Oral Paclitaxel Non-Inferior to IV Paclitaxel in HER2-Negative mBC

Oral paclitaxel (DHP107) shows comparable efficacy to intravenous (IV) paclitaxel and a tolerable and manageable safety profile in patients with HER2-negative metastatic breast cancer (mBC), according to results of the phase III OPTIMAL trial presented as an abstract at the 2025 American Society for Clinical Oncology Annual Meeting.

“DHP107 is a novel oral formulation of paclitaxel that is approved in South Korea and China for the treatment of gastric cancer,” explained the investigators. “DHP107 had encouraging monotherapy anti-tumor activity with objective response rate (ORR) of 55% and median progression free survival (PFS) of 8.9 months as first-line therapy in 31 patients with HER2-negative [mBC] in the OPTIMAL phase II study.”

The investigators reported the first primary analysis of the phase III portion of the open-label, randomized, controlled OPTIMAL trial (ClinicalTrials.gov ID: NCT03315364) evaluating non-inferiority of oral paclitaxel, DHP107, to IV paclitaxel in mBC, with a non-inferiority margin of 1.33.

The multi-national study enrolled patients from Korea, China, and Europe who had received at least one line of endocrine-based therapy and no chemotherapy for mBC. Patients were randomized (1:1) to receive either DHP107 (200 mg/m² oral, 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.

A total of 549 patients (median age, 56 years) were randomized. Most (88%) had hormone receptor-positive (HR-positive) disease, and 12% had triple-negative disease. The median follow-up duration was 38.8 months.

The investigators found that DHP107 was non-inferior to IV paclitaxel for the primary endpoint of investigator-assessed PFS (median PFS, 10.02 vs 8.54 months; hazard ratio [HR] 0.869, 95% confidence interval [CI], 0.707-1.068). They also observed comparable OS between the oral and IV paclitaxel arms (median OS, 32.95 vs 32.46 months; HR, 0.979; 95% CI, 0.769-1.246).

Patients in the DHP107 arm had higher ORR (45.8% vs 39.7%) and DCR (93.5% vs 86.4%) than those in the IV paclitaxel arm. The authors noted no significant differences in QOL outcomes. Median PFS findings for patients with HR-positive disease were similar to those of the overall population (10.74 vs 9.07 months; HR, 0.869; 95% CI, 0.700-1.080).

In the safety analysis, patients in the DHP107 arm had lower incidences of peripheral neuropathy (37.91% vs 48.29%), hypersensitivity reactions, musculoskeletal and connective tissue disorders, and injection/infusion-related reactions than those in the IV paclitaxel arm. Neutropenia was the most common adverse event in both groups and occurred more frequently in the DHP107 arm than the IV paclitaxel arm (81.6% [grade ≥3/4, 67.15%] vs 59.3% [29.66%]). Febrile neutropenia was also more frequent in the DHP107 arm than the IV paclitaxel arm (6.14% vs 0.76%; no grade 5 events). Gastrointestinal toxicities, which were mostly grade 1, were more frequent in the DHP107 arm than in the IV paclitaxel arm. The rate of discontinuation due to AEs was comparable between the DHP107 and IV paclitaxel arms (12.27% vs 8.75%; P=0.208). AEs leading to death occurred in both the DHP107 and IV paclitaxel arms (1.08% vs 1.90%).

“DHP107 demonstrated comparable efficacy to IV paclitaxel with tolerable and manageable toxicity,” concluded the investigators. “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.”

Disclosure: This research was supported by Daewha Pharm. Co., Ltd. Please see the original reference for a full list of disclosures.