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
M Shi, A Gu, H Tu, C Huang, H Wang, Z Yu, X Wang, L Cao, Y Shu, H Wang, R Yang, X Li, J Chang, Y Hu, P Shen, Y Hu, Z Guo, M Tao, Y Zhang, X Liu, Q Sun, X Zhang, Z Jiang, J Zhao, F Chen, H Yu, W Zhang, J Sun, D Li, J Zhou, B Han, Y L Wu, M Shi, A Gu, H Tu, C Huang, H Wang, Z Yu, X Wang, L Cao, Y Shu, H Wang, R Yang, X Li, J Chang, Y Hu, P Shen, Y Hu, Z Guo, M Tao, Y Zhang, X Liu, Q Sun, X Zhang, Z Jiang, J Zhao, F Chen, H Yu, W Zhang, J Sun, D Li, J Zhou, B Han, Y L Wu
Abstract
Background: Polymeric micellar paclitaxel (pm-Pac) is a novel Cremophor EL-free, nanoparticle micellar formulation of paclitaxel. We aimed to compare the efficacy and safety between pm-Pac plus cisplatin and solvent-based paclitaxel (sb-Pac) plus cisplatin in advanced non-small-cell lung cancer (NSCLC).
Patients and methods: A total of 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 end point was objective response rate (ORR) assessed by independent review committees (IRCs). The secondary end points 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 with those in the sb-Pac-plus-cisplatin group (50% versus 26%; rate ratio 1.91; P < 0.0001). Additionally, subgroup analysis showed that a higher ORR was consistently observed in both squamous and nonsquamous 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-month versus 5.3-month; hazard ratio 0.63; P = 0.0001). Median OS was not significantly different between the two groups. The incidence of treatment-related serious adverse events (9% versus 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.
Clinical trial identifier: ClinicalTrials.gov NCT02667743; https://ichgcp.net/clinical-trials-registry/NCT02667743.
Keywords: chemotherapy; non-small-cell lung cancer; pm-paclitaxel.
Conflict of interest statement
Disclosure YW has provided advisory or consultancy service and received personal fees from AstraZeneca, Boehringer Ingelheim, Merck, and Roche; has received institutional research funding from Boehringer Ingelheim and Roche; and has received honoraria from Eli Lilly, Pfizer, Pierre Fabre, Roche, and Sanofi. All other authors have declared no conflicts of interest.
Copyright © 2020 The Author(s). Published by Elsevier Ltd.. All rights reserved.
Source: PubMed