Brain Metastatic Tumor Flare After Sunvozertinib Dose Reduction in a Patient with Surgical Resected EGFR ex20ins NSCLC.

Therapeutic options for NSCLC with epidermal growth factor receptor exon20 insertions (EGFR ex20ins) are limited. Sunvozertinib is a novel orally EGFR inhibitor that has been approved to treat EGFR ex20ins NSCLC at second line setting. Herein, we reported an unexpected therapeutic outcome of first-line sunvozertinib treatment in a patient with stage IIIB EGFR ex20ins-positive lung adenocarcinoma (T1cN3M0). We found three months of sunvozertinib neoadjuvant treatment led to remarkable shrinkage of the primary tumor and downstaged N3 metastatic disease. A radical resection was scheduled after careful evaluation. Histological assessment of the resected tumor and lymph nodes showed a complete pathologic response. The patient was recommended to continue sunvozertinib as an adjuvant therapy, whereas he developed brain metastasis within three months after surgery. We proposed that the brain metastasis occurred as a result of sunvozertinib dose de-escalation-induced disease flare. Rechallenge with adequate dosage of sunvozertinib led to a rapid shrinkage of the brain metastasis. Our case highlighted the feasibility of sunvozertinib neoadjuvant therapy in EGFR ex20ins-positive NSCLC patient with locally advanced disease. Importantly, adjuvant therapy using an adequate dosage of sunvozertinib is pivotal to prevent disease flare and tumor recurrence.