Final overall survival analysis of the APPLE study: atezolizumab and platinum-pemetrexed with or without bevacizumab for metastatic nonsquamous non-small cell lung cancer
Mené sur 412 patients atteints d'un cancer du poumon non à petites cellules non épidermoïde de stade avancé (durée de suivi : 3,5 ans), cet essai de phase III évalue l'efficacité, du point de vue de la survie sans progression et de la survie globale, et la toxicité de l'ajout de bévacizumab à un traitement combinant atézolizumab et sels de platine/pémétrexed, en fonction de l'expression tumorale de PD-L1 et du statut des oncogènes (positif/négatif)
Background: The phase III APPLE trial evaluated the efficacy of adding bevacizumab to atezolizumab with carboplatin plus pemetrexed (APP) for individuals with advanced nonsquamous non–small cell lung cancer (NSCLC). We here report the long-term outcomes of this trial with 3.5 years of follow-up.
Methods: Patients with advanced nonsquamous NSCLC were randomized 1:1 to receive APP or APP plus bevacizumab (APPB). Stratification factors were clinical stage, driver oncogenes, and PD-L1 expression. Endpoints included progression-free survival, overall survival (OS), and safety.
Results: A total of 412 patients were enrolled; 1 patient was excluded from the intention-to-treat population. Of the remaining patients, 287 patients were classified as driver oncogene–negative and 124 as driver oncogene–positive. The updated median OS was 28.0 months in the APPB arm and 25.7 months in the APP arm, with a hazard ratio (HR) of 0.88 (95% confidence interval [CI], 0.70–1.10). For the driver oncogene–negative population, the median OS was 27.6 months in the APPB arm and 27.8 months in the APP arm (HR of 0.96 [95% CI, 0.73–1.27]), with the corresponding values for the driver oncogene–positive population being 28.0 and 20.8 months (HR of 0.71 [95% CI, 0.47–1.08]). Safety profiles did not change from earlier analysis.
Conclusions: The addition of bevacizumab to APP did not improve OS in patients with advanced nonsquamous NSCLC. In the driver oncogene–positive subgroup, favorable OS trend was observed in the bevacizumab arm, highlighting its potential as a treatment option for individuals who have failed molecular-targeted therapy.
Lung Cancer , article en libre accès, 2026