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.

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.