medwireNews: Combining erlotinib with bevacizumab is associated with a significant prolongation of progression-free survival (PFS) in chemotherapy-naïve patients with advanced nonsquamous non-small-cell lung cancer (NSCLC) harboring an activating EGFR mutation, indicates a phase III trial.
“These results suggest that combination therapy with bevacizumab and erlotinib has the potential to become a standard treatment for patients with EGFR-positive NSCLC if the overall survival data and quality of life analyses are favourable,” say the study authors in The Lancet Oncology.
Makoto Maemondo (Iwate Medical University School of Medicine, Morioka, Japan) and colleagues report the findings from an interim analysis of the NEJ026 trial that randomly assigned 224 patients with stage IIIB–IV or recurrent disease to receive the EGFR–tyrosine kinase inhibitor (TKI) erlotinib 150 mg/day, with or without the anti-VEGF antibody bevacizumab given at a dose of 15 mg/kg every 3 weeks. Participants had not received prior chemotherapy for advanced disease and were followed up for a median of 12.4 months.
Over this period, median PFS was 16.9 months for patients who received erlotinib plus bevacizumab and was 13.3 months for those who received erlotinib alone, a significant difference equating to a hazard ratio for progression or death of 0.605 in favor of the combination.
A post-hoc analysis by the type of EGFR mutation showed that the between-group difference in PFS remained significant for participants harboring Leu858Arg mutations, at a median of 17.4 and 13.7 months for the combination and erlotinib monotherapy arms, respectively. However, there was no significant difference between treatments among patients with exon 19 deletions.
Maemondo et al note that tumors driven by the Leu858Arg mutation “usually have an inferior response to EGFR TKIs” compared with those that have the exon 19 deletion as the oncogenic driver. But they also point out that the trial “was not powered for subgroup analysis” and these results should therefore “be interpreted with caution.”
In terms of the adverse event (AE) profile, events of grade 3 or worse occurred in 88% of participants in the bevacizumab–erlotinib group and 46% of those in the erlotinib alone group, with rash the most common grade 3–4 AE in both arms, at 21%.
Serious AEs were reported by 8% and 4% of patients given the combination and single-agent erlotinib, respectively, and there were no treatment-related deaths in either study group.
Twenty-nine percent of combination-treated participants discontinued bevacizumab due to AEs, while erlotinib was stopped by an identical 7% in the combination and monotherapy arms.
The NEJ026 trial was instigated to validate the positive findings from the phase II JO25567 study, say Maemondo and colleagues, and now they await the results of the phase III BEVERLY and Artemis trials, which are also evaluating the bevacizumab–erlotinib combination, to confirm their preliminary data.
medwireNews is an independent medical news service provided by Springer Healthcare. © 2019 Springer Healthcare part of the Springer Nature group
Lancet Oncol 2019; doi:10.1016/S1470-2045(19)30035-X
See also:
- Osimertinib best in first-line advanced NSCLC setting
- ARCHER 1050: Dacomitinib hits the OS target in advanced EGFR-mutated NSCLC
- Nivolumab plus ipilimumab benefits shown in highly mutated advanced NSCLC
- KEYNOTE-042: Pembrolizumab monotherapy supported for PD-L1-positive advanced NSCLC
- Atezolizumab boosts survival in metastatic nonsquamous NSCLC
- Icotinib advised for Chinese patients with metastatic NSCLC