Abstract
ObjectivesMore and more encouraging evidence revealed that immunotherapy could improve clinical outcomes in patients with previously treated non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) variations. However, immunotherapy is still a controversy for NSCLC patients with EGFR mutation.MethodIn this retrospective analysis, we compared the clinical efficacy of pembrolizumab monotherapy (PM), pembrolizumab combined with chemotherapy (P+C) and pembrolizumab combined with anlotinib (P+A) in NSCLC patients with EGFR mutation who had failed on EGFR-TKI and platinum-based chemotherapy.ResultEighty-six patients were included in this study. The overall median progression free survival (PFS) was 3.24 months. Multivariate analysis suggested that EGFRL858R and combined therapy were positive prognostic factors of PFS. The overall median OS was 12.28 months. Multivariate analysis found that high PD-L1 expression (≥50%) and combined therapy seemed to be positive prognostic factors of OS. Among the population, 32 patients received PM, 26 patients received P+C and 28 patients received P+A. Up to Jan 30, 2021, the median progression-free survival was 1.5 months in the PM group, 4.30 months in the P+C group and 3.24 months in the P+A group. The median OS were 7.41, 14.92 and 15.97 months, respectively. The ORR were 3.1%, 23.1% and 21.4%.ConclusionThe addition of chemotherapy or antiangiogenic therapy to pembrolizumab resulted in significantly longer PFS, OS and ORR than pembrolizumab alone in our study. EGFRL858R might be a positive prognostic factor of PFS and high PD-L1 expression might be a positive prognostic factor of OS.
Highlights
Targeted therapy has revolutionized the treatment landscape for patients with non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) mutations
Eighty-six patients met the following inclusion criteria: [1] stage IV NSCLC [2] positive EGFR mutation [exon 19 deletion mutation (EGFRD19), exon 21 L858R mutation (EGFRL858R), secondary exon 20 T790M mutation and other uncommon sensitive mutation such as G719X, L861R] [3] patients had disease progressed with at least 1 approved EGFR-TKI and platinum-based chemotherapy following standard treatment guideline; [4] patients received pembrolizumab monotherapy (PM), pembrolizumab combined with chemotherapy (P+C) or pembrolizumab combined with anlotinib (P+A) [5] Eastern Cooperative Oncology Group performance status (ECOG PS) 0-1
The most common EGFR mutation type was EGFRL858R (54.6%), followed by EGFRD19 (25.6%), uncommon sensitive mutation (10.5%) and T790M (9.3%). 75 patients were screened for Programmed Death Ligand 1 (PD-L1) expression levels immediately before immunotherapy, 17 (19.8%) of whom had a Tumor Proportion Score (TPS) of 0%, 32 (37.2%) of whom had a TPS of 1-49% and 26 (30.2%) of whom had a TPS of 50% or greater
Summary
Targeted therapy has revolutionized the treatment landscape for patients with non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) mutations. Treatment with EGFR-TKIs, which have been developed to the third generation, provides better disease control and longer survival for patients with EGFR mutations [1]. Several studies have revealed that high PD-L1 expression predicted poor response to EGFR-TKIs in patients with EGFR-mutant NSCLC and correlated with primary resistance to EGFR-TKIs [8,9,10]. EGFR-TKIs have shown overwhelming advantages over standard chemotherapy in patients with EGFR-mutant NSCLC. EGFR-TKIs are recommended as the first-line treatment in this population according to the NCCN guidelines. Treatment options after the development of TKI resistance need to be further explored. Given the growing emphasis on molecular profiling and detection of PD-L1, more detailed treatment guidance is needed for the critical population of patients with advanced NSCLC with both high PD-L1 and EGFR mutations
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