OPTIMAL: a multinational phase III study of oral paclitaxel (DHP107) versus intravenous weekly paclitaxel in HER2-negative recurrent or metastatic breast cancer.

This study evaluated the efficacy and safety of DHP107, a novel oral formulation of paclitaxel, compared with i.v. paclitaxel in patients with HER2-negative, recurrent, or metastatic breast cancer.

本研究评估了DHP107（一种新型口服紫杉醇制剂）与静脉注射紫杉醇相比，在HER2阴性、复发性或转移性乳腺癌患者中的疗效和安全性。

patients_and_methods

This multinational, multicenter, open-label, randomized phase III trial evaluated the noninferiority of DHP107 compared with i.v. paclitaxel, with a predefined noninferiority margin of 1.33.

这项多国、多中心、开放标签、随机III期试验评估了DHP107与静脉注射紫杉醇相比的非劣效性，预设的非劣效性边界为1.33。

Eligible patients had recurrent or metastatic breast cancer and had received no prior chemotherapy in the metastatic setting.

符合条件的患者患有复发性或转移性乳腺癌，并且在转移性环境中未接受过化疗。

Patients were randomly assigned to receive either DHP107 (200 mg/m2 orally twice daily on days 1, 8, and 15) or paclitaxel (80 mg/m2 i.v. on days 1, 8, and 15) in a 28-day cycle.

患者被随机分配接受DHP107（口服，200 mg/m2，第1、8、15天，每日两次）或紫杉醇（静脉注射，80 mg/m2，第1、8、15天）治疗，每28天为一个周期。

The primary endpoint was investigator-assessed progression-free survival(PFS) in the per-protocol set (PPS).

主要终点是研究者评估的无进展生存期（PFS），在符合方案集（PPS）中进行评估。

Secondary endpoints included independent central review-assessed PFS, overall survival(OS), tumor response, quality of life, and safety.

次要终点包括独立中央审查评估的无进展生存期（PFS）、总生存（OS）、肿瘤反应、生活质量及安全性。

Results

Between January 2018 and December 2023, 549 patients were randomly assigned to receive either DHP107 (n = 277) or paclitaxel (n = 272); 519 patients were included in the PPS.

在2018年1月至2023年12月期间，共有549名患者被随机分配接受DHP107（n = 277）或紫杉醇（n = 272）治疗；共有519名患者被纳入意向治疗人群（PPS）。

DHP107 demonstrated noninferiority in PFS with a median PFS of 10.0 months compared with 8.5 months for paclitaxel (hazard ratio[HR] 0.869; 95% confidence interval[CI] 0.707-1.068).

DHP107在无进展生存期（PFS）上显示出非劣效性，中位PFS为10.0个月，而紫杉醇为8.5个月（风险比[HR] 0.869；95%置信区间[CI] 0.707-1.068）。

The median OS was 32.6 months for DHP107 and 31.8 months for paclitaxel (HR 0.967, 95% CI 0.762-1.227).

DHP107的总生存期（OS）中位数为32.6个月，紫杉醇为31.8个月（HR 0.967，95% CI 0.762-1.227）。

DHP107 was associated with higher rates of neutropenia, febrile neutropenia, nausea, diarrhea, and vomiting, whereas peripheral neuropathy and hypersensitivity reactions were more common with paclitaxel.

DHP107与较高的中性粒细胞减少症、发热性中性粒细胞减少症、恶心、腹泻和呕吐发生率相关，而外周神经病变和超敏反应在紫杉醇组更为常见。

No treatment-related death occurred in the DHP107 group, and one (0.4%) in the paclitaxel group.

DHP107组中没有发生与治疗相关的死亡，紫杉醇组中有一例（0.4%）发生。

Quality of life was comparable between the two groups.

两组的生活质量相当。

Conclusions

DHP107 demonstrated noninferior efficacy compared with i.v. paclitaxel, with a manageable safety profile, supporting its use as an effective and convenient alternative in HER2-negative breast cancer.

DHP107展现了与静脉注射紫杉醇相当的非劣效性疗效，具有可管理的安全性特征，支持其作为HER2阴性乳腺癌有效且方便的替代治疗方案。