Median progression-free survival (PFS) was 20.2 months in 61 patients in the osimertinib monotherapy arm and 22.1 months in 61 patients in the combination treatment arm (hazard ratio, 0.862), Hirotsugu Kenmotsu, MD, PhD, reported at the 2021 Congress of the European Society for Medical Oncology Sept. 18 (abstract LBA44).
“The study did not meet the primary endpoint,” said Dr. Kenmotsu of Shizuoka Cancer Center, Nagaizumi, Japan. “One-year progression-free survival was 63.7% and 73.8%, respectively.
However, subgroup analyses showed a trend toward improved PFS with combination bevacizumab and osimertinib in ever-smokers (HR, 0.481) and patients with Del19 mutations (HR, 0.622), he said.
Bevacizumab was also associated with a significant reduction in the risk of pneumonitis, an interstitial lung disease (ILD): Pneumonitis occurred in 18.3% of patients in the combination therapy arm, compared with 3.3% in the osimertinib monotherapy arm.
Study participants were untreated patients with advanced nonsquamous NSCLC harboring an EGFR-sensitizing mutation – either Del19 or L858R – without symptomatic brain metastases. They were enrolled between January 2018 and September 2018 and randomized to receive 80 mg of osimertinib daily, either alone or with 15 mg/kg of bevacizumab every 3 weeks.
The objective response rate was 82% in the combination therapy arm and 86% in osimertinib monotherapy arm, Dr. Kenmotsu said, adding that overall survival data are not yet mature.
Grade 3-4 adverse events occurred in 34 patients (56%) in the combination therapy arm and in 29 patients (48%) in the osimertinib monotherapy arm, he noted.
Osimertinib, a third-generation EGFR tyrosine kinase inhibitor has been a standard first-line treatment for NSCLC harboring activating EGFR mutations, he explained, noting that prior studies have shown promise for improved PFS with the addition of antivascular endothelial growth factor inhibitors to first-generation EGFR TKIs in this population.
Although the current study failed to show efficacy of the combination therapy versus osimertinib monotherapy for improving PFS in nonsquamous NSCLC harboring EGFR mutation, ever-smokers and patients with exon 19 deletions might benefit from the combination therapy as first-line treatment, and the combination might also reduce the risk of osimertinib-related pneumonitis, Dr. Kenmotsu said.
The study is among those that address “really important questions in lung cancer today,” said invited discussant Natasha B. Leighl, MD, professor of medicine at the University of Toronto’s Princess Margaret Cancer Center.
“I certainly agree with the authors that this study is a negative trial and bevacizumab does not improve PFS over the standard of osimertinib alone,” she said, acknowledging that the study is the first randomized comparison of the two treatment approaches in the first-line setting. She also agreed with the authors that the subgroup findings are intriguing.
“But ... what is the biomarker?” she asked, referring to the “very interesting” finding of a possible bevacizumab benefit among ever-smokers. “I’m looking forward to more correlative studies to help define this further.”
The novel finding of a significantly reduced risk of pneumonitis with the addition of bevacizumab, on the other hand, is “extremely exciting,” she said, explaining that the combination therapy approach could “perhaps [be used] as a potential therapy for patients with TKI-induced ILD and no other options, or those at very high risk of ILD, for example, perhaps, post immunotherapy or in high-risk populations.”
This study was funded by AstraZeneca. Dr. Kenmotsu and Dr. Leigh each disclosed financial relationships with numerous pharmaceutical companies.
This article was updated Sept. 24, 2021.