Efficacy and safety findings from DREAM: a phase III study of DHP107 (oral paclitaxel) versus IV paclitaxel in patients with advanced gastric cancer after failure of first-line chemotherapy

Abstract

Background

Paclitaxel is currently only available as an intravenous (IV) formulation. DHP107 is a novel oral formulation of lipid ingredients and paclitaxel. DHP107 demonstrated comparable efficacy, safety, and pharmacokinetics to IV paclitaxel as second-line therapy in patients with advanced gastric cancer (AGC). DREAM is a multicenter, open-label, prospective, randomized phase III study of patients with histologically/cytologically confirmed, unresectable/recurrent AGC after first-line therapy failure.

Methods and materials

Patients were randomized 1:1 to DHP107 (200 mg/m² orally twice daily days 1, 8, 15 every 4 weeks) or IV paclitaxel (175 mg/m² day 1 every 3 weeks). Patients were stratified by Eastern Cooperative Oncology Group performance status, disease status, and prior treatment; response was assessed (Response Evaluation Criteria in Solid Tumors) every 6 weeks. Primary endpoint: non-inferiority of progression-free survival (PFS); secondary endpoints: overall response rate (ORR), overall survival (OS), and safety. For the efficacy analysis, sequential tests for non-inferiority were performed, first with a non-inferiority margin of 1.48, then with a margin of 1.25.

Results

Baseline characteristics were balanced in the 236 randomized patients (n=118 per arm). Median PFS (per-protocol) was 3.0 (95% CI, 1.7-4.0) months for DHP107 and 2.6 (95% CI, 1.8-2.8) months for paclitaxel (hazard ratio [HR]=0.85; 95% CI, 0.64-1.13). A sensitivity analysis on PFS using independent central review showed similar results (HR = 0.93; 95% CI, 0.70-1.24). Median OS (final analysis set) was 9.7 (95% CI, 7.1-11.5) months for DHP107 versus 8.9 (95% CI, 7.1-12.2) months for paclitaxel (HR = 1.04; 95% CI, 0.76-1.41). ORR was 17.8% for DHP107 (CR 4.2%; PR 13.6%) versus 25.4% for paclitaxel (CR 3.4%; PR 22.0%). Nausea, vomiting, diarrhea, and mucositis were more common with DHP107; peripheral neuropathy was more common with paclitaxel. Grade ≥3 adverse events were infrequent, most commonly neutropenia (42% versus 53%); febrile neutropenia was rare (5.9% versus 2.5%). No hypersensitivity reactions occurred with DHP107 (paclitaxel 2.5%).

Conclusions

DHP107 as second-line treatment for AGC was non-inferior to paclitaxel for PFS; other efficacy and safety parameters were comparable. DHP107 is the first oral paclitaxel with proven efficacy/safety for the treatment of AGC. ClinicalTrials.gov: NCT01839773.