Upfront Local Radiation Therapy and First-Line TKI versus TKI Alone in Previously Untreated EGFR-Mutated Oligometastatic NSCLC

Improved progression-free survival and overall survival in patients who received upfront stereotactic radiotherapy and TKI treatment should prompt additional study.

Possible outcomes of treatment with aggressive local therapy in patients with oligometastatic non–small-cell lung cancer (NSCLC) are unknown. The effect of treating previously untreated patients with EGFR-mutated (EGFRm) oligometastatic NSCLC with upfront stereotactic radiotherapy on progression-free survival (PFS) and overall survival (OS) was assessed in a multi-institutional, randomized, open-label phase 3 clinical trial.

The 5-center study was conducted in various provinces throughout China. Patients eligible for the trial had pathologically confirmed stage IV adenocarcinoma, EGFRm confirmed by sequencing, ≤5 metastatic disease lesions, an Eastern Cooperative Oncology Group performance status of ≤2, no previous treatments, and no brain disease. Randomized cohorts received either a dual treatment of upfront stereotactic radiotherapy to all sites of disease along with first-line tyrosine kinase inhibitor (TKI) treatment or first-line TKI treatment alone. The primary and secondary end points were PFS and OS, respectively.

Of 133 enrolled patients, 65 patients received TKI treatment alone (TKI arm) and 68 patients received dual treatment of upfront stereotactic radiotherapy to all sites of disease along with first-line TKI treatment (dual treatment arm). The median follow-up time was 19.6 months (interquartile range, 9.4-41.0 months).

The median PFS for the TKI arm versus the dual treatment arm was 12.5 months and 20.2 months, respectively (hazard ratio [HR], 0.6188; 95% confidence interval [CI], 0.3949-0.9697; log-rank P <.001). The median OS for the TKI arm versus the dual treatment arm was 17.4 months and 25.5 months, respectively (HR, 0.6824; 95% CI, 0.4654-1.001; log-rank P <.001). Grade 3/4 adverse events included pneumonitis (7.3% with dual treatment vs 2.9% in the TKI arm; P >.05) and esophagitis (4.4% with dual treatment vs 3.0% in the TKI arm; P >.05). No grade 5 adverse events or deaths resulted from treatment.

Dual treatment of upfront stereotactic radiotherapy to all sites of disease along with first-line TKI improved PFS and OS compared with first-line TKI treatment alone. The authors concluded that aggressive local therapy should be further studied in larger phase 3 trials as a potential standard treatment option in previously untreated EGFRm oligometastatic NSCLC.

Reference
Wang XS, Zeng M. J Clin Oncol. 2020;38(suppl 15):Abstract 9508.