Phase III of oral paclitaxel (DHP107) vs intravenous paclitaxel in HER2-negative recurrent or metastatic breast cancer (mBC): Primary analysis of a multinational optimal trial (NCT03315364).

Background: DHP107 is a novel oral formulation of paclitaxel that is approved in South Korea and China for the treatment of gastric cancer. DHP107 had encouraging monotherapy anti-tumor activity with objective response rate (ORR) of 55% and median progression free survival (PFS) of 8.9 months (Mo) as first-line therapy in 31 patients with HER2 negative metastatic breast cancer (mBC) in the OPTIMAL phase II study (Kim Ther Adv Med Oncol 2021). The first primary analysis is reported herein. Methods: This phase III, open-label, randomized, controlled trial evaluated the non-inferiority of DHP107 to intravenous (IV) paclitaxel in mBC, with non-inferiority margin of 1.33. Patients (Pts) had received one or more lines of endocrine-based therapy and no chemotherapy for mBC. Pts from Korea, China, and Europe were randomized 1:1 to receive either DHP107 (200 mg/m² orally, twice daily) or IV paclitaxel (80 mg/m² weekly). The primary endpoint was investigator-assessed PFS. Secondary endpoints included overall survival (OS), ORR, disease control rate (DCR), quality of life (QoL), and safety. Results: With the median follow-up of 38.8 Mo, the median age of the pts was 56 years. Of the 549 pts who underwent randomization, 481 pts had hormone receptor positive (HR+) disease and 68 pts had triple negative disease. Among all pts, DHP107 demonstrated non-inferiority to IV paclitaxel in PFS (mPFS: 10.02 vs. 8.54 Mo; HR 0.869, 95% CI 0.707–1.068). OS was comparable between groups (mOS: 32.95 vs. 32.46 Mo; HR 0.979, 95% CI 0.769–1.246). Among HR+HER2-pts, the mPFS was 10.74 Mo in the DHP107 arm, and 9.07 Mo in IV paclitaxel arm (HR 0.869, 95% CI 0.700-1.080). QoL outcomes showed no significant differences. ORR (45.8% vs. 39.7%) ad DCR (93.5% vs. 86.4%) were higher in the DHP107 group. DHP107 was associated with lower incidences of peripheral neuropathy (37.91% vs. 48.29%), hypersensitivity reactions, musculoskeletal and connective tissue disorders, and injection/infusion related reactions compared to IV paclitaxel. Neutropenia was the most common toxicity in both groups, occurring more frequently in the DHP107 group (81.6% vs. 59.3%) with higher rates of Gr≥3,4 neutropenia (67.15% vs. 29.66%), and febrile neutropenia (6.14% vs. 0.76%), but no grade 5 events were reported. Gastrointestinal toxicities were more frequent in the DHP107 group but were predominately Gr1. In this study, discontinuation rate due to AEs were comparable (12.27% vs. 8.75%, p=0.2081) and AEs leading to death occurred rarely in both groups (1.08% vs. 1.90%). Conclusions: DHP107 demonstrated comparable efficacy to IV paclitaxel with tolerable and manageable toxicity. These results establish DHP107 as an effective, convenient alternative to IV paclitaxel for patients with HER2-negative mBC, supporting its potential role in routine clinical practice. Clinical trial information: NCT03315364.ResearchSponsor:DAEWHAPHARM. CO., LTD.