OPTIMAL: a multinational phase III study of oral paclitaxel (DHP107) versus intravenous weekly paclitaxel in HER2-negative recurrent or metastatic breast cancer

Ann Oncol. 2026 Jul;37(7):936-945. doi: 10.1016/j.annonc.2026.03.002. Epub 2026 Mar 14.

Abstract

Background: Intravenous (i.v.) paclitaxel (Taxol) requires prolonged infusion and is associated with hypersensitivity reactions and peripheral neuropathy. This study evaluated the efficacy and safety of DHP107, a novel oral formulation of paclitaxel, compared with i.v. paclitaxel in patients with HER2-negative, recurrent, or metastatic breast cancer.

Patients and methods: This multinational, multicenter, open-label, randomized phase III trial evaluated the noninferiority of DHP107 compared with i.v. paclitaxel, with a predefined noninferiority margin of 1.33. Eligible patients had recurrent or metastatic breast cancer and had received no prior chemotherapy in the metastatic setting. Patients were randomly assigned to receive either DHP107 (200 mg/m2 orally twice daily on days 1, 8, and 15) or paclitaxel (80 mg/m2 i.v. on days 1, 8, and 15) in a 28-day cycle. The primary endpoint was investigator-assessed progression-free survival (PFS) in the per-protocol set (PPS). Secondary endpoints included independent central review-assessed PFS, overall survival (OS), tumor response, quality of life, and safety.

Results: Between January 2018 and December 2023, 549 patients were randomly assigned to receive either DHP107 (n = 277) or paclitaxel (n = 272); 519 patients were included in the PPS. DHP107 demonstrated noninferiority in PFS with a median PFS of 10.0 months compared with 8.5 months for paclitaxel (hazard ratio [HR] 0.869; 95% confidence interval [CI] 0.707-1.068). The median OS was 32.6 months for DHP107 and 31.8 months for paclitaxel (HR 0.967, 95% CI 0.762-1.227). DHP107 was associated with higher rates of neutropenia, febrile neutropenia, nausea, diarrhea, and vomiting, whereas peripheral neuropathy and hypersensitivity reactions were more common with paclitaxel. No treatment-related death occurred in the DHP107 group, and one (0.4%) in the paclitaxel group. Quality of life was comparable between the two groups.

Conclusions: DHP107 demonstrated noninferior efficacy compared with i.v. paclitaxel, with a manageable safety profile, supporting its use as an effective and convenient alternative in HER2-negative breast cancer.

Keywords: DHP107; metastatic breast cancer; non-inferiority; oral paclitaxel; phase III.

Publication types

  • Multicenter Study
  • Clinical Trial, Phase III
  • Randomized Controlled Trial
  • Equivalence Trial
  • Comparative Study

MeSH terms

  • Administration, Oral
  • Adult
  • Aged
  • Antineoplastic Agents, Phytogenic* / administration & dosage
  • Antineoplastic Agents, Phytogenic* / adverse effects
  • Breast Neoplasms* / drug therapy
  • Breast Neoplasms* / mortality
  • Breast Neoplasms* / pathology
  • Drug Administration Schedule
  • Erb-b2 Receptor Tyrosine Kinases / metabolism
  • Female
  • Humans
  • Middle Aged
  • Neoplasm Metastasis
  • Neoplasm Recurrence, Local* / drug therapy
  • Neoplasm Recurrence, Local* / pathology
  • Paclitaxel* / administration & dosage
  • Paclitaxel* / adverse effects
  • Progression-Free Survival
  • Quality of Life

Substances

  • Paclitaxel
  • Erb-b2 Receptor Tyrosine Kinases
  • ERBB2 protein, human
  • Antineoplastic Agents, Phytogenic