New resistance mechanisms continue to be identified
One of the most common sets of resistance mutations are insertions in exon 20 of the EGF receptor gene. These are a heterogenous group of mutations, many of which do not respond to first-, second-, or third-generation TKIs. Some, such as EGFR-A763_Y764insFQEA, may be sensitive to first- and third-generation EGFR TKIs. Other drugs targeting exon 20 insertion mutations are under development.
Newly approved by the FDA within the last year are mobocertinib and CLN-081 for adult patients with locally advanced or metastatic NSCLC with EGFR exon 20 insertion mutations.
Savolitinib is a receptor tyrosine kinase (MET) inhibitor currently under development for NSCLC and other cancers. Amivantamab-vmjw was approved by the FDA last year for metastatic NSCLC. It targets EGF and MET receptors in patients with EGFR exon 20 insertion mutations.
We finally have approved drugs for exon 20 insertions and c-Met amplification, even though their approvals are based on small, single arm studies with no definitive claims of improved efficacy over older therapies. as in my patient described in this article.
Dr. Schiller is a medical oncologist and founding member of Oncologists United for Climate and Health. She is a former board member of the International Association for the Study of Lung Cancer and a current board member of the Lung Cancer Research Foundation.