Addition of Concurrent Thoracic Radiotherapy to First-Line TKI Therapy Improves Survival for Patients With EGFR-Mutated Non-Small Cell Lung Cancer

According to results from a phase 3 trial, the addition of concurrent thoracic radiotherapy to treatment with first-line icotinib, a first-generation tyrosine kinase inhibitor (TKI), improved survival among patients with epidermal growth factor receptor (EGFR)-mutated oligo-organ metastatic non-small cell lung cancer (NSCLC). 

“The National Comprehensive Cancer Network NSCLC Panel recommends EGFR-TKIs as the first-line therapy option for patients with EGFR-mutated metastatic NSCLC… [however] <40% of patients with metastatic NSCLC receive local treatment, and more than 60% would experience intrathoracic disease progression,” stated Hongfu Sun, MD, Shandon Cancer Hospital and Institute, Jinan, China, and coauthors. 

In this multicenter trial, 118 pre-treated patients were randomized on a 1-to-1 basis to receive 125 mg of icotinib 3 times per day either alone (n = 59) or in combination with thoracic radiotherapy at 60 Gy in 30 daily fractions to the primary lung tumor and positive regional lymph nodes (n = 59) until disease progression or unacceptable toxicity. The primary end point was progression-free survival (PFS). Key secondary end points included overall survival (OS) and incidence of treatment-related adverse events. 

At a median follow-up of 27.53 months, the median PFS was 10.6 months in the icotinib alone arm and 17.1 months in the icotinib plus thoracic radiotherapy arm (hazard ratio [HR], 0.566; P = .004). The median OS was 26.2 months and 34.4 months, respectively (HR, 0 .623; P = .029). Grade 3/4 adverse events occurred in 5.1% of patients in the icotinib alone arm and 11.9% of patients in the icotinib plus thoracic radiotherapy arm. The most common treatment-related adverse events included skin rash, leukopenia, neutropenia, and diarrhea. In the icotinib plus thoracic radiotherapy arm patients experienced severe radiation esophagitis, severe radiation pneumonitis, and severe leukopenia or neutropenia. 

As Dr Sun et al concluded, this regimen “could significantly improve survival for patients with EGFR-mutated oligo-organ metastatic NSCLC than the TKI alone regimen,” concluded Dr Sun et al. 

“Confirmation of these results and investigation of how irradiation impacted tumor control will improve management of primary and metastatic lung cancers with driver mutations for which active targeted therapies are available,” added Journal of Clinical Oncology Associate Editor Jonathan Knisely, MD, Weill Cornell Medicine, New York, New York. 

Source: 

Sun H, Li M, Huang W, et al. Thoracic radiotherapy improves the survival in patients With EGFR-mutated oligo-organ metastatic non–small cell lung cancer treated with epidermal growth factor receptor–tyrosine kinase inhibitors: A multicenter, randomized, controlled, phase III trial. J Clin Oncol. Published online: October 7, 2024. doi: 10.1200/JCO.23.02075