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

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/m 2 ) plus cisplatin (70 mg/m 2 ; n ¼ 300), followed by dose escalation of pm-Pac to 300 mg/m 2 from the second 3-week cycle if prespecified toxic effects were not observed after the first cycle, or sb-Pac (175 mg/m 2 ) plus cisplatin (70 mg/m 2 ; n ¼ 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-pluscisplatin group (6.4-month versus 5.3-month; hazard ratio 0.63; P ¼ 0.0001). Median OS was not significantly

Efficacy and Safety of Nanoadministration in the Treatment of Non-Small-Cell Lung Cancer Is Good to Some Extent: A Systematic Review and Meta-Analysis

“…The results of M. Shi et al (2020) [ 23 ] showed that compared with Sb-P/C, Pm-P/C significantly improved ORR and PFS in patients with advanced NSCLC, but there was no significant difference in OS. Subgroup analysis showed that Sb-P/C has PFS and OS advantages over Pm-P/C in patients with PS (performance status) 0.…”

“…In our analysis, the results of M. Shi et al (2020) showed significant differences in ORR and PFS, which were different from the results of the other five RCT analyses, which may be related to the fact that the research object was Chinese and the experimental group intervention was Pm-P/C. As a nanodrug, polymeric micellar paclitaxel (pm-Pac) could passively target tumors by enhancing permeability and retention effects, significantly reducing the retention of paclitaxel in the blood, thereby enhancing drug uptake and accumulation in tumor tissues [ 23 , 34 , 35 ]. Vera Hirsh et al (2016) [ 24 ] concluded that nab-paclitaxel plus carboplatin (nab-P/C) demonstrated improved efficacy and manageable tolerability in patients with advanced NSCLC and diabetes.…”

Microtubule-Interfering Drugs: Current and Future Roles in Epithelial Ovarian Cancer Treatment

“…EndoTAG-1 ® (MediGene, Melbourne, VIC, Australia) contains cationic liposomes and paclitaxel, with specific anti-angiogenic activity; it remains under investigation in the phase III setting for pancreatic cancer [ 123 ]. Polymeric micellar paclitaxel (Genexol-PM ® , Samyang Genex Co., Gyeonggi-do, Korea; Shanghai Yizhong Biotechnical Co., Ltd. Shanghai, China) has recently demonstrated improved response rates and survival compared to paclitaxel in non-small cell lung cancers [ 124 ].…”

Remodeling tumor microenvironment with nanomedicines

“…For example, the paclitaxel‐loaded polymeric micelles NK105 with 85 nm and the docetaxel‐loaded nanoparticles BIND‐014 with approximately 100 nm in diameter failed to meet their clinical endpoints in phase III clinical trials against breast cancer and in phase II clinical trials against nonsmall cell lung cancer (NSCLC), respectively (Mi et al, 2021). On the other hand, paclitaxel‐loaded polymeric micelles with a relatively smaller diameter of 20 nm have recently shown superior objective response rate (ORR) and progression‐free survival (PFS) in combination with cisplatin compared to solvent‐based paclitaxel plus cisplatin in a Phase III clinical study in patients with advanced NSCLC (NCT02667743) (Shi et al, 2021). As more NMs make progress into the clinic, the precise size range of NM for targeting clinical tumors will be clarified.…”