A recent phase III trial conducted in China has demonstrated that the addition of thoracic radiotherapy to first-line EGFR tyrosine kinase inhibitor (TKI) treatment significantly improves progression-free survival and overall survival in patients with EGFR-mutated oligo-organ metastatic non-small cell lung cancer (NSCLC). The study, published in the Journal of Clinical Oncology, suggests a potential new standard of care for this patient population.
The Northern Radiation Oncology Group of China-002 trial enrolled 118 patients with EGFR-mutated oligo-organ metastatic NSCLC between April 2016 and February 2022. Patients were randomized to receive either icotinib (125 mg three times daily) until disease progression or unacceptable toxicity, with or without thoracic radiotherapy (60 Gy in 30 daily fractions) to the primary lung tumor and positive regional lymph nodes. Radiotherapy to metastases at other sites was at the discretion of clinicians. The primary endpoint was progression-free survival.
The results showed a significant improvement in median progression-free survival with the addition of thoracic radiotherapy: 17.1 months (95% CI = 11.9–23.4 months) compared to 10.6 months (95% CI = 8.8–16.6 months) with TKI treatment alone (HR = 0.57, P = .004). The 1, 3, and 5-year progression-free survival rates were 61.0% vs 47.5%, 21.3% vs 7.2%, and 11.4% vs 2.7%, respectively.
Overall survival was also significantly improved in the combination arm, with a median overall survival of 34.4 months (95% CI = 30.4–52.2 months) compared to 26.2 months (95% CI = 23.1–30.7 months) with TKI treatment alone (HR = 0.62, P = .029). The 1, 3, and 5-year overall survival rates were 91.5% vs 88.1%, 44.5% vs 27.7%, and 24.9% vs 12.8%, respectively.
Treatment-related grade 3 or 4 adverse events were more frequent in the thoracic radiotherapy plus TKI treatment arm (11.9%) compared to the TKI treatment arm (5.1%), including radiation esophagitis (6.8% vs 0%) and radiation pneumonitis (5.1% vs 0%). However, the investigators concluded that these adverse events were acceptable and tolerable.
Clinical Implications
The study suggests that the addition of thoracic radiotherapy to first-line EGFR-TKI treatment may be a beneficial strategy for patients with EGFR-mutated oligo-organ metastatic NSCLC. These findings could potentially change the treatment paradigm for this specific patient population. Further research is warranted to validate these findings in other populations and to identify the optimal patient selection criteria for this combination therapy.
According to Baosheng Li, MD, of the Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University, Jinan, corresponding author of the Journal of Clinical Oncology article, "For patients with EGFR-mutated oligo-organ metastatic NSCLC treated with first-line EGFR-TKIs, concurrent thoracic radiotherapy improves progression-free survival and overall survival, and treatment-related adverse events are acceptable and tolerable."
