Cremophor-free paclitaxel noninferior to standard paclitaxel in ovarian cancer
A cremophor-free, polymeric micelle formulation of paclitaxel demonstrated noninferior efficacy and manageable toxicity compared with the standard paclitaxel regimen when added to carboplatin for first-line treatment of epithelial ovarian cancer, according to the KGOG-3021* study.
A total of 102 participants were randomized 1:1 to receive 5AUC** carboplatin combined with either cremophor-free, polymeric micelle-formulated paclitaxel 260 mg/m2 (study group) or standard paclitaxel 175 mg/m2 (control group) every 3 weeks. Of these, 98 were included in the intention-to-treat analysis. Drug administration commenced on day 1 of each 3-week cycle for a maximum of six cycles or until disease progression or the occurrence of dose-limiting toxicity. Median follow-up was 18.0 months. [Cancer Res Treat 2018;50:195-203]
Despite a higher overall response rate in the study vs the control group, the difference was nonsignificant (88.0 percent vs 77.1 percent; p=0.70), though lower than the noninferiority threshold (16.3 percent), indicating noninferiority of the study drug to the control drug.
Median time to progression was similar between the study and the control group (14.8 vs 15.4 months; p=0.55).
Toxicity events were numerically, but not significantly, higher in the study vs the control group (86.0 percent vs 77.1 percent; p=0.12 for neutropenia and 84.0 percent vs 64.6 percent; p=0.15 for peripheral neuropathy), and were successfully managed with conservative care.
These results mirror previous evidence showing less severe peripheral neuropathy and more rapid recovery with the solvent-free vs the conventional paclitaxel formulation. [J Clin Oncol 2005;23:7794-7803; Curr Neuropharmacol 2006;4:165-172]
Despite recent discoveries of targeted therapy and immunotherapy, paclitaxel remains the most important drug in ovarian cancer treatment, said the researchers. However, the commonly used solubilizer cremophor contributes to severe toxicities, including hypersensitivity reactions and potentially life-threatening events such as peripheral neuropathies, [Ann Pharmacother 2001;35:1114-1117; Br J Cancer 2004;90:304-305] hence the emergence of solvent-free formulations. [Eur J Cancer 2001;37:1590-1598; Cancer Chemother Pharmacol 2001;47:309-318]
“[Cremophor-free paclitaxel] allows administration of a greater paclitaxel dose without compromising patient safety [and] … seems to be efficacious [when added to carboplatin],” they said. “[These findings] may be a great help in selecting chemotherapeutic agents as first-line treatment for patients with ovarian cancer.”
These findings are also consistent with previous trials reflecting the tolerability and sufficient antitumour activity of the cremophor-free paclitaxel formulation in patients with metastatic breast cancer, non-small cell lung carcinoma, and urothelial carcinoma. [Breast Cancer Res Treat 2008;108:241-250; Invest New Drugs 2012;30:1984-1990]
Further studies using a larger sample are warranted to elucidate the superiority of cremophor-free over conventional paclitaxel, optimize the dose and schedule, and investigate long-term outcomes, including the reversibility of peripheral neuropathy, concluded the researchers.