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

Yoon Koo Kang, M. H. Ryu, S. H. Park, J. G. Kim, J. W. Kim, S. H. Cho, Y. I. Park, S. R. Park, S. Y. Rha, M. J. Kang, J. Y. Cho, S. Y. Kang, S. Y. Roh, B. Y. Ryoo, B. H. Nam, Y. W. Jo, K. E. Yoon, S. C. Oh

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Abstract

Background: Paclitaxel is currently only available as an intravenous (i.v.) formulation. DHP107 is a novel oral formulation of lipid ingredients and paclitaxel. DHP107 demonstrated comparable efficacy, safety, and pharmacokinetics to i.v. paclitaxel as a secondline 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 i.v. 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 end point: non-inferiority of progression-free survival (PFS); secondary end points: overall response rate (ORR), overall survival (OS), and safety. For the efficacy analysis, sequential tests for non-inferiority were carried out, 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 (full 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. There were only few Grade≥3 adverse events, most commonly neutropenia (42% versus 53%); febrile neutropenia was reported infrequently (5.9% versus 2.5%). No hypersensitivity reactions occurred with DHP107 (paclitaxel 2.5%). Conclusions: DHP107 as a second-line treatment of 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.

Original languageEnglish
Pages (from-to)1220-1226
Number of pages7
JournalAnnals of Oncology
Volume29
Issue number5
DOIs
Publication statusPublished - 2018 May 1

All Science Journal Classification (ASJC) codes

  • Hematology
  • Oncology

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    Kang, Y. K., Ryu, M. H., Park, S. H., Kim, J. G., Kim, J. W., Cho, S. H., Park, Y. I., Park, S. R., Rha, S. Y., Kang, M. J., Cho, J. Y., Kang, S. Y., Roh, S. Y., Ryoo, B. Y., Nam, B. H., Jo, Y. W., Yoon, K. E., & Oh, S. C. (2018). Efficacy and safety findings from DREAM: A phase III study of DHP107 (oral paclitaxel) versus i.v. paclitaxel in patients with advanced gastric cancer after failure of first-line chemotherapy. Annals of Oncology, 29(5), 1220-1226. https://doi.org/10.1093/annonc/mdy055