Multicenter phase 2b trial of sutetinib for non-small cell lung cancer harboring uncommon EGFR mutations

Uncommon EGFR mutations account for approximately 10% of EGFR-altered non-small cell lung cancer (NSCLC) and show heterogeneous sensitivity to EGFR-TKIs, with limited prospective evidence to inform first-line therapy. Sutetinib is an irreversible EGFR-TKI. A multicenter phase 2b trial in China evaluated sutinib in adult patients with locally advanced or metastatic NSCLC with uncommon EGFR mutations who had no prior EGFR-TKI therapy. The trial included 99 patients harboring EGFR G719X, S768I, L861Q or predefined compound mutations. The patients received oral sutetinib 80 mg once daily until radiographic progression or unacceptable toxicity. The primary endpoint was objective response rate (ORR), as assessed by an independent review committee (IRC). The median follow-up was 16.6 months. Ammong efficacy-evaluable patients (n=96), the IRC-ORR was 70.8% (95% CI 60.7-79.7) and the disease control rate was 90.6% (82.9-95.6); median duration of response was 12.0 months (9.3-15.7); median progression-free survival was 13.7 months (10.9-16.4); and median overall survival was not reached (22.2 months- not reached). ORR was numerically higher in patients with compound versus solitary uncommon EGFR mutations (84.4% versus 64.1%), with median PFS of 13.8 versus 11.0 months. Treatment-related adverse events of any grade occurred in 97.0% of patients, and grade 3-4 TRAEs occurred in 42.4%. TRAEs led to dose reduction in 34.4% and to discontinuation in 4.0%. No treatment-related deaths occurred. The authors conclude that sutetinib demonstrated clinically meaningful antitumor activity with manageable safety in advanced NSCLC harboring uncommon EGFR mutations.