Abstract
BACKGROUND: For patients with metastatic lung adenocarcinoma, systemic therapy with platinum-based chemotherapy associated with immunotherapy is the standard of care. The treatment decision seems to be more difficult with a second cancer occurrence during the treatment course. Here we report a rare case of concomitant urothelial and lung adenocarcinoma in which both tumors responded to enfortumab vedotin, an antibody-drug conjugate targeting nectin-4-a response not previously described in this setting. CASE PRESENTATION: We describe a 74-year-old white male who was diagnosed with metastatic lung adenocarcinoma (KRAS G12C mutation, PD-L1 5%) and developed locally advanced urothelial carcinoma during first-line treatment for lung cancer. The second urothelial nodal recurrence following platinum-based chemotherapy leads to enfortumab vedotin initiation. Enfortumab vedotin, an antibody-drug conjugate, was initiated under early access authorization and produced a complete response of urothelial lesions and partial response of lung lesions. Treatment was discontinued after 16 months due to grade 2 neuropathy and persistent complete response. CONCLUSION: This exceptional case demonstrates a prolonged dual response of urothelial and lung adenocarcinomas to enfortumab vedotin. It highlights the potential role of nectin-4-targeted therapy beyond urothelial carcinoma and supports further investigation of this agent in non-small cell lung cancer.