Concurrent EGFR‐TKI and Thoracic Radiotherapy as First‐Line Treatment for Stage IV Non‐Small Cell Lung Cancer Harboring EGFR Active Mutations

LESSONS LEARNED. This single‐arm, phase II study shows that concurrent EGFR‐tyrosine kinase inhibitor plus thoracic radiotherapy as the first‐line treatment for stage IV non‐small cell lung cancer harboring EGFR active mutations provides long‐term control for the primary lung lesion, and 1‐year progression‐free survival (PFS) rate and median PFS are numerically higher than those of the erlotinib monotherapy. Serious adverse events are acceptable, although grade >3 radiation pneumonitis occurred in 20% of patients. BACKGROUND. Studies show effective local control by EGFR‐tyrosine kinase inhibitor (TKI) combined with radiotherapy at metastatic sites in advanced lung cancer harboring EGFR active mutations. Salvage local radiotherapy is associated with prolonged progression‐free survival (PFS) in local disease during EGFR‐TKI treatment. However, no prospective study has been reported on concurrent EGFR‐TKI and radiotherapy for primary lung lesions. This study investigated the efficacy and safety of first‐line EGFR‐TKI combined with thoracic radiotherapy in treating stage IV non‐small cell lung cancer (NSCLC) harboring EGFR active mutations. METHODS. We conducted a single‐arm, phase II clinical trial. Each patient received EGFR‐TKI (erlotinib 150 mg or gefitinib 250 mg per day) plus thoracic radiotherapy (54–60 Gy/27–30 F/5.5–6 w) within 2 weeks of beginning EGFR‐TKI therapy until either disease progression or intolerable adverse events (AEs) appeared. RESULTS. From January 2015 to March 2018, 401 patients were screened, and 10 patients (5 male and 5 female) were eligible. These patients had a median age of 55 years (40–75) and median follow‐up of 19.8 months (5.8–34). The 1‐year PFS rate was 57.1%, median PFS was 13 months, and median time to progression of irradiated lesion (iTTP) was 20.5 months. Objective response rate (ORR), was 50% and disease control rate (DCR) was 100%. The most common grade ≥3 AEs were radiation pneumonitis (20%) and rash (10%). One patient died after rejecting treatment for pneumonitis. The others received a full, systematic course of glucocorticoid therapy. Pneumonitis was all well controlled and did not relapse. CONCLUSION. Concurrent EGFR‐TKI plus thoracic radiotherapy as the first‐line treatment for stage IV NSCLC harboring EGFR active mutations shows a long‐term control of primary lung lesion. The 1‐year PFS rate and median PFS of this combined therapy are numerically higher than those of the erlotinib monotherapy. The risk of serious adverse events is acceptable.