULTS: A literature search of PubMed and Embase was performed. Six randomized controlled clinical trials (IMpower133, CHECKMATE-451, CASPIAN, KEYNOTE-604, and phase II and III ipilimumab plus CT trials) with a total of 3757 patients were included. Compared with CT alone, ICIs plus CT showed a favourable effect on OS (hazard ratio [HR] 0.85; 95% confidence intervals [CI] 0.79-0.96) and PFS (HR 0.78; 95% CI 0.72-0.83) but a non-significant increase in the risk of experiencing any adverse event (relative risk, 1.05; 95% CI 0.99-1.11). The estimated HR for OS favoured ICI combinations in all planned subgroups according to age (< 65 years/≥ 65 years), sex (men/women), and ECOG performance status (0/1). Analysis by specific ICI revealed significant improvements in OS only for atezolizumab + CT (HR 1.36; 95% CI 1.09-1.69) and durvalumab + CT (HR 1.35; 95% CI 1.12-1.62) compared with CT alone. CONCLUSION: Combining anti-programmed cell death ligand 1 antibodies with platinum/etoposide is a superior therapeutic approach compared to CT alone for the first-line treatment of patients with ES-SCLC.

Prognostic factors for survival in patients with metastatic lung adenocarcinoma: An analysis of the SEER database.

BACKGROUND: Lung adenocarcinoma (ADC) is the main cause of death related to lung cancer. The aim of this study was to identify poor prognostic factors for overall survival (OS) in patients with stage IV lung ADC in real-world clinical practice. METHODS: Patients were selected from the Surveillance Epidemiology and End Results (SEER) database. Chi-square bivariate analysis was used for the association of binary qualitative variables. A multivariate Cox regression analysis was performed to determine the impact of these prognostic factors on OS. RESULTS: A total of 46 030 patients were included (51.3% men, mean age 67.03 ± 11.6), of whom 41.3% presented with metastases in bone, 28.9% in brain, 17.1% in liver and 31.8% in lung. Patients with liver metastases presented with two or more metastatic sites more frequently than patients without liver metastases (P < 0.001). Male sex (HR 0.78, 95% CI: 0.76-0.80), age ≥ 65 years (HR 1.37, 95% CI: 1.33-1.40), lack of family support (HR 0.80, 95% CI: 0.78-0.81) and presence of liver (HR 1.45, 95% CI: 1.40-1.50), bone (HR 1.21, 95% CI: 1.18-1.24) or brain metastases (HR 1.18, 95% CI: 1.15-1.21) were identified as poor prognostic factors for OS. Patients with liver metastasis showed the highest hazard ratio value (P < 0.001). CONCLUSIONS: The presence of liver metastases was the worst prognostic factor for patients with metastatic lung ADC. This factor should be considered as a stratification factor for future studies evaluating new cancer treatments including immunotherapy. KEY POINTS: SIGNIFICANT FINDINGS OF THE STUDY: Regression analysis identified poor prognostic factors for overall survival. Factors were male sex, age ≥ 65 years, lack of family support and presence of liver, bone and brain metastases. Patients with liver metastasis showed the highest HR (HR = 1.45 95% CI: 1.40-1.50). This study included the highest number of adenocarcinoma patients analyzed so far (N = 46 030). What this study adds The presence of liver metastases should be considered as a stratification factor for future studies evaluating new cancer treatments including immunotherapy.

PD-(L)1 Inhibitors in Combination with Chemotherapy as First-Line Treatment for Non-Small-Cell Lung Cancer: A Pairwise Meta-Analysis.

The combination of programmed cell death-1 (PD-1)/programmed death ligand-1 (PD-L1) inhibitors with chemotherapy has emerged as a promising therapeutic option for advanced non-small-cell lung cancer (NSCLC). The aim of this meta-analysis was to evaluate the efficacy of the combined strategy in this setting. For this purpose, we performed a literature search of randomized controlled trials comparing PD-(L)1 inhibitors plus platinum-based chemotherapy versus chemotherapy alone in stage IV NSCLC patients. Seven clinical trials with 4562 patients were included. In the intention-to-treat wildtype population, PD-(L)1 inhibitor plus chemotherapy was significantly associated with improved progression-free survival (PFS) (Hazard ratio (HR) = 0.61, 95% confidence interval (CI): 0.57-0.65, p < 0.001) and overall survival (OS) (HR = 0.76, 95% CI: 0.67-0.86; p < 0.001) compared to chemotherapy. A significantly higher overall response rate (ORR) was also observed with the combined strategy (Odds ratio (OR) = 2.12, 95% CI: 1.70-2.63, p < 0.001). Furthermore, in all the analyzed subgroups, addition of PD-(L)1 inhibitors to chemotherapy significantly improved efficacy endpoints. Specifically, stratification according to PD-L1 expression revealed a benefit across all patients, regardless of their PFS status. In conclusion, PD-(L)1 blockade added to standard platinum-based chemotherapy significantly improved PFS, OS, and ORR in the up-front treatment of advanced NSCLC.