A meta-analysis comparing therapeutic outcomes for anti-EGFR monotherapy to targeted therapy combinations for non-small cell lung cancer.

Abstract

e21570 Background: Small molecule inhibitors of epidermal growth factor receptor kinase (EGFR) are approved for EGFR-positive non-small cell lung cancer (NSCLC). Targeted therapies include agents that block tumor-specific molecular targets and thereby interfere with tumor growth and metastasis. This study focuses on a meta-analysis of therapeutic outcomes from phase II and III clinical trials for anti-EGFR monotherapy compared to anti-EGFR therapy in combination with targeted agents. Methods: A literature search was conducted using EMBASE, Pubmed, Scifinder Scholar, clinicaltrials.gov and the Cochrane library for the following terms: “epidermal growth factor receptor kinase”, “combination therapy”, “non-small cell lung cancer”. Eligible studies included patients of advanced stage IV NSCLC and any mutation status that met the predefined inclusion criteria. Data was extracted on trial demographics and therapeutic outcomes including progression-free survival (PFS), survival post progression (SPP), overall survival (OS) and adverse events (AE). Sub-group analysis based on patient mutation status of wild-type (wt) EGFR, mutant EGFR, wt KRAS and mutant KRAS and a correlation analysis between OS, PFS and SPP was conducted. Results: A total of 34 studies were identified that fit the inclusion criteria from 2009-2019. The pooled OS hazard ratio (HR) was 0.94 (95% Confidence Interval (CI): 0.87-1.01); the pooled PFS HR was 0.8 (95% CI: 0.74-0.87). Median OS correlated more closely with median SPP (r2 = 0.97 for monotherapy; r2 = 0.88 for combination therapy) than to median PFS (r2 = 0.90 for monotherapy; r2 = 0.82 for combination therapy), although the linear association between log-HR OS and log-HR PFS had a positive slope (β = 0.31± 0.19). A greater incidence of rash and diarrhea was observed in the combination arm compared to monotherapy. A significant improvement was observed for PFS in wt EGFR patients for combination therapy, pooled PFS HR 0.8 (95% CI: 0.67-0.95). Conclusions: A statistically significant improvement in PFS was observed for anti-EGFR combination regimens compared to anti-EGFR monotherapy. The improvement in OS was not statistically significant for anti-EGFR combination regimens compared to monotherapy.