Pembrolizumab for First-Line Treatment of Advanced Non-Small-Cell Lung Cancer: Analysis of Prognostic Factors of Outcomes

Abstract

Background: In advanced non-small-cell lung cancer, without activating mutations and with PD-L1≥50%, Pembrolizumab monotherapy is the therapeutic standard in Europe. Objective: to evaluate retrospectively the safety and the efficacy of this drug and to investigate potential prognostic factors in daily clinical practice. Methods: From September 2017 to September 2019, 205 consecutive patients from 14 Italian Medical Oncology Units were enrolled in the study. Gender, Age (> or <70 years), ECOG-PS (0-1 or 2), histology (squamous or non-squamous), presence of brain, bone and liver metastases at baseline, PD-L1 score (>90% or <90%), smoking status (never or former or current) were applied to the stratified log-rank. Cox’s proportional hazards model was used for multivariate analysis. Results: At a median follow-up of 15.2 months, median progression-free and overall survival (mPFS and mOS) were 9.2 months (95% C.I., 4.8-13.5) and 15.9 months (95% C.I., not yet evaluable), respectively. Patients with Eastern Cooperative Oncology Group performance status (ECOG-PS) 2 had mPFS of 2.8 months (95% C.I., 2.1-3.4) and mOS of 3.9 months (95% C.I., 2.5-5.3). Patients with liver metastases at diagnosis had an mPFS of 3.2 months (95% C.I., 0.6-5.8) and an mOS of 6.0 months (95% C.I., 3.7-8.4). At multivariate analysis for OS gender, ECOG-PS 2, and presence of liver metastases were independent prognostic factors. Conclusion: Patients with ECOG-PS 2 derived little benefit from the use of first-line pembrolizumab. In patients with liver metastases the association of pembrolizumab with platinum-based chemotherapy could be a better option than pembrolizumab alone.

EZH2 Inhibition Enhances PD‐L1 Protein Stability Through USP22‐Mediated Deubiquitination in Colorectal Cancer

“…[ 3 ] However, only 20–40% of patients respond to ICIs, and even fewer will have long‐term disease remission. [ 4 , 5 , 6 , 7 ] Various indicators, including PD‐L1 (including exo PD‐L1), TMB, high microsatellite instability (MSI‐H), and mismatch repair‐deficient (dMMR), are considered capable of predicting populations who would benefit from immunotherapy. Generally, the level of PD‐L1 expression is widely considered as a potential biomarker of anti‐PD‐1/PD‐L1 immunotherapy.…”