A novel oral formulation of paclitaxel, DHP107, is noninferior to weekly intravenous (IV) paclitaxel in the treatment of HER2-negative recurrent or metastatic breast cancer, as shown by the results of the phase III OPTIMAL study.
“With its noninferior efficacy, manageable safety profile, comparable quality-of-life outcomes, and the convenience of oral administration, DHP107 offers a convenient, noninferior alternative to IV paclitaxel for patients with HER2-negative metastatic breast cancer, supporting its use as a viable option in routine clinical practice,” the investigator said.
A total of 549 patients were randomized to receive either DHP107 (n=277) or paclitaxel (n=272) between January 2018 and December 2023. Of these, 519 were included in the per-protocol set (PPS). [Ann Oncol 2026;37:936-945]
Noninferiority was established for DHP107, with a median progression-free survival (PFS) of 10.0 months relative to 8.5 months for IV paclitaxel (hazard ratio [HR], 0.869, 95 percent confidence interval [CI], 0.707‒1.068). The median overall survival (OS) was also comparable between the two groups (32.6 months vs 31.8 months, respectively; HR, 0.967, 95 percent CI, 0.762‒1.227).
Likewise, the objective response rates did not significantly differ between DHP107 and IV paclitaxel (43.3 percent vs 38.8 percent).
DHP107 also had an acceptable safety profile. Its use was associated with increased rates of nausea, diarrhoea, vomiting, neutropenia, and febrile neutropenia. Moreover, the use of paclitaxel appeared to have caused some patients to develop peripheral neuropathy and hypersensitivity reactions.
None of the patients in the DHP107 group died due to the treatment, but one (0.4 percent) did in the paclitaxel group. Quality of life was similar between the two groups.
Advantages
“[T]he self-administered oral formulation of DHP107 does not require premedication, offering additional benefits such as fewer hypersensitivities and infusion reactions compared with IV paclitaxel, which necessitates premedication,” the investigators said.
The advantages of DHP107 seen in this study support the findings from the phase III DREAM trial in advanced gastric cancer and the phase II trial in metastatic breast cancer. [Ann Oncol 2018;29:1220-1226; Ann Oncol 2022;33:S658]
“Moreover, oral administration eliminates the need for weekly IV infusions, reducing clinical visits and improving patient convenience,” the investigators said.
“This may be particularly beneficial for patients with limited access to infusion facilities or those residing in remote areas, and it may also reduce overall administration costs without compromising efficacy or quality of life,” they added. [Am J Manag Care 2021;27:SP46-SP50]
DHP107
OPTIMAL is a multinational, multicentre, open-label, randomized phase III trial that assessed the noninferiority of DHP107 compared with IV paclitaxel. The predefined noninferiority margin was 1.33.
The study included patients with recurrent or metastatic breast cancer who had not received prior chemotherapy in the metastatic setting. Eligible participants were randomly allocated to receive DHP107 200 mg/m2 orally twice daily on days 1, 8, and 15 or paclitaxel 80 mg/m2 intravenously on days 1, 8, and 15 in a 28-day cycle.
An investigator-assessed PFS in the PPS served as the primary endpoint, while secondary endpoints included independent central review-assessed PFS, OS, tumour response, quality of life, and safety.
“DHP107 is a muco-adhesive, lipid-based oral paclitaxel formulation that enables systemic absorption without the need for Cremophor EL,” the investigators said. [Mol Cancer Ther 2007;6:3239-3247; Invest New Drugs 2013;31:616-622]
“[I]t does not require co-administration of P-glycoprotein inhibitors, which are multidrug transporters in the intestinal mucosa that limit the bioavailability of paclitaxel,” they added. [Proc Natl Acad Sci U S A 1997;94:2031-2035]