The role of osimertinib combinations as second-line treatment for advanced non-small cell lung cancer (NSCLC) is still unclear, according to researchers.
Osimertinib is a standard first-line treatment option for patients with advanced NSCLC and EGFR mutations, but progression on this treatment is inevitable, said Ross Soo, MD, of the National University Cancer Institute in Singapore.
He noted that preclinical data have implicated the angiogenic pathway in resistance to EGFR tyrosine kinase inhibitors (TKIs). Therefore, studies in the second-line setting are evaluating whether the efficacy of single-agent osimertinib can be improved with the addition of a VEGF inhibitor or other agents.1
In the phase 2 BOOSTER trial (ClinicalTrials.gov Identifier: NCT03133546), researchers compared bevacizumab plus osimertinib with osimertinib alone in patients who had NSCLC with sensitizing EGFR mutations (exon 19 del or L858R) and T790M mutations at progression on a prior EGFR TKI.
Dr Soo presented the trial’s results at a recent European Society for Medical Oncology (ESMO) Virtual Plenary.1
The results showed that adding bevacizumab to second-line osimertinib did not improve outcomes. However, exploratory analyses revealed a significant treatment interaction with a history of smoking.
The trial included 155 patients from 22 centers in 6 countries. The patients were randomly assigned to receive bevacizumab plus osimertinib (n=78) or osimertinib monotherapy (n=77). The median follow-up was 32.6 months in the combination arm and 34.5 months in the monotherapy arm.
The primary endpoint was progression-free survival (PFS), and there was no significant difference in PFS between the treatment arms. The median PFS was 15.4 months in the combination arm and 12.3 months in the monotherapy arm (hazard ratio [HR], 0.96; P =.84).
In the subgroup analysis, the effect of combination treatment was statistically significant among the current/former smokers compared with the never-smokers (PFS HRs, 0.57 and 1.29, respectively; P =.024).
With respect to overall survival (OS), there was no significant difference between the combination and monotherapy arms. The median OS was 24.0 months and 24.3 months, respectively (HR, 1.03; P =.91).
Likewise, there was no significant difference in OS between the current/former smoker and never-smoker subgroups (HRs, 0.64 and 1.40, respectively; P =.068).
The rate of grade 3 to 5 treatment-related adverse events (TRAEs) was higher in the combination arm than in the monotherapy arm — 47.4% and 18.2%, respectively. TRAEs that led to treatment discontinuation were also higher in the combination arm than in the monotherapy arm — 25.0% and 3.9%, respectively.
“Based on these findings, osimertinib remains the standard of care in patients with acquired EGFR TKI resistance harboring EGFR T790M mutations,” Dr Soo said.