Case Report: Dramatic response to amivantamab plus chemotherapy in EGFR G719A-mutant lung adenocarcinoma with liver and peritoneal metastases.

Background: Hepatic metastasis and uncommon mutations are recognized risk factors in patients with epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer. The phase 3 MARIPOSA-2 trial demonstrated superior outcomes with amivantamab plus chemotherapy compared to chemotherapy alone in patients whose disease progressed during EGFR-tyrosine kinase inhibitor therapy. However, its efficacy and tolerability in patients with hepatic metastases or uncommon EGFR mutations remain unclear. Case description: A 52-year-old male smoker was diagnosed with stage IVB lung adenocarcinoma harboring an uncommon EGFR G719A mutation. He received afatinib as first-line therapy, followed by pemetrexed/carboplatin and later a quadruple regimen of atezolizumab, bevacizumab, paclitaxel, and carboplatin. Despite these treatments, disease progression occurred, presenting as multiple hepatic metastases, massive ascites, and new brain lesions, resulting in declining performance status. A combination of amivantamab, pemetrexed, and carboplatin was initiated as fourth-line salvage therapy. Results: Follow-up imaging showed marked regression of the lung mass, hepatic and brain metastases, and resolution of ascites, suggesting a near-complete response. His performance status gradually improved, and the response has remained durable for over nine months with manageable grade 1-2 skin rash and stomatitis. Conclusion: This case is the first to demonstrate a durable, near-complete response to amivantamab combined with chemotherapy in a patient harboring an uncommon EGFR G719A mutation and extensive visceral metastases. Although further studies are warranted, this report highlights amivantamab-based combination therapy as a promising salvage option for high-risk patients.