Abstract
BACKGROUND: Metastatic non-small-cell lung cancer (NSCLC) represents a significant clinical challenge and is the leading cause of cancer-related death worldwide. Immune checkpoint inhibitors (ICIs), particularly those targeting the programmed cell death protein 1 (PD-1)/programmed cell death-ligand 1 (PD-L1) pathway, have transformed the treatment of advanced-stage NSCLC; however, their efficacy varies, and optimal strategies following initial ICI failure remain undefined. Envafolimab, a novel humanized single-domain anti-PD-L1 antibody fragment fused to an Fc domain, is the first globally approved subcutaneous PD-L1 inhibitor. Its unique structure confers advantages in terms of tissue penetration and distribution compared to conventional monoclonal antibodies. CASE DESCRIPTION: This report details the case of a 66-year-old male diagnosed with stage IVB (cT4N2M1c) squamous cell carcinoma of the left upper lung with confirmed hepatic metastasis. Initial immunohistochemistry revealed a tumor proportion score for PD-L1 ≥1%, prompting the following standard first-line therapy as per the guidelines: three cycles of albumin-bound paclitaxel [470 mg, day (d)1], carboplatin (568 mg, d1), and pembrolizumab (200 mg, d1). This regimen yielded inadequate disease control. Subsequently, second-line therapy comprising two cycles of gemcitabine (1.6 g, d1; 1.4 g, d8), cisplatin (40 mg, d1-3), endostar (30 mg, d1-4), and subcutaneous envafolimab (200 mg, d1) was initiated. Follow-up computed tomography (CT) imaging revealed a notable reduction in the left hilar mass and significant alleviation of the bronchial obstruction. This therapeutic response was sustained for over 6 months during envafolimab monotherapy maintenance without recurrence. CONCLUSIONS: This case shows the potential efficacy of envafolimab-based combination therapy in achieving a clinically significant and durable response for a patient with metastatic squamous NSCLC (sq-NSCLC) who showed disease progression on first-line pembrolizumab-containing chemotherapy. It suggests that envafolimab warrants consideration as a viable treatment option in this setting, particularly following the failure of PD-1 inhibitors. Further larger clinical trials need to be conducted to confirm these findings and define its optimal role in the NSCLC treatment sequence.