Primary lesion radiotherapy during first-line icotinib treatment in EGFR-mutated NSCLC patients with multiple metastases and no brain metastases: a single-center retrospective study.

Background: The most frequent mode of progression in the majority of non-small cell lung cancer (NSCLC) patients treated with  Epidermal growth factor - receptor tyrosine kinase inhibitors (EGFR-TKIs) is failure to respond to treatment at the primary lesion, suggesting that concurrent radiotherapy (CRT) to the primary lesion (CPRT) during first-line treatment with EGFR-TKI may be a novel therapeutic approach with a potential of additional benefit for metastatic NSCLC. Therefore, this study investigated the progression-free survival (PFS) and safety of CPRT during first-line icotinib treatment in NSCLC patients with EGFR mutations.

Methods: EGFR-mutant NSCLC patients diagnosed with limited multiple metastases were treated with first-line icotinib. The decision to treat the primary lesions with radiation largely depended on the patient's preference. The study endpoints included PFS, toxicity, progression pattern, and acquisition of the T790M mutation.

Results: The median PFS in the CPRT and Non-CPRT groups was 13.6 and 10.6 months (hazard ratio [HR] 0.23, 95% confidence interval [CI] 0.15-0.37, P < 0.001). Subgroup analysis showed that the results were statistically significant with 14.7 and 11.5 months for the 19del mutation (HR 0.20, 95% CI 0.10-0.40, P < 0.001) and 12.9 and 9.9 months for the L858R mutation (HR 0.25, 95% CI 0.13-0.48, P < 0.001). There were no reports of interstitial pneumonia associated with treatment at grade 4 or above. Patients who received CPRT during first-line icotinib treatment had the potential to decrease the primary lesion progression (P < 0.05) without increasing newly metastatic lesions (P > 0.05). The proportion of acquired T790M mutations was 26.7% and 45.7% in both groups (P > 0.05).

Conclusion: This study suggests that CPRT is a viable option for patients with EGFR-sensitive mutations in NSCLC with limited multiple metastases during first-line icotinib treatment, which can significantly improve PFS with acceptable toxicities. Data on progression patterns and T790M mutations suggest the need to further investigate the benefits of radiation treatment from a molecular perspective.