Comparing Nanoparticle Polymeric Micellar Paclitaxel and Solvent-based Paclitaxel as First-line Treatment of Advanced Non-Small Cell Lung Cancer: An Open-label, Randomized, Multicenter, Phase III Trial
Mené sur 448 patients atteints d'un cancer du poumon non à petites cellules de stade avancé, cet essai de phase III compare l'efficacité, du point de vue du taux de réponse objective, et la toxicité d'un traitement de première ligne utilisant une formulation micellaire de nanoparticules chargées en paclitaxel et d'un traitement utilisant du paclitaxel avec solvant, tous deux combinés au cisplatine
Background : Polymeric micellar paclitaxel (pm-Pac) is a novel Cremophor EL (CrEL)-free, nanoparticle micellar formulation of paclitaxel. We aimed to compare the efficacy and safety between pm Pac plus cisplatin and sb-Pac (solvent-based paclitaxel) plus cisplatin in advanced non–small cell lung cancer (NSCLC). Patients and Methods : 448 stage IIIB to IV NSCLC patients were randomly assigned (2:1) to receive six 3-week cycles of either pm-Pac (230 mg/m2) plus cisplatin (70 mg/m2) (n=300), followed by dose escalation of pm-Pac to 300 mg/m2 from the second 3-week cycle if prespecified toxic effects were not observed after the first cycle, or sb-Pac (175 mg/m2) plus cisplatin (70 mg/m2) (n=148). The primary endpoint was objective response rate (ORR) assessed by independent review committees (IRC). The secondary endpoints included IRC-assessed progression-free survival (PFS), overall survival (OS), and safety. Results : Patients in the pm-Pac-plus-cisplatin group showed significant improvements in IRC-assessed ORR compared to those in the sb-Pac-plus-cisplatin group (50% vs. 26%; RR 1.91; p<0.0001). Additionally, subgroup analysis showed that a higher ORR was consistently observed in both squamous and non-squamous histological types. IRC-assessed median PFS was significantly higher in the pm-Pac-plus-cisplatin group than in the sb-Pac-plus-cisplatin group (6.4-months vs. 5.3-months) (hazard ratio [HR] 0.63; p=0.0001). Median OS was not significantly different between the two groups. The incidence of treatment-related serious adverse events (9% vs. 18%; p=0.0090) was significantly lower in the pm-Pac-plus-cisplatin group than in the sb-Pac-plus-cisplatin group. Conclusion : Pm-Pac plus cisplatin yielded superior ORR and PFS along with a favorable safety profile and should become an option for patients with advanced NSCLC.
Annals of Oncology 2020