Frontline bortezomib, rituximab, cyclophosphamide, doxorubicin,
and prednisone (VR-CAP) versus rituximab, cyclophosphamide,
doxorubicin, vincristine, and prednisone (R-CHOP) in
transplantation-ineligible patients with newly diagnosed mantle
cell lymphoma: final overall survival results of a randomised,
open-label, phase 3 study

J 2018

Frontline bortezomib, rituximab, cyclophosphamide, doxorubicin, and prednisone (VR-CAP) versus rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) in transplantation-ineligible patients with newly diagnosed mantle cell lymphoma: final overall survival results of a randomised, open-label, phase 3 study

ROBAK, Tadeusz, Jie JIN, Halyna PYLYPENKO, Gregor VERHOEF, Noppadol SIRITANARATKUL et. al.

Basic information

Original name

Frontline bortezomib, rituximab, cyclophosphamide, doxorubicin, and prednisone (VR-CAP) versus rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) in transplantation-ineligible patients with newly diagnosed mantle cell lymphoma: final overall survival results of a randomised, open-label, phase 3 study

Authors

ROBAK, Tadeusz (616 Poland, guarantor), Jie JIN (156 China), Halyna PYLYPENKO (804 Ukraine), Gregor VERHOEF (56 Belgium), Noppadol SIRITANARATKUL (764 Thailand), Johannes DRACH (40 Austria), Markus RADERER (40 Austria), Jiří MAYER (203 Czech Republic, belonging to the institution), Juliana PEREIRA (76 Brazil), Gayane TUMYAN (643 Russian Federation), Rumiko OKAMOTO (392 Japan), Susumu NAKAHARA (392 Japan), Peter HU (840 United States of America), Carlos APPIANI (840 United States of America), Sepideh NEMAT (826 United Kingdom of Great Britain and Northern Ireland) and Franco CAVALLI (756 Switzerland)

Edition

Lancet Oncology, New York, Elsevier Science INC, 2018, 1470-2045

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

30204 Oncology

Country of publisher

United States of America

Confidentiality degree

není předmětem státního či obchodního tajemství

Impact factor

Impact factor: 35.386

RIV identification code

RIV/00216224:14110/18:00105320

Organization unit

Faculty of Medicine

DOI

http://dx.doi.org/10.1016/S1470-2045(18)30685-5

UT WoS

000449100300042

Keywords in English

bortezomib; rituximab; cyclophosphamide; doxorubicin; prednisone

Abstract

V originále

Background In the LYM-3002 study, the efficacy and safety of frontline bortezomib plus rituximab, cyclophosphamide, doxorubicin, and prednisone (VR-CAP) and rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) were compared in transplant-ineligible patients with untreated, newly diagnosed, mantle cell lymphoma. We report the final overall survival and safety outcomes for patients in the long-term follow-up phase after the primary progression-free-survival endpoint was met. Methods LYM-3002 was a randomised, open-label, phase 3 study done at 128 clinical centres in 28 countries in Asia, Europe, North America, and South America. Adult patients with confirmed stage II-IV previously untreated mantle cell lymphoma, Eastern Cooperative Oncology Group performance status score of 2 or less, who were ineligible for bone marrow transplantation, were randomly assigned (1: 1) to receive six or eight 21-day cycles of VR-CAP (intravenous rituximab 375 mg/m(2), cyclophosphamide 750 mg/m(2), doxorubicin 50 mg/m(2), and bortezomib 1.3 mg/m(2), plus oral prednisone 100 mg/m(2)) or R-CHOP (intravenous vincristine 1.4 mg/m(2) [2 mg maximum], rituximab 375 mg/m(2), cyclophosphamide 750 mg/m(2), and doxorubicin 50 mg/m(2), plus oral prednisone 100 mg/m(2)). Randomisation was done according to a computer-generated randomisation schedule prepared by the sponsor; permuted blocks central randomisation was used (block size of 4), and was stratified by International Prognostic Index score and disease stage at diagnosis. The primary endpoint of this final analysis was overall survival, which was analysed in the intention-totreat population. This study is registered with ClinicalTrials.gov, number NCT00722137, and is closed to new participants with follow-up completed. Findings Between May 22, 2008, and Dec 5, 2011, 487 patients were enrolled and randomly assigned. 268 patients (140 in the VR-CAP group and 128 in the R-CHOP group) were included in the follow-up analysis, which included patients with data available after the primary analysis clinical cutoff date of Dec 2, 2013. After median follow-up of 82.0 months (IQR 74.1-94.2), median overall survival was significantly longer in the VR-CAP group than in the R-CHOP group (90.7 months [95% CI 71.4 to not estimable] vs 55.7 months [47.2 to 68.9]; hazard ratio 0.66 [95% CI 0.51-0.85]; p=0.001). Three new adverse events were reported since the primary analysis cutoff (one each of grade 4 lung adenocarcinoma and grade 4 gastric cancer in the VR-CAP group, and one case of grade 2 pneumonia in the R-CHOP group). 103 (42%) of 243 patients in the VR-CAP group, and 138 (57%) of 244 in the R-CHOP group died; the most common cause of death was progressive disease. Interpretations Compared with R-CHOP, VR-CAP was associated with significantly longer survival, and had a manageable and expected safety profile. Our results support further assessment of VR-CAP in patients with previously untreated mantle cell lymphoma. Copyright (C) 2018 Elsevier Ltd. All rights reserved.

Citovat

ROBAK, Tadeusz, Jie JIN, Halyna PYLYPENKO, Gregor VERHOEF, Noppadol SIRITANARATKUL, Johannes DRACH, Markus RADERER, Jiří MAYER, Juliana PEREIRA, Gayane TUMYAN, Rumiko OKAMOTO, Susumu NAKAHARA, Peter HU, Carlos APPIANI, Sepideh NEMAT and Franco CAVALLI. Frontline bortezomib, rituximab, cyclophosphamide, doxorubicin, and prednisone (VR-CAP) versus rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) in transplantation-ineligible patients with newly diagnosed mantle cell lymphoma: final overall survival results of a randomised, open-label, phase 3 study. Lancet Oncology. New York: Elsevier Science INC, 2018, vol. 19, No 11, p. 1449-1458. ISSN 1470-2045. Available from: https://dx.doi.org/10.1016/S1470-2045(18)30685-5.

@article{1484272,
   author = {Robak, Tadeusz and Jin, Jie and Pylypenko, Halyna and Verhoef, Gregor and Siritanaratkul, Noppadol and Drach, Johannes and Raderer, Markus and Mayer, Jiří and Pereira, Juliana and Tumyan, Gayane and Okamoto, Rumiko and Nakahara, Susumu and Hu, Peter and Appiani, Carlos and Nemat, Sepideh and Cavalli, Franco},
   article_location = {New York},
   article_number = {11},
   doi = {http://dx.doi.org/10.1016/S1470-2045(18)30685-5},
   keywords = {bortezomib; rituximab; cyclophosphamide; doxorubicin; prednisone},
   language = {eng},
   issn = {1470-2045},
   journal = {Lancet Oncology},
   title = {Frontline bortezomib, rituximab, cyclophosphamide, doxorubicin, and prednisone (VR-CAP) versus rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) in transplantation-ineligible patients with newly diagnosed mantle cell lymphoma: final overall survival results of a randomised, open-label, phase 3 study},
   volume = {19},
   year = {2018}
}

TY  - JOUR
ID  - 1484272
AU  - Robak, Tadeusz - Jin, Jie - Pylypenko, Halyna - Verhoef, Gregor - Siritanaratkul, Noppadol - Drach, Johannes - Raderer, Markus - Mayer, Jiří - Pereira, Juliana - Tumyan, Gayane - Okamoto, Rumiko - Nakahara, Susumu - Hu, Peter - Appiani, Carlos - Nemat, Sepideh - Cavalli, Franco
PY  - 2018
TI  - Frontline bortezomib, rituximab, cyclophosphamide, doxorubicin, and prednisone (VR-CAP) versus rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) in transplantation-ineligible patients with newly diagnosed mantle cell lymphoma: final overall survival results of a randomised, open-label, phase 3 study
JF  - Lancet Oncology
VL  - 19
IS  - 11
SP  - 1449-1458
EP  - 1449-1458
PB  - Elsevier Science INC
SN  - 14702045
KW  - bortezomib
KW  - rituximab
KW  - cyclophosphamide
KW  - doxorubicin
KW  - prednisone
N2  - Background In the LYM-3002 study, the efficacy and safety of frontline bortezomib plus rituximab, cyclophosphamide, doxorubicin, and prednisone (VR-CAP) and rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) were compared in transplant-ineligible patients with untreated, newly diagnosed, mantle cell lymphoma. We report the final overall survival and safety outcomes for patients in the long-term follow-up phase after the primary progression-free-survival endpoint was met. Methods LYM-3002 was a randomised, open-label, phase 3 study done at 128 clinical centres in 28 countries in Asia, Europe, North America, and South America. Adult patients with confirmed stage II-IV previously untreated mantle cell lymphoma, Eastern Cooperative Oncology Group performance status score of 2 or less, who were ineligible for bone marrow transplantation, were randomly assigned (1: 1) to receive six or eight 21-day cycles of VR-CAP (intravenous rituximab 375 mg/m(2), cyclophosphamide 750 mg/m(2), doxorubicin 50 mg/m(2), and bortezomib 1.3 mg/m(2), plus oral prednisone 100 mg/m(2)) or R-CHOP (intravenous vincristine 1.4 mg/m(2) [2 mg maximum], rituximab 375 mg/m(2), cyclophosphamide 750 mg/m(2), and doxorubicin 50 mg/m(2), plus oral prednisone 100 mg/m(2)). Randomisation was done according to a computer-generated randomisation schedule prepared by the sponsor; permuted blocks central randomisation was used (block size of 4), and was stratified by International Prognostic Index score and disease stage at diagnosis. The primary endpoint of this final analysis was overall survival, which was analysed in the intention-totreat population. This study is registered with ClinicalTrials.gov, number NCT00722137, and is closed to new participants with follow-up completed. Findings Between May 22, 2008, and Dec 5, 2011, 487 patients were enrolled and randomly assigned. 268 patients (140 in the VR-CAP group and 128 in the R-CHOP group) were included in the follow-up analysis, which included patients with data available after the primary analysis clinical cutoff date of Dec 2, 2013. After median follow-up of 82.0 months (IQR 74.1-94.2), median overall survival was significantly longer in the VR-CAP group than in the R-CHOP group (90.7 months [95% CI 71.4 to not estimable] vs 55.7 months [47.2 to 68.9]; hazard ratio 0.66 [95% CI 0.51-0.85]; p=0.001). Three new adverse events were reported since the primary analysis cutoff (one each of grade 4 lung adenocarcinoma and grade 4 gastric cancer in the VR-CAP group, and one case of grade 2 pneumonia in the R-CHOP group). 103 (42%) of 243 patients in the VR-CAP group, and 138 (57%) of 244 in the R-CHOP group died; the most common cause of death was progressive disease. Interpretations Compared with R-CHOP, VR-CAP was associated with significantly longer survival, and had a manageable and expected safety profile. Our results support further assessment of VR-CAP in patients with previously untreated mantle cell lymphoma. Copyright (C) 2018 Elsevier Ltd. All rights reserved.
ER  -

ROBAK, Tadeusz, Jie JIN, Halyna PYLYPENKO, Gregor VERHOEF, Noppadol SIRITANARATKUL, Johannes DRACH, Markus RADERER, Jiří MAYER, Juliana PEREIRA, Gayane TUMYAN, Rumiko OKAMOTO, Susumu NAKAHARA, Peter HU, Carlos APPIANI, Sepideh NEMAT and Franco CAVALLI. Frontline bortezomib, rituximab, cyclophosphamide, doxorubicin, and prednisone (VR-CAP) versus rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) in transplantation-ineligible patients with newly diagnosed mantle cell lymphoma: final overall survival results of a randomised, open-label, phase 3 study. \textit{Lancet Oncology}. New York: Elsevier Science INC, 2018, vol.~19, No~11, p.~1449-1458. ISSN~1470-2045. Available from: https://dx.doi.org/10.1016/S1470-2045(18)30685-5.

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