Pathological complete response and long-term survival by pembrolizumab based immunochemotherapy in epidermal growth factor receptor mutated non-small cell lung cancer post-tyrosine kinase inhibitor failure: a case report and tumor microenvironment analysis.

Abstract

Background: Lung adenocarcinoma harboring epidermal growth factor receptor (EGFR) mutations remains a significant clinical challenge, particularly when patients experience progression following EGFR-tyrosine kinase inhibitor (TKI) therapy. This case report explores the efficacy of pembrolizumab-based immunochemotherapy (ICT) in achieving a pathological complete response (pCR) and prolonged survival in a patient with EGFR-mutated non-small cell lung cancer (NSCLC) after TKI failure.

Case description: A 74-year-old female patient with stage IVa EGFR L858R-mutated lung adenocarcinoma, progressing under multiple lines of EGFR-TKI therapy, was treated with pembrolizumab in combination with pemetrexed and carboplatin. Tumor response was assessed using radiological imaging and positron emission tomography-computed tomography (PET-CT). Pathological evaluation was conducted post-surgery, and the tumor microenvironment (TME) was analyzed using multiplex immunofluorescence (mIF) staining. Following four cycles of pembrolizumab-based ICT, the patient exhibited a significant reduction in tumor burden and mediastinal lymph node involvement, as confirmed by PET-CT. Surgical resection revealed a pCR with no viable tumor cells existed. The microenvironment analysis for tumor samples obtained post-progression on targeted therapy demonstrated that more than 50% of tumor cells expressing programmed cell death 1 ligand 1 (PD-L1), accompanying with higher infiltration of programmed death receptor 1 (PD-1)⁺ CD8⁺ T cells and PD-L1⁺ CD68⁺ macrophages in the tumor area compared to the stromal area. As for resected samples, substantial infiltration of CD45⁺ immune cells, CD8⁺ T lymphocytes, CD68⁺ macrophages and immature tertiary lymphoid structures (TLSs) were detected.

Conclusions: This case report highlights the potential of pembrolizumab-based ICT to induce a pCR and achieve long-term survival in EGFR-mutated NSCLC patients post-TKI failure. The favorable TME observed supports the rationale for this therapeutic approach and warrants further investigation in prospective clinical trials.