Clinical predictors of response to EGFR-tyrosine kinase inhibitors in EGFR-mutated non-small cell lung cancer: A real-world multicentric cohort analysis from India

Abstract

Background: The development of various targeted therapies against Epidermal Growth Factor Receptor (EGFR) has been a major step in therapeutic advancements in lung cancer. However, the response to tyrosine kinase inhibitors (TKI) therapy in a real-world setting has not been well elucidated.

Methods: As part of a retrospective analysis, patients with EGFR mutated non-small cell lung cancer at 4 tertiary care Institutions in North India between December 2007 and August 2018 were evaluated. The overall response rate, disease control rate, progression-free survival (PFS) and factors affecting PFS were analyzed.

Results: A total of 483 patients were included, including 52.4% males, with mean (±SD) age of 56.7 (±12.4) years. Majority (63.8%) had good performance status (Eastern Cooperative Oncology Group 0 or 1) and 77.4% were nonsmokers. Among the EGFR mutations, exon 19 deletion was the most common mutation detected (68.1%), followed by L858R mutation in exon 21 (26.9%). Extra-thoracic metastasis was present in 69.5% patients and majority of them had ≤ 2 metastatic sites (85.1%). TKIs were used as the first-line therapy in 64.8% patients, and gefitinib was the most frequently used TKI (67.3%), followed by erlotinib (26.7%). The overall response rate and disease control rate were 65.9% and 90.7% respectively. The median PFS was 9.3 months and brain was the exclusive site of progression in 18.0% patients. On univariate analysis, the factors that significantly affected PFS were, the number of metastatic sites and the type of EGFR mutation. On multivariate analysis, the number of metastatic sites was the only factor that affected the PFS [HR (95% CI): 2.5 (1.7-3.6); Pvalue <0.001]. Skin toxicity was the most common adverse event (32.3%), followed by involvement of the gastro-intestinal tract (22.5%).

Conclusion: In this one of the largest multicentric Indian study of treatment outcomes in EGFR-mutated non-small cell lung cancer in a real-world setting, we found that increased tumor burden (number of metastatic sites > 2) was the only significant factor associated with a worse PFS.

Keywords: EGFR mutated NSCLC; PFS; TKI.