Advanced lung adenocarcinoma patient with EGFR exon 20 insertion benefits from high-dose furmonertinib for nine months after progression from mobocertinib: a case report

Background: The treatment landscape of non-small cell lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR) mutation has significantly changed in the past decade. However, EGFR exon 20 insertion (20ins), which accounts for at least 9% of all EGFR mutated cases, has been generally associated with resistance to common EGFR tyrosine kinase inhibitors (TKIs). In recent years, major progress has been made in the precision treatment of NSCLC harboring EGFR exon 20ins, thanks to the development of TKIs and mAb-based agents specifically targeting EGFR 20ins. However, the efficacy of these novel agents, such as mobocertinib and amivantamab, is not quite satisfactory. Therefore, there is an urgent need to identify other effective targeted drugs. Case Description: Herein, we describe a case with EGFR 20ins diagnosed by amplification refractory mutation system polymerase chain reaction (ARMS-PCR) who benefited from high-dose (160 mg/d comparing with Phase II recommended dose 80 mg/d) furmonertinib, a novel third-generation EGFR TKI, after progression from mobocertinib. A 58-year-old male was referred to our clinic with multiple lung lesions detected in computed tomography (CT) scanning. The patient participated in a phase I/II trial (NCT02716116) receiving TAK-788 and was confirmed with partial response at follow-up. Intriguingly, after progression from 9 months of TAK-788 treatment, the patient still showed response to furmonertinib. The progression free survival was 10 months with no complications or adverse events observed. The overall survival was 34 months till last follow-up in March, 2022. The patient is still in follow-up. Conclusions: Supported by this case and data from other studies, the potency of furmonertinib warrants further evaluation in patients with EGFR 20ins, especially those pretreated with TKIs.