(Barcelona, Spain September 6, 2025, 5:45 p.m. CEST / UTC +2 ) — A new analysis from the COMPEL trial shows that patients with EGFR-mutated (EGFRm) advanced non-small cell lung cancer (NSCLC) who experienced non-central nervous system (CNS) progression on first-line osimertinib benefit from continuing osimertinib treatment in combination with platinum-based chemotherapy.
The study was presented today at the International Association for the Study of Lung Cancer 2025 World Conference on Lung Cancer (WCLC).
The COMPEL study is a global, randomized, double-blind trial, in which adult patients with non-CNS progression on first-line osimertinib were randomized 1:1 to receive either osimertinib 80 mg once daily or placebo once daily in combination with platinum-pemetrexed chemotherapy (cisplatin 75 mg/m2 or carboplatin AUC5 + pemetrexed 500 mg/m2 every 3 weeks for 4 cycles), followed by osimertinib 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 (PFS) compared with placebo plus chemotherapy (HR: 0.43; 95% CI: 0.27–0.70); median PFS was 8.4 months with osimertinib plus chemotherapy vs. 4.4 months with placebo plus chemotherapy. Median overall survival (OS) 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 Dr. Giulia Pasello 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 EGFRm advanced NSCLC following progression on targeted therapy, said Dr. Pasello.
About the IASLC:
The International Association for the Study of Lung Cancer (IASLC) is the only global organization dedicated solely to the study of lung cancer and other thoracic malignancies. Founded in 1974, the association's membership includes more than 10,000 lung cancer specialists across all disciplines in over 100 countries, forming a global network working together to conquer lung and thoracic cancers worldwide. The association also publishes the Journal of Thoracic Oncology, the primary educational and informational publication for topics relevant to the prevention, detection, diagnosis, and treatment of all thoracic malignancies. Visit www.iaslc.org for more information.
About the WCLC:
The WCLC is the world’s largest meeting dedicated to lung cancer and other thoracic malignancies, attracting nearly 7,000 researchers, physicians, and specialists from more than 100 countries. The goal is to increase awareness, collaboration and understanding of lung cancer, and to help participants implement the latest developments across the globe. The conference will cover a wide range of disciplines and unveil several research studies and clinical trial results. For more information, visit https://wclc.iaslc.org/.