Immune checkpoint inhibitors in EGFR-mutation positive TKI-treated patients with advanced non-small-cell lung cancer network meta-analysis

Abstract

Non-Small Cell Lung Cancer (NSCLC) patients with Epidermal Growth Factor Receptor (EGFR) mutation benefit from a first line of treatment with tyrosine kinase inhibitors (TKIs). After progression, the choice of treatment is between chemotherapy and immune checkpoint inhibitors, but the role of EGFR mutation in the response to immunotherapy is still unclear. A network meta-analysis was performed and 4 randomized trials comparing immune checkpoint inhibitors versus chemotherapy were identified. A Bayesian network meta-analysis was carried out to compare three checkpoint inhibitors (nivolumab, pembrolizumab and atezolizumab) versus chemotherapy (docetaxel), evaluating their Hazard Ratio (HR) and 95% Confidence Interval (CI) for Overall Survival (OS). Results suggest that patients with NSCLC and EGFR mutation, previously treated with TKIs, show better OS when treated with docetaxel in comparison to checkpoint inhibitors treatment.

Predictive Value of Soluble PD-1, PD-L1, VEGFA, CD40 Ligand and CD44 for Nivolumab Therapy in Advanced Non-Small Cell Lung Cancer: A Case-Control Study

“…We subsequently investigated this biomarker in a cohort of 36 EGFR-mutated patients. Previous studies have reported that EGFR-mutated NSCLC patients are poor responders to nivolumab [13,41]. All 36 patients exhibited baseline sCombo positivity due to a constant expression of sPD-L1, thus, these results suggest that baseline sCombo positivity may not only be prognosic, but most importantly could be predictive of failure of nivolumab therapy in NSCLC patients.…”

“…In our control cohort of 36 NSCLC EGFR-mutated patients, all patients exhibited a constant baseline expression of sPD-L1. Given that EGFR-mutated lung cancers are known to be resistant to anti-PD1 therapies [41,56], these findings support a deleterious effect of sPD-L1 expression on nivolumab efficacy in NSCLC patients. Interestingly, in a previous study a similar trend has been observed among NSCLC patients treated with another anti-PD1, pembrolizumab combined with low doses of chemotherapy.…”

“…It was considered to be the best choice given that most patients with EGFR wild-type NSCLC would receive anti-PD1 therapy during the course of their diseases. Additionally, EGFR mutation is known to be associated with resistance to immunotherapy, therefore evaluating biomarkers in these patients is of particular interest [41]. Interestingly, studies have shown that EGFR-mutated NSCLC tended to express PD-L1 on tumor cells at higher frequency, yet they benefit less from anti-PD1 therapies than wild-type tumors [13,58,59].…”

“…Overall, 87 patients were included, with 51 patients in nivolumab group and 36 patients in control EGFR-mutated group. EGFR-mutated patients were younger (median age 45 (35)(36)(37)(38)(39)(40)(41)(42)(43)(44)(45)(46)(47)(48)(49)(50)(51) vs. 66 (60-69) years old, p < 0.001). More than 95% of patients had an ECOG performance status of 2 or less in both groups.…”

<p>A Comprehensive Review of Contemporary Literature for Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors in Non-Small Cell Lung Cancer and Their Toxicity</p>

“…87 Checkpoint inhibitor therapy is generally ineffective in this patient population. 88,89 Enrollment in clinical trials is ideal and should be strongly considered for these patients.…”