First-Line Sunvozertinib in NSCLC with EGFR Exon 20 Insertion Mutations

Area of Science:

• Oncology
• Clinical Trials
• Pharmacology

Background:

• Sunvozertinib is approved for later-line treatment of advanced non-small-cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) exon 20 insertion mutations.
• Efficacy and safety data for sunvozertinib as a first-line treatment for NSCLC are limited.

Purpose of the Study:

• To evaluate the efficacy and safety of sunvozertinib compared to chemotherapy as a first-line treatment for advanced NSCLC patients with EGFR exon 20 insertion mutations.

Main Methods:

• A Phase 3, international, randomized trial comparing sunvozertinib to chemotherapy (carboplatin-pemetrexed) in 324 patients with advanced nonsquamous NSCLC and EGFR exon 20 insertions.
• Primary endpoint: progression-free survival (PFS) by blinded independent central review.
• Secondary endpoints included overall survival, investigator-assessed PFS, objective response rate, and safety.

Main Results:

• Sunvozertinib demonstrated significantly longer median PFS (10.3 months) versus chemotherapy (7.5 months) (HR, 0.65; P<0.001).
• Objective response rate was higher with sunvozertinib (58.9%) compared to chemotherapy (31.1%).
• Grade 3 or higher adverse events were more frequent with sunvozertinib (75.5%) than chemotherapy (56.7%), with increased serum creatine kinase, diarrhea, and anemia being most common.

Conclusions:

• Sunvozertinib shows superior efficacy compared to chemotherapy as a first-line treatment for advanced NSCLC with EGFR exon 20 insertion mutations.