Annals of Oncology: Academician Binghe Xu and Professor Tao Sun Report the OPTIMAL Study—Oral Paclitaxel Demonstrates Non-Inferiority to Intravenous Therapy in HER2-Negative Advanced Breast Cancer

On March 14, 2026, the international oncology journal Annals of Oncology (2025 IF: 65.4), the official journal of the European Society for Medical Oncology (ESMO), published the results of the international multicenter phase III OPTIMAL trial (NCT03315364). The study was led by Academician Binghe Xu (first author) from the National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences, and Professor S-B. Kim (corresponding author), with key contributions from Professor Tao Sun (Liaoning Cancer Hospital) and Professor H. Jeong (Asan Medical Center, University of Ulsan College of Medicine), among other international collaborators. For the first time, the study demonstrated that oral paclitaxel (DHP107) is non-inferior to weekly intravenous paclitaxel in first-line treatment of HER2-negative recurrent or metastatic breast cancer, with lower neurotoxicity and greater convenience—offering patients a safer and more accessible therapeutic option.

Paclitaxel in first-line therapy: intravenous vs oral—what are the differences?

Paclitaxel remains a cornerstone in breast cancer treatment, widely used across both early and advanced disease, and is included in the WHO Model List of Essential Medicines. Weekly intravenous paclitaxel has become a standard first-line option for HER2-negative advanced breast cancer due to its superior efficacy compared with every-three-week regimens.

However, intravenous administration presents several limitations. Oral bioavailability of conventional paclitaxel is extremely low (approximately 6.5%), necessitating intravenous infusion. Patients must visit hospitals regularly, with each infusion requiring several hours and premedication to prevent hypersensitivity reactions associated with the solvent Cremophor EL. Notably, Cremophor EL is also linked to paclitaxel-induced neurotoxicity, and some patients experience persistent peripheral neuropathy even after treatment discontinuation.

To overcome these challenges, the development of oral formulations has become a key focus. DHP107 (Liporaxel®) is a novel lipid-based oral paclitaxel formulation that enables effective absorption without the need for P-glycoprotein inhibitors. Previously, DHP107 demonstrated non-inferiority to intravenous paclitaxel in advanced gastric cancer and has been approved in both South Korea and China. Phase II studies in breast cancer also showed promising efficacy and manageable safety.

Against this backdrop, the OPTIMAL trial was designed to confirm the efficacy and safety of DHP107 compared with intravenous paclitaxel in HER2-negative advanced breast cancer.

The OPTIMAL trial: first phase III evidence supporting oral paclitaxel

The OPTIMAL study is an international, multicenter, randomized, open-label phase III non-inferiority trial. A total of 549 patients with HER2-negative recurrent or metastatic breast cancer from 51 centers across China, South Korea, and Europe were randomized 1:1 to receive either: • DHP107 (200 mg/m² orally, twice daily on days 1, 8, and 15), or • Intravenous paclitaxel (80 mg/m² on days 1, 8, and 15), in 28-day cycles.

The primary endpoint was investigator-assessed progression-free survival (PFS), with a predefined non-inferiority margin of HR ≤ 1.33.

In the per-protocol population, median PFS was 10.0 months in the DHP107 group versus 8.5 months in the intravenous group (HR=0.869; 95% CI 0.707–1.068), meeting the non-inferiority criterion.

Overall survival (OS) was 32.6 months vs 31.8 months (HR=0.967; 95% CI 0.762–1.227), while objective response rate (ORR) and disease control rate (DCR) were comparable between groups (43.3% vs 38.8% and 89.2% vs 84.4%, respectively).

Safety profile: distinct but manageable differences The safety profiles differed between the two formulations.

The oral DHP107 group showed higher rates of neutropenia (81.6% vs 59.3%), febrile neutropenia (6.1% vs 0.8%), and gastrointestinal events (nausea, diarrhea, vomiting), though most were grade 1–2 and clinically manageable.

In contrast, the intravenous paclitaxel group had higher incidences of peripheral neuropathy (48.3% vs 37.9%) and hypersensitivity reactions (2.7% vs 0.7%).

Importantly, quality-of-life assessments (EQ-5D-3L) were comparable between the two groups across all time points.

Academician Binghe Xu: toward a shift from hospital-based to home-based chemotherapy

The OPTIMAL study carries multiple important clinical implications. It represents the first phase III trial in breast cancer to demonstrate non-inferiority of oral paclitaxel compared with intravenous administration, filling a critical evidence gap.

The oral formulation also offers significant convenience—eliminating the need for hospitalization, intravenous access, and premedication—making it particularly beneficial for patients in remote areas or with limited mobility.

In an interview with Oncology Frontier, Academician Binghe Xu stated: “The results of the OPTIMAL study are highly encouraging. Oral paclitaxel demonstrates comparable efficacy to intravenous therapy, while offering clear advantages in reducing neurotoxicity and hypersensitivity reactions. For patients requiring long-term treatment, this translates into a lower treatment burden and improved quality of life. We believe DHP107 has the potential to become a new first-line option for HER2-negative advanced breast cancer and may help shift chemotherapy from a hospital-centered model toward a more home-based approach.”

He also noted that although neutropenia was more frequent in the oral group, it was manageable with dose adjustments and G-CSF support. Future studies are needed to validate long-term safety in real-world populations and explore combination strategies.

Additionally, the convenience of oral therapy may reduce healthcare system burden, including hospital visits and nursing costs, suggesting potential pharmacoeconomic advantages. With DHP107 already approved in China and South Korea, broader global adoption may follow.

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