Combination therapy with osimertinib and bevacizumab did not significantly improve progression-free survival (PFS) in treatment-naive patients with EGFR-mutated non–small cell lung cancer (NSCLC) when compared with osimertinib monotherapy, according to phase 2 study results presented at the 2021 European Society for Medical Oncology Congress.
The third-generation EGFR tyrosine kinase inhibitor osimertinib is a standard of care for treatment-naive patients with NSCLC and EGFR mutations. Because prior research suggested that erlotinib efficacy improved in this patient population when given in combination with an anti-VEGF inhibitor, researchers sought to determine whether the addition of bevacizumab would similarly boost the efficacy of osimertinib over monotherapy.
Hirotsugu Kenmotsu, MD, PhD, senior staff researcher at Shizuoka Cancer Center, Japan, and colleagues enrolled 122 patients with previously untreated nonsquamous NSCLC harboring Del19 or L858R EGFR mutations. Patients were assigned to daily osimertinib (80 mg) alone or in combination with bevacizumab (15 mg/kg every 3 weeks).
PFS served as the study’s primary endpoint. “Assuming that the median PFS in the [osimertinib and bevacizumab] arm and the [osimertinib] arm were 27 and 18 months, planned sample size was 120 in total to give a power of 80% with a one-sided alpha of 20%, with an accrual period of 1.5 years and a follow-up period of 2 years,” Kenmotsu and colleagues wrote.
In total, 61 patients were randomly assigned to each study arm between January and September 2018. The median follow-up was 19.8 months.
PFS by blinded independent central review was 22.1 months for patients assigned osimertinib and bevacizumab and 20.2 months for patients assigned osimertinib monotherapy (HR = 0.86; 60% CI, 0.7-1.06; 95% CI, 0.53-1.4).
According to the researchers, more favorable PFS responses to combination therapy were observed in patients who were former smokers (HR, 0.48) and patients with Del19 mutations (HR, 0.62).
Patients assigned to osimertinib and bevacizumab achieved an objective response rate of 82%, compared with 86% for patients assigned osimertinib monotherapy. Patients in the combination arm also had a higher proportion of grade 3 or grade 4 adverse events (56% vs. 48%).
The most common adverse events associated with combination therapy were any grade paronychia, rash acneiform, hypertension, epistaxis and proteinuria. Any grade pneumonitis occurred in 3% of the combination arm and 18% of the monotherapy arm. One patient in each arm developed grade 3 pneumonitis.
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