A new analysis from the COMPEL trial showed that patients with EGFR-mutated advanced non–small cell lung cancer (NSCLC) who experienced non–central nervous system (CNS) disease progression on first-line osimertinib benefit from continuing osimertinib treatment in combination with platinum-based chemotherapy.
The study was presented at the International Association for the Study of Lung Cancer 2025 World Conference on Lung Cancer (Abstract OA08.03).
The COMPEL study is a global, randomized, double-blind trial in which adult patients with non-CNS progression on first-line osimertinib were randomly assigned 1:1 to receive either osimertinib at 80 mg once daily or placebo once daily in combination with platinum/pemetrexed chemotherapy (cisplatin at 75 mg/m2 or carboplatin at area under the curve 5 plus pemetrexed at 500 mg/m2 every 3 weeks for four cycles), followed by osimertinib at 80 mg once daily or placebo once daily in combination with maintenance pemetrexed (500 mg/m2 every 3 weeks) until disease progression or another discontinuation criterion was met.
The study showed that continuing osimertinib with the addition of platinum/pemetrexed chemotherapy was associated with improved progression-free survival compared with placebo plus chemotherapy (hazard ratio [HR] = 0.43, 95% confidence interval [CI] = 0.27–0.70); median progression-free survival was 8.4 months with osimertinib plus chemotherapy vs 4.4 months with placebo plus chemotherapy. Median overall survival was also longer with osimertinib plus chemotherapy (15.9 months) vs placebo plus chemotherapy (9.8 months; HR = 0.71, 95% CI = 0.42–1.23).
“These results indicate that resistance to first-line osimertinib may be heterogeneous, and some tumor cells remain sensitive to continued therapy,” said lead investigator Giulia Pasello, MD, PhD, of the Veneto Institute of Oncology IOV-IRCCS in Italy. “This trial supports osimertinib as a backbone treatment strategy in this setting.”
Dr. Pasello reported that the safety and tolerability profile of the combination therapy was manageable and consistent with the known safety profiles of osimertinib and chemotherapy agents. The findings also align with results from the FLAURA2 study, which showed a benefit for first-line osimertinib combined with chemotherapy.
These results may help inform treatment decisions and emphasize the importance of personalized strategies for patients with EGFR-mutated advanced NSCLC following progression on targeted therapy, concluded Dr. Pasello.
Disclosure: For full disclosures of the study authors, visit cattendee.abstractsonline.com.
