Impact of Subsequent Immune Checkpoint Inhibitor Treatment on Overall Survival With Avelumab vs Docetaxel in Platinum-Treated Advanced NSCLC: Post Hoc Analyses From the Phase 3 JAVELIN Lung 200 Trial
Mené sur des patients atteints d'un cancer du poumon non à petites cellules de stade IIIB/IV, cet essai de phase III compare l'efficacité, du point de vue de la survie globale, de l'avélumab et du docétaxel, après l'échec d'une chimiothérapie à base de sels de platine (durée médiane de suivi : 10,5 mois)
Objectives : The JAVELIN Lung 200 phase 3 trial did not meet its primary endpoint of improving overall survival (OS) with avelumab vs docetaxel in patients with platinum-treated PD-L1+ NSCLC. We report post hoc analyses assessing the effects of subsequent immunecheckpoint inhibitor (ICI) treatment on OS. Material and methods : Patients with stage IIIB/IV NSCLC progressed following platinum-doublet therapy wererandomized to receive avelumab or docetaxel. OS was analyzed in the PD-L1+ population(≥1% of tumor cells) and full analysis set (PD-L1+ or PD-L1−). Effects of subsequent ICI (after permanent discontinuation of study treatment) on OS were analyzed usinga preplanned naive sensitivity analysis and post hoc inverse probability of censoring weighting (IPCW) analysis. Subgroups with or without subsequent ICI treatment wereanalyzed using descriptive statistics. Results : In the avelumab and docetaxel arms, a subsequent ICI was received by 16/396 (4.0%)and 104/396 (26.3%) after a median of 10.5 months (range, 3.9-20.4) and 5.7 months(range, 0.1-24.4), respectively. Some subgroups showed trends for higher subsequentICI treatment, including patients with non-squamous NSCLC (avelumab arm, 4.3% vs docetaxelarm, 32.1%) or with a baseline ECOG performance status score of 0 (6.3% vs 31.3%);those enrolled in the early recruitment wave (11.6% vs 54.3%), or enrolled in theUS/Western Europe (2.8% vs 45.5%) or Asia (11.0% vs 35.4%); and non-white patients(10.1% vs 35.0%). The hazard ratio for OS with avelumab vs docetaxel was lower inthe IPCW analysis than in the naive sensitivity analysis (PD-L1+ population: 0.80[95% CI, 0.62-1.04] vs 0.86 [95% CI, 0.68-1.09], respectively). Conclusion : In the JAVELIN Lung 200 trial, avelumab showed clinical activity as second-line treatment for patients with advanced NSCLC. Post hoc analyses suggest that the primary OS analysismay have been confounded by subsequent ICI use in the docetaxel arm. ClinicalTrials.govidentifier: NCT02395172.
Lung Cancer 2021