Abstract
BackgroundData on the use of immune checkpoint inhibitors (ICIs) in advanced non-small cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR) mutation are limited. The current study aimed to assess the efficacy of ICIs in EGFR-mutant advanced NSCLC and explore the relevant influential factors.Materials and MethodsRelevant clinical data of EGFR-mutant NSCLC patients who had received ICIs were collected from multiple hospitals. The primary endpoint was progression-free survival (PFS), and the secondary endpoints were overall survival (OS), objective response rate (ORR), and relevant influential factors.ResultsA total of 122 advanced EGFR-mutant NSCLC patients were included in the final analysis. The total cohort had an objective response rate (ORR) of 32.0%, a median progression-free survival (mPFS) of 5.0 months, and a median overall survival (mOS) of 14.4 months. Among 96 patients with common EGFR mutations (19Del, 52 patients; L858R, 44 patients), those who were administered front-line ICI exhibited better survival benefits than those who received later-line ICI after disease progression on tyrosine kinase inhibitors (TKIs) treatment (mPFS: 7.2 months vs. 3.4 months, respectively, P < 0.0001; mOS: 15.1 months vs. 8.4 months, respectively, P <0.0001). Moreover, the efficacy of ICI-based combination therapy was better than that of ICI monotherapy (mPFS: 5.0 months vs. 2.2 months, respectively, P = 0.002; mOS: 14.4 months vs. 7.0 months, respectively, P = 0.001). Multivariate analysis showed that ICI-based combination therapy and front-line ICI administration after progression on EGFR-TKI were associated with significant improvements in both PFS and OS (P < 0.05). A high PD-L1 expression (tumor proportion score, TPS≥50%) and the EGFR L858R mutation were only significantly associated with a better PFS (P <0.05). A better Eastern Cooperative Oncology Group (ECOG) status was independently associated with a favorable OS (P <0.05).ConclusionsTaken together, combination immunotherapy in front-line was associated with improvement of survival in EGFR-mutant NSCLC patients post-TKI resistance. Further prospective studies with large sample sizes are required to identify the optimal combinatorial treatment strategy.
Highlights
Epidermal growth factor receptor tyrosine kinase inhibitors (EGFRTKIs) as a standard first-line treatment for advanced non-small-cell lung cancer harboring epidermal growth factor receptor (EGFR) mutation yield great efficacy but acquired resistance and disease progression are inevitable [1,2,3]
EGFR mutation subtypes consisted of EGFR exon 19 deletion (19Del) (N = 52, 42.6%), EGFR exon 21 EGFR exon L858R mutation (L858R) mutation (EGFR 21 L858R) (N = 44, 36.1%), EGFR EGFR Exon 20 insertion (20Ins) (N = 23, 18.9%), and three other patients had uncommon mutations (G719X, N = 2; L861Q, N = 1). 69 of patients carrying EGFR common mutation (19Del, 21 L858R) underwent gene re-test after first or second-generation TKI treatment, with 31 cases acquired T790M mutation. 43 cases with common EGFR mutation were treated with osimertinib after progression on first and second-generation TKI
The results indicated that strongly positive programmed cell death-ligand 1 (PD-L1) expression (TPS≥50%), ICIbased combination therapy, front-line immune checkpoint inhibitors (ICI) treatment after EGFR TKI progression, and the EGFR L858R genotype were all significantly associated with improved progressionfree survival (PFS) (P
Summary
Epidermal growth factor receptor tyrosine kinase inhibitors (EGFRTKIs) as a standard first-line treatment for advanced non-small-cell lung cancer harboring EGFR mutation yield great efficacy but acquired resistance and disease progression are inevitable [1,2,3]. Subgroup analysis in the IMpower 150 study showed that the combination of paclitaxel, carboplatin, bevacizumab, and atezolizumab improved PFS but not significant OS benefit as compared to that with bevacizumab plus chemotherapy. This four-drug regimen owned an incidence of grade 3 to 4 treatment-related adverse events of 57% [16]. Data on the use of immune checkpoint inhibitors (ICIs) in advanced nonsmall cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR) mutation are limited. The current study aimed to assess the efficacy of ICIs in EGFRmutant advanced NSCLC and explore the relevant influential factors
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