No extra PFS benefit with bevacizumab plus osimertinib in EGFR-mutated NSCLC
medwireNews: Adding bevacizumab to osimertinib therapy does not improve progression-free survival (PFS) for patients with advanced non-small-cell lung cancer (NSCLC) harboring an EGFR T790M mutation, phase 2 study data suggest.
Although the combination was tolerable, the efficacy findings did not confirm those of recent single-arm trials, report Hiroaki Akamatsu (Wakayama Medical University, Japan) and co-authors in JAMA Oncology.
Akamatsu and team found that median PFS was 9.4 months among the 41 people (mean age 68 years, 40% men) randomly assigned to receive oral osimertinib 80 mg/day plus intravenous bevacizumab 15 mg/kg every 3 weeks as part of the West Japan Oncology Group 8715L trial.
This did not significantly differ to the median PFS of 13.5 months among the 40 individuals (mean age 70 years, 41% men) given osimertinib monotherapy.
All participants had advanced stage IIIb–IV or recurrent NSCLC that had progressed during prior EGFR–tyrosine kinase inhibitor treatment and had acquired an EGFR T790M mutation.
Despite there being no significant difference in PFS, the researchers note that the overall response rate was significantly higher with osimertinib plus bevacizumab than osimertinib monotherapy, at 71.8% versus 55.0%.
Conversely, there was no significant difference in median time to treatment failure (8.4 vs 11.2 months) or median overall survival (not reached vs 22.1 months) between the combination and monotherapy arms.
Subgroup analyses suggested that patients given osimertinib plus bevacizumab had significantly shorter PFS when they had a history of vascular endothelial growth factor (VEGF) inhibitor use relative to no previous anti-VEGF use (4.6 vs 11.1 months).
By contrast, there was no significant difference in PFS between those with versus without prior anti-VEGF exposure in the osimertinib monotherapy arm (15.1 vs 13.7 months).
Given these findings, Akamatsu and co-investigators say that the “efficacy of osimertinib plus anti-VEGF therapy should be explored as first-line treatment,” rather than as a second-line therapy as in the current trial.
The researchers note that adverse events (AEs) “were generally mild (grade 1 or 2).”
The most common grade 3 adverse events in the combination arm were proteinuria (23%) and hypertension (20%), neither of which occurred at grade 3 or higher with osimertinib monotherapy.
Ten patients receiving osimertinib plus bevacizumab and five receiving osimertinib alone discontinued treatment due to AEs.
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