As reported in the Journal of Clinical Oncology by Jordi Remon, MD, PhD, and colleagues, the final analysis of overall survival in the phase II EORTC APPLE trial showed no significant difference between the strategies of upfront osimertinib vs sequential gefitinib/osimertinib in previously untreated patients with advanced EGFR-mutant non–small cell lung cancer (NSCLC).
Jordi Remon, MD, PhD
Study Details
In the multicenter trial, 156 patients were allocated between November 2017 and February 2020 to one of two treatment strategies: upfront osimertinib (n = 53) or upfront gefitinib followed by osimertinib at either molecular progression (detection of plasma T790M resistance mutation) regardless of radiologic status or at time of radiologic progression (n = 103). Of these, 45 and 91 patients were evaluable for efficacy, respectively.
Key Findings
In the osimertinib group, 20 (44%) of 45 patients had disease progression and received subsequent platinum-based chemotherapy (n = 10), osimertinib beyond progression alone (n = 3) or in combination with radiotherapy (n = 3), or other treatments (n = 4). Among the remaining 25 patients, 16 were still receiving osimertinib at the time of analysis and 9 had stopped treatment.
In the sequential group, 66 (73%) of 91 patients switched to osimertinib per protocol, and an additional 6 (7%) received osimertinib outside the trial. Among the remaining 19 patients, 9 received other targeted agents, 6 patients were still receiving gefitinib, and 4 had stopped treatment.
Median overall survival was not reached in the osimertinib group vs 42.8 months (95% confidence interval [CI] = 28.6 months to not reached) in the sequential group (hazard ratio [HR] = 1.01, 90% CI = 0.61–1.68); rates at 18 months were 84% vs 82.3%. The osimertinib group had significantly better brain progression-free survival, with a hazard ratio for brain progression of 0.54 (90% CI = 0.34–0.86).
The investigators concluded, “The APPLE trial suggests that a sequential treatment approach is associated with more frequent progression in the brain but a similar survival in advanced EGFR-mutant NSCLC.”
Rafal Dziadziuszko, MD, PhD, of the Department of Oncology and Radiotherapy and Early Phase Clinical Trials Center, Medical University of Gdánsk, Poland, is the corresponding author for the Journal of Clinical Oncology article.
Disclosure: The study was supported by AstraZeneca. For full disclosures of the study authors, visit ascopubs.org.
