OPTIMAL: A Multinational Phase III Study of Oral Paclitaxel (DHP107) versus Intravenous Weekly Paclitaxel in HER2-Negative Recurrent or Metastatic Breast Cancer
Mené sur 549 patientes atteintes d'un cancer du sein HER2- récidivant ou métastatique, cet essai international de phase III compare l'efficacité, du point de vue de la survie sans progression, et la toxicité de deux modes d'administration du paclitaxel (voie orale ou intraveineuse)
Background: Intravenous (IV) paclitaxel 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 to IV 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 non-inferiority of DHP107 compared to IV paclitaxel, with a predefined non-inferiority margin of 1.33. Eligible patients had recurrent or metastatic breast cancer and had received no prior chemotherapy in the metastatic setting. Patients were randomized to receive either 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. 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 (QoL), and safety.
Results: Between January 2018 and December 2023, 549 patients were randomized to receive either DHP107 (n=277) or paclitaxel (n=272); 519 patients were included in the PPS. DHP107 demonstrated non-inferiority in PFS with a median PFS of 10.0 months compared to 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 in one patient (0.4%) in the paclitaxel group. Quality of life was comparable between the two groups.
Conclusions: DHP107 demonstrated non-inferior efficacy compared to IV paclitaxel, with a manageable safety profile, supporting its use as an effective and convenient alternative in HER2-negative breast cancer.
Annals of Oncology , résumé, 2026