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

doi:10.1093/annonc/mdy055

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

Research output: Contribution to journal › Article › peer-review

42 Citations (Scopus)

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 language	English
Pages (from-to)	1220-1226
Number of pages	7
Journal	Annals of Oncology
Volume	29
Issue number	5
DOIs	https://doi.org/10.1093/annonc/mdy055
Publication status	Published - 2018 May 1

Bibliographical note

Funding Information:
The DREAM study was sponsored by Daehwa Pharmaceutical Co., Ltd (no grant number applies), Daehwa Building, 2145, Nambusunhwan-ro, Seocho-gu, Seoul, Korea. This work was supported by the Industrial Core Technology Development Program (10044732, The Development of New Oral Taxane Formulation for Breast and Gastrointestinal Cancer Using Solubilization Technology), which was funded by the Ministry of Trade, Industry and Energy (MOTIE, Korea) (no grant number applies).

Funding Information:
Third-party medical writing assistance was provided by Miller Medical Communications Ltd (funded by Daehwa Pharmaceutical Co., Ltd.).

Publisher Copyright:
© The Author(s) 2018. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved.

Keywords

DHP107
Gastric cancer
Non-inferiority
Oral paclitaxel
Progression free survival

ASJC Scopus subject areas

Hematology
Oncology

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1093/annonc/mdy055

Cite this

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

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. / Kang, Yoon Koo; Ryu, M. H.; Park, S. H. et al.
In: Annals of Oncology, Vol. 29, No. 5, 01.05.2018, p. 1220-1226.

Research output: Contribution to journal › Article › peer-review

Kang, YK, Ryu, MH, Park, SH, Kim, JG, Kim, JW, Cho, SH, Park, YI, Park, SR, Rha, SY, Kang, MJ, Cho, JY, Kang, SY, Roh, SY, Ryoo, BY, Nam, BH, Jo, YW, Yoon, KE & Oh, SC 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, vol. 29, no. 5, pp. 1220-1226. https://doi.org/10.1093/annonc/mdy055

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title = "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",

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.",

keywords = "DHP107, Gastric cancer, Non-inferiority, Oral paclitaxel, Progression free survival",

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

note = "Funding Information: The DREAM study was sponsored by Daehwa Pharmaceutical Co., Ltd (no grant number applies), Daehwa Building, 2145, Nambusunhwan-ro, Seocho-gu, Seoul, Korea. This work was supported by the Industrial Core Technology Development Program (10044732, The Development of New Oral Taxane Formulation for Breast and Gastrointestinal Cancer Using Solubilization Technology), which was funded by the Ministry of Trade, Industry and Energy (MOTIE, Korea) (no grant number applies). Funding Information: Third-party medical writing assistance was provided by Miller Medical Communications Ltd (funded by Daehwa Pharmaceutical Co., Ltd.). Publisher Copyright: {\textcopyright} The Author(s) 2018. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved.",

year = "2018",

month = may,

day = "1",

doi = "10.1093/annonc/mdy055",

language = "English",

volume = "29",

pages = "1220--1226",

journal = "Annals of Oncology",

issn = "0923-7534",

publisher = "Elsevier Ltd",

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TY - JOUR

T1 - Efficacy and safety findings from DREAM

T2 - A phase III study of DHP107 (oral paclitaxel) versus i.v. paclitaxel in patients with advanced gastric cancer after failure of first-line chemotherapy

AU - Kang, Yoon Koo

AU - Ryu, M. H.

AU - Park, S. H.

AU - Kim, J. G.

AU - Kim, J. W.

AU - Cho, S. H.

AU - Park, Y. I.

AU - Park, S. R.

AU - Rha, S. Y.

AU - Kang, M. J.

AU - Cho, J. Y.

AU - Kang, S. Y.

AU - Roh, S. Y.

AU - Ryoo, B. Y.

AU - Nam, B. H.

AU - Jo, Y. W.

AU - Yoon, K. E.

AU - Oh, S. C.

N1 - Funding Information: The DREAM study was sponsored by Daehwa Pharmaceutical Co., Ltd (no grant number applies), Daehwa Building, 2145, Nambusunhwan-ro, Seocho-gu, Seoul, Korea. This work was supported by the Industrial Core Technology Development Program (10044732, The Development of New Oral Taxane Formulation for Breast and Gastrointestinal Cancer Using Solubilization Technology), which was funded by the Ministry of Trade, Industry and Energy (MOTIE, Korea) (no grant number applies). Funding Information: Third-party medical writing assistance was provided by Miller Medical Communications Ltd (funded by Daehwa Pharmaceutical Co., Ltd.). Publisher Copyright: © The Author(s) 2018. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved.

PY - 2018/5/1

Y1 - 2018/5/1

N2 - 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.

AB - 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.

KW - DHP107

KW - Gastric cancer

KW - Non-inferiority

KW - Oral paclitaxel

KW - Progression free survival

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DO - 10.1093/annonc/mdy055

M3 - Article

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SN - 0923-7534

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JO - Annals of Oncology

JF - Annals of Oncology

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ER -

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

Abstract

Bibliographical note

Keywords

ASJC Scopus subject areas

UN SDGs

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