The good news
The U.S. Food and Drug Administration (FDA) has granted accelerated approval to sunvozertinib for the treatment of adult patients with advanced or metastatic non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) exon 20 insertion mutations, whose disease has progressed on or after platinum-based chemotherapy.
Why it’s important
EGFR mutations are present in 15-20% of NSCLC. These mutations are drivers of cancer development and have been successfully targeted with tyrosine kinase inhibitors (TKIs) that reduce cancer growth and improve patient survival. Not all EGFR mutations are created equally. The most common EGFR mutations are in exons 19 and 21 and they are the most responsive to treatment with the EGFR-TKIs. EGFR exon 20 insertion mutations represent about 10% of all EGFR mutations. The agents available for the treatment of the more common EGFR mutant lung cancers have not been as successful in most of the lung cancers that harbor an EFGR mutation. The current first-line treatment of advanced EGFR exon 20 insertion mutant lung cancer is amivantamab (an antibody that binds to both EGFR and MET) combined with chemotherapy. There are no approved treatments after the initial therapy fails.
Sunvozertinib is an oral TKI that specifically targets the EGFR exon 20 insertion mutation. In the WU-KONG1B (NCT03974022) clinical trial 85 patients with previously treated, metastatic NSCLC containing EGFR exon 20 insertion mutations were given sunvozertinib. Nearly half of the patients (46%) had significant shrinkage of their cancer, and the response lasted for nearly a year for many of the patients. The side effects included gastrointestinal toxicities (diarrhea, constipation, nausea, vomiting), skin rash and dryness, mouth sores, eye problems, fatigue, and pneumonitis (inflammation of the lungs).
What it means for patients
NSCLC with EGFR exon 20 insertion mutations have been difficult to treat because they do not respond well to the EGFR TKIs used for lung cancers containing the more common EGFR mutations. The FDA approval of sunvozertinib represents some progress in the treatment of this subtype of NSCLC.
What to look for
There will likely be more trials evaluating sunvozertinib in combination with other agents or possibly as initial therapy for patients with advanced NSCLC who have EGFR exon 20 insertion mutations. Expect that the development of novel drugs for this particular type of lung cancer will continue.