Future directions in the treatment of patients with EGFR mutated advanced NSCLC
Clinical trials using combinatorial approaches that have shown positive results are described below.
In an ongoing phase I/II study in patients withmetastatic EGFR-mutated (L858R or del19) NSCLC, 27 patients were given osimertinib plus gefitinib for treatment naïve patients[46]. The maximum tolerated dose was 80 mg osimertinib plus 250 mg gefitinib orally daily. 81.5% patients were able to complete≥ six cycles combination therapy (1 was discontinued for progressive disease, 4 for side-effects) with ORR of 85.2% (95% CI, 67.5%-94.1%).Nearly 82.4% of treated patients were found to have undetectable plasma EGFR at 2 weeks of treatment. The median progression- free survival was not reached (NR) at 14.8 months follow up [46].
In the phase II portion of a single-center phase I/II trial, the combination of first-line osimertinib plus bevacizumabresulted in a significantly improved 1-year PFS of76%as compared to historical rate of 51%[47].
In NEJ026, a phase III trial comparing bevacizumab plus erlotinib to monotherapy with erlotinibfor EGFR-mutated NSCLC, the combination regimen was associated with significantly superior PFS compared to single agent erlotinib[48]. At the time of interim analysis (12.4 months), patients in the erlotinib plus bevacizumab group had significantly better median PFS of 16.9 months (95% CI, 14.2-21.0) compared with 13.3 months (95% CI, 11.1-15.3) for patients in the erlotinib group (HR 0.605; 95% CI, 0.417-0.877; p=0.016)[48].Updated results of this trial presented at ASCO 2020 showed median OS with bevacizumab plus erlotinibof 50.7 months (95% CI, 37.3-NR) compared to 46.2 months (95% CI, 38.2-NR) with erlotinib alone (HR, 1.00; 95% CI, 0.68-1.48). Bevacizumab plus erlotinib were also found to have higher median survival time between enrollment and progression of disease with second line treatment ( 28.6 months compared to 24.3 months ) with erlotinib alone
[49].