EGFR and MET Combined Inhibition in EGFR-Mutated Advanced NSCLC: A Real-World Study

Resistance to EGFR tyrosine kinase inhibitors (TKIs) often occurs through the mechanism of MET amplification. No consensus exists on the standard treatment strategy for patients with MET amplification due to the lack of trial-derived clinical data. Three regimens commonly administered to patients with MET amplification–mediated EGFR-TKI progression are EGFR-TKI and MET-TKI combination therapy, MET-TKI monotherapy, or chemotherapy. Researchers presented data comparing the effectiveness of these regimens at ASCO 2021.¹

Patients with EGFR-mutated advanced NSCLC who progressed from prior EGFR-TKI through the acquisition of MET amplification and received treatment were included in this study (n = 70).¹ Of the 70 patients, 38 received EGFR-TKI plus crizotinib, 10 received crizotinib monotherapy, and 22 received platinum-based doublet chemotherapy.¹ Somatic mutation profiling was performed on blood and tissue biopsy samples, and resistance mechanisms to the combination targeted therapy were also explored in 12 patients.¹

The objective response rate (ORR) and disease control rate (DCR) were 48.6% and 82.9% for the EGFR-TKI + crizotinib group, 40% and 70% for the crizotinib monotherapy group, and 18.2% and 50% in the chemotherapy group.¹ The EGFR-TKI + crizotinib group had significantly better ORR (P = .026) and DCR (P = .016) compared with the chemotherapy group, but these efficacy data were not statistically different from the crizotinib monotherapy group (ORR, P = .73; DCR, P = .39).¹ Progression-free survival (PFS) was significantly longer for the EGFR-TKI + crizotinib group than those who received crizotinib monotherapy (5.0 vs 2.3 months; P = .004) or chemotherapy (5.0 vs 2.9 months; P = .036), but overall survival was similar (10.0 vs 4.1 vs 8.5 months; P = .088).¹

Two common concurrent mutations in the 3 cohorts were TP53 mutations (58.5%) and EGFR amplifications (42.9%).¹ PFS was significantly longer for patients who received EGFR-TKI + crizotinib and had either a concurrent TP53 mutation (n = 17) (6.0 vs 2.3 vs 2.9 months; P = .0091) or concurrent EGFR amplification (n = 13) (5.0 vs 1.2 vs 2.4 months; P = .016).¹

This cohort provides the largest real-world clinical evidence to date that demonstrates simultaneous inhibition of EGFR and MET improves clinical outcomes of patients with EGFR-mutated NSCLC who acquired MET amplification from prior EGFR-TKI therapy, indicating that the combination regimen of EGFR-TKI and MET-TKI could be more effective in this patient subset.¹

Reference

1. Li L, Qu J, Heng J, et al. A large real-world study on the effectiveness of the combined inhibition of EGFR and MET in EGFR-mutant advanced non-small cell lung cancer (NSCLC). American Society of Clinical Oncology (ASCO), June 2021; Abstract 9043.