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Research

JAMA | Original Investigation
บทความตีพิมพ์ข้อมูลของผู้ป่วยซึ่งทางศูนย์ฯ ได้ร่วมในการทำาการวิจัย MYLAN JAMA
Effect of a Proposed Trastuzumab Biosimilar Compared

With Trastuzumab on Overall Response Rate in Patients
With ERBB2 (HER2)–Positive Metastatic Breast Cancer

A Randomized Clinical Trial

Hope S. Rugo, MD; Abhijit Barve, MD, PhD, MBA; Cornelius F. Waller, MD; Miguel Hernandez-Bronchud, MD, PhD; Jay Herson, PhD; Jinyu Yuan, PhD;
Rajiv Sharma, MBBS, MS; Mark Baczkowski, MS, RPh; Mudgal Kothekar, MD; Subramanian Loganathan, MD; Alexey Manikhas, MD; Igor Bondarenko, MD;
Guzel Mukhametshina, MD; Gia Nemsadze, MD, PhD; Joseph D. Parra, MD; Maria Luisa T. Abesamis-Tiambeng, MD; Kakhaber Baramidze, MD, PhD;
Charuwan Akewanlop, MD; Ihor Vynnychenko, MD; Virote Sriuranpong, MD; Gopichand Mamillapalli, MS, MCh; Sirshendu Ray, MS;
Eduardo P. Yanez Ruiz, MD; Eduardo Pennella, MD, MBA; for the Heritage Study Investigators

Editorial pages 30 and 33
IMPORTANCE Treatment with the anti-ERBB2 humanized monoclonal antibody trastuzumab Supplemental content
and chemotherapy significantly improves outcome in patients with ERBB2 (HER2)–positive
metastatic breast cancer; a clinically effective biosimilar may help increase access to this therapy. CME Quiz at
jamanetworkcme.com and
OBJECTIVE To compare the overall response rate and assess the safety of a proposed CME Questions page 83
trastuzumab biosimilar plus a taxane or trastuzumab plus a taxane in patients without prior
treatment for ERBB2-positive metastatic breast cancer.

DESIGN, SETTING, AND PARTICIPANTS Multicenter, double-blind, randomized, parallel-group,
phase 3 equivalence study in patients with metastatic breast cancer. From December 2012 to
August 2015, 500 patients were randomized 1:1 to receive a proposed biosimilar or
trastuzumab plus a taxane. Chemotherapy was administered for at least 24 weeks followed
by antibody alone until unacceptable toxic effects or disease progression occurred.

INTERVENTIONS Proposed biosimilar (n = 230) or trastuzumab (n = 228) with a taxane.
MAIN OUTCOMES AND MEASURES The primary outcome was week 24 overall response rate
(ORR) defined as complete or partial response. Equivalence boundaries were 0.81 to 1.24
with a 90% CI for ORR ratio (proposed biosimilar/trastuzumab) and −15% to 15% with a 95%
CI for ORR difference. Secondary outcome measures included time to tumor progression,
progression-free and overall survival at week 48, and adverse events.

RESULTS Among500womenrandomized,theintention-to-treatpopulationincluded458
women(mean[SD]age,53.6[11.11]years)andthesafetypopulationincluded493women.
TheORRwas69.6%(95%CI,63.62%-75.51%)fortheproposedbiosimilarvs64.0%(95%CI,
57.81%-70.26%)fortrastuzumab.TheORRratio(1.09;90%CI,0.974-1.211)andORRdifference
(5.53;95%CI,−3.08to14.04)werewithintheequivalenceboundaries.Atweek48,therewasno
statisticallysignificantdifferencewiththeproposedbiosimilarvstrastuzumabfortimetotumor
progression(41.3%vs43.0%;−1.7%;95%CI,−11.1%to6.9%),progression-freesurvival(44.3%
vs44.7%;−0.4%;95%CI,−9.4%to8.7%),oroverallsurvival(89.1%vs85.1%;4.0%;95%CI,
−2.1%to10.3%).Intheproposedbiosimilarandtrastuzumabgroups,239(98.6%)and233
(94.7%)hadatleast1adverseevent,themostcommonincludingneutropenia(57.5%vs53.3%),
peripheralneuropathy(23.1%vs24.8%),anddiarrhea(20.6%vs20.7%). Author Affiliations: Author
affiliations are listed at the end of this
CONCLUSIONS AND RELEVANCE Among women with ERBB2-positive metastatic breast cancer article.
receiving taxanes, the use of a proposed trastuzumab biosimilar compared with trastuzumab Group Information: A complete list
resulted in an equivalent overall response rate at 24 weeks. Further study is needed to assess of the Heritage Study Investigators
safety and long-term clinical outcome. is provided in the eAppendix
in Supplement 1.
TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT02472964; EudraCT Identifier: Corresponding Author: Hope S.
Rugo, MD, University of California
2011-001965-42 San Francisco Helen Diller Family
Comprehensive Cancer Center, 1600
JAMA. 2017;317(1):37-47. doi:10.1001/jama.2016.18305 Divisadero St, San Francisco, CA
Published online December 1, 2016. 94127 (hope.rugo@ucsf.edu).

(Reprinted) 37
Copyright 2017 American Medical Association. All rights reserved.
Copyright 2017 American Medical Association. All rights reserved.
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