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.