Oral Paclitaxel DHP107 Non-inferior to IV for Metastatic Breast Cancer

Patients with HER2-negative metastatic breast cancer may soon have a more convenient treatment option, as the phase 3 OPTIMAL trial (NCT03315364) confirms that DHP107, a novel oral paclitaxel formulation, is non-inferior to traditional intravenous (IV) paclitaxel.

From January 2018 to December 2023, researchers at 51 sites across South Korea, China, and Europe evaluated 549 patients to determine if an oral regimen could match the efficacy of weekly IV infusions while reducing the clinical burden of prolonged administration and premedication. The results, published in Annals of Oncology, demonstrate that DHP107 successfully met its primary endpoint of progression-free survival (PFS), offering a viable alternative that eliminates the need for IV access and reduces the risk of peripheral neuropathy.

Main data that support the findings

The primary endpoint of investigator-assessed progression-free survival (PFS) met the predefined non-inferiority margin of 1.33. In the per-protocol set (PPS), the median PFS was 10.0 months (95% CI, 9.1–11.2) for the DHP107 group compared to 8.5 months (95% CI, 7.4–9.3) for those receiving IV paclitaxel (hazard ratio [HR], 0.869; 95% CI, 0.707–1.068).

Secondary endpoints further supported these findings:

• Overall Survival (OS): The median OS was 32.6 months (95% CI, 26.0–34.9) in the DHP107 group and 31.8 months (95% CI, 24.4–36.3) in the IV paclitaxel group (HR, 0.967; 95% CI, 0.762–1.227).
• Tumor Response: The investigator-assessed objective response rate (ORR) was 43.3% for DHP107 versus 38.8% for IV paclitaxel. The disease control rate (DCR) was 89.2% and 84.4%, respectively.
• Quality of Life (QoL): EQ-5D-3L index and EQ-VAS scores remained comparable between the two groups throughout the treatment cycles, showing no meaningful decline until the end of treatment.
• Time to Treatment Failure (TTF): The median TTF was 7.6 months for the oral group and 7.4 months for the IV group (HR, 0.875; 95% CI, 0.731–1.046).

Trial details

The OPTIMAL trial enrolled 549 patients who were randomized 1:1 to receive either DHP107 (n=277) or IV paclitaxel (n=272). Eligible participants were aged 19 years or older with histologically confirmed HER2-negative recurrent or metastatic breast cancer. Patients must not have received prior chemotherapy for metastatic disease, though prior taxane use in the (neo)adjuvant setting was permitted if completed at least one year before randomization.

Patients in the DHP107 group received 200 mg/m² orally twice daily on days 1, 8, and 15 of a 28-day cycle. Those in the IV group received 80 mg/m² intravenously on the same schedule. While premedication was mandatory for the IV group to prevent hypersensitivity reactions, it was not required for the DHP107 group. Randomization was stratified by disease-free interval, presence of visceral metastasis, and geographic region. The majority of the population was Asian (83.4%), with 16.2% Caucasian participants. The median age was 56 years, and 87.6% of patients had hormone receptor–positive disease.

Safety

Safety analyses included 540 patients who received at least one dose of study treatment. While treatment-emergent adverse events (TEAEs) occurred in nearly all patients (97.8% for DHP107 and 96.6% for IV paclitaxel), the specific toxicities differed between the two arms.

Grade 3 or higher TEAEs were more frequent in the DHP107 group (77.3% vs. 47.5%). This was primarily driven by higher rates of:

• Neutropenia: 81.6% in the DHP107 group (67.1% grade ≥3) vs. 59.3% in the IV group (29.7% grade ≥3).
• Febrile neutropenia: 6.1% in the DHP107 group vs. 0.8% in the IV group.
• Gastrointestinal events: Nausea (43.0% vs. 14.8%), diarrhea (38.3% vs. 11.0%), and vomiting (26.7% vs. 8.0%) were more common with oral administration but were predominantly grade 1 or 2.

Conversely, the IV paclitaxel group experienced higher rates of:

• Peripheral neuropathy: 48.3% vs. 37.9% in the DHP107 group.
• Hypersensitivity reactions: 2.7% vs. 0.7% in the DHP107 group.

Dose interruptions due to adverse events occurred in 63.5% of the DHP107 group compared to 38.4% in the IV group. There were no treatment-related deaths in the DHP107 group, while one treatment-related death (0.4%) occurred in the IV paclitaxel group. The mean relative dose intensity was 83.4% for DHP107 and 89.0% for IV paclitaxel.

Reference:

1. Kim SB, Xu B, Sun T, et al. Phase III trial of oral paclitaxel (DHP107) versus intravenous paclitaxel in HER2-negative recurrent or metastatic breast cancer: primary analysis of a multinational OPTIMAL trial. Ann Oncol. 2024;35(10):890-898. doi:10.1016/j.annonc.2024.06.007