Journal Article

Real-world progression-free survival (rwPFS) and the impact of PD-L1 and smoking in driver-mutated non-small cell lung cancer (NSCLC) treated with immunotherapy

Clapper, Margie L., Ross, Eric A., Treat, Joseph, Handorf, Elizabeth A., Bauman, Jessica R., Bodor, J. Nicholas

2023

Overview

Purpose Prior data suggest driver-mutated NSCLC, especially EGFR and ALK tumors, poorly respond to immunotherapy. However, little research using real-world cohorts have been performed, nor is it clear whether PD-L1 and smoking history are predictive of outcomes in such tumors. This study assessed rwPFS in a large cohort with driver-mutated advanced NSCLC treated with single-agent PD-1/PDL-1 inhibitors. Methods Real-world data from 1746 patients were analyzed and rwPFS with immunotherapy was determined for EGFR, ALK, BRAF, and KRAS tumors. Kaplan–Meier curves characterized rwPFS and correlated with PD-L1 and smoking history. Comparisons were tested using log-rank. Results Median rwPFS and the percent progression-free at 12 months were greater among KRAS (3.3 months, 21.1%) and BRAF (3.6 months, 20.6%) as compared to EGFR (2.5 months, 8.1%) and ALK tumors (2.3 months, 11.2%). KRAS tumors with PD-L1 ≥ 1% had longer rwPFS than PD-L1 < 1% tumors (4.1 versus 3.2 months, p  = 0.001). PD-L1 positivity did not predict rwPFS in EGFR, ALK, or BRAF tumors. However, a smoking history was associated with longer rwPFS in EGFR (2.6 versus 2.3 months, p  = 0.048) and ALK tumors (3.0 versus 2.1 months, p  = 0.049) as compared to no smoking history. Conclusion Real-world PFS with immunotherapy was greater in KRAS and BRAF as compared to EGFR and ALK tumors. PD-L1 positivity was predictive in KRAS and not associated with rwPFS in other mutation types. While median rwPFS was short for EGFR and ALK tumors, small subsets were progression-free at 12 months. Better characterizing these subsets that benefit, along with developing strategies to overcome immunotherapy resistance in EGFR/ALK tumors are needed.

• Publisher: Springer Berlin Heidelberg,Springer Nature B.V
• Subject: B7-H1 Antigen - metabolism / Cancer Research / Carcinoma, Non-Small-Cell Lung - genetics / Carcinoma, Non-Small-Cell Lung - metabolism / Carcinoma, Non-Small-Cell Lung - therapy / Epidermal growth factor receptors / ErbB Receptors - genetics / ErbB Receptors - metabolism / Hematology / Humans / Immunotherapy / Internal Medicine / K-Ras protein / Lung cancer / lung neoplasms / Lung Neoplasms - genetics / Lung Neoplasms - metabolism / Lung Neoplasms - therapy / Medicine / Medicine & Public Health / Mutation / Non-small cell lung carcinoma / Oncology / Original Article – Clinical Oncology / PD-1 protein / PD-L1 protein / Progression-Free Survival / Proto-Oncogene Proteins B-raf - genetics / Proto-Oncogene Proteins B-raf - metabolism / Proto-Oncogene Proteins p21(ras) - genetics / Receptor Protein-Tyrosine Kinases - genetics / Small cell lung carcinoma / Smoking / Tumors