Network meta-analysis of first-line systemic regimens for older patients with advanced NSCLC.

Various immunotherapy treatments have received approval for the treatment of advanced non-small cell lung cancer (NSCLC), either as standalone or in conjunction with chemotherapy, contingent upon the extent of PD-L1 expression. These treatments are commonly utilized in clinical practice. However, a specific gap exists in direct comparisons of these regimens in elderly patients. The aim of this network meta-analysis (NMA) was to examine the effectiveness of PD-1/PD-L1 inhibitors, either alone or in conjunction with chemotherapy, as the initial treatment for elderly patients diagnosed with advanced NSCLC. We extensively searched PubMed, EMBASE and the Cochrane Library to gather randomized clinical trials that utilized PD-1/PD-L1 inhibitors as the first-line therapy for advanced NSCLC. By means of Bayesian NMA, we conducted an analysis on hazard ratios (HRs) related to overall survival (OS). A total of 5240 patients were included in the 21 trials. Across all studies, cemiplimab exhibited a noteworthy superiority to chemotherapy in terms of OS [HR = 0.48, 95% confidence interval (CI): 0.3-0.77]. In the subgroup analysis, it was observed that patients with PD-L1 expression of 50% or higher experienced the greatest OS benefit from cemiplimab (HR = 0.48, 95% CI: 0.3-0.77). Conversely, the cohort with unselected PD-L1 scores (>1 or any score) exhibited the greatest OS benefit when treated with pembrolizumab combined with chemotherapy, as indicated by a HR of 0.69 (95% CI: 0.52-0.9). Chemotherapy combined with pembrolizumab and cemiplimab monotherapy may represent the reference regimens for older patients with NSCLC with unselected and >50% PD-L1 expression, respectively.

Targeting HER2 heterogeneity in breast and gastrointestinal cancers.

About 20% of breast and gastric cancers and 3% of colorectal carcinomas overexpress the human epidermal growth factor receptor 2 (HER2) and are sensitive to HER2-directed agents. The expression of HER2 may differ within the same tumoral lesion (spatial intralesional heterogeneity), from different tumor locations (spatial interlesional heterogeneity), and throughout treatments (temporal heterogeneity). Spatial and temporal heterogeneity may impact on response and resistance to HER2-targeting agents and its prevalence and predictive role changes across HER2-overexpressing solid tumors. Therefore, the definition and the characterization of HER2 heterogeneity pose many challenges and its implementation as a reproducible predictive biomarker would help in guiding treatment modulation.