Multinational phase 3 of oral paclitaxel versus intravenous weekly paclitaxel for HER2-negative recurrent or metastatic breast cancer

Intravenous (IV) paclitaxel requires prolonged infusion and in associated with hypersensitivity reactions and peripheral neuropathy. DHP107 is a novel oral formulation of paclitaxel. The phase 3 OPTIMAL trial, at 51 sites in South Korea, China, and Europe, enrolled 549 patients compared IV paclitaxel and DHP107 among patients with HER2-negative recurrent or metastatic breast cancer (R/M BC) who had received no prior chemotherapy in the metastatic setting. Patients were randomized to receive DHP107 200 mg/m² twice daily on days 1, 8, and 15 (n=277) or IV paclitaxel 80 mg/m² on days 1, 8 and 15 (n=272) of 28-day cycles. Treatment was continued until disease progression or unacceptable toxicity. Primary endpoint was investigator-assessed progression-free survival. At the data cutoff date, the median follow-up was 38.8 months in the DHP107 group and 39.0 months in the IV paclitaxel group. DHP107 was noninferior to IV paclitaxel for the endpoints progression-free survival and overall survival. DHP107 was associated with higher rates of neutropenia, febrile neutropenia, nausea, diarrhea, and vomiting, whereas peripheral neuropathy and hypersensitivity were more common with IV paclitaxel. Treatment-related death occurred in no patient in the DHP107 group and in one patient (0.4%) in the paclitaxel group. Quality of life was comparable between the two groups. The authors conclude that DHP107 demonstrated noninferior efficacy compared to IV paclitaxel, with a manageable safety profile, supporting its use in HER2-negative R/M BC.