Epidermal growth factor receptor (EGFR) mutations are common driver genes in nonsmall-cell lung cancer and have different sensitivities to EGFR-tyrosine kinase inhibitors (EGFR-TKIs). EGFR is divided into classic mutations and rare mutations. Classic mutations are well known, but the understanding of rare mutations is not sufficient. In this article, we summarize the clinical research and treatment progress of rare mutations for different EGFR-TKIs and provide a basis for clinical treatment decisions.

Background Epidermal growth factor receptor-tyrosine kinase inhibitors ( EGFR -TKIs) play a dominant role in the treatment of non-small cell lung cancer (NSCLC); however, to date, targeted treatment options have not been identified for patients with EGFR exon 20 insertion (ex20ins) mutations. Almonertinib, as the third generation EGFR -TKI, can irreversibly bind to EGFR ATP binding region and has a favorable therapeutic effect in EGFR + multiple targets inhibition. Almonertinib is suitable for the treatment of NSCLC patients with disease progression and T790M drug resistance mutation positive after other EGFR -TKI treatment. Case Description We report the case of a female patient with NSCLC with an EGFR ex20ins mutation (p.Ala767_Val769dup) identified by next-generation sequencing (NGS). The patient received systemic chemotherapy after surgical resection of the lesion. After the progression of first-line chemotherapy, the patient received sequential targeted therapy with afatinib and poziotinib, achieving progression-free survival (PFS) of 3.2 and 10.4 months, respectively. After the progression, we chose almonertinib when the patient refused to re-chemotherapy. Under the treatment of almonertinib, the PFS time of the patient reached 14 months. Conclusions Almonertinib had the most substantial effect, and its use has not been previously reported for NSCLC patients with EGFR ex20ins mutations. The successful application of almonertinib reported here indicates that is a potential new treatment regimen for patients with EGFR ex20ins mutations.