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].