4 research outputs found
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
IMPORTANCE Treatment with the anti-ERBB2 humanized monoclonal antibody trastuzumab
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.
OBJECTIVE To compare the overall response rate and assess the safety of a proposed
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 Among 500 women randomized, the intention-to-treat population included 458
women (mean [SD] age, 53.6 [11.11] years) and the safety population included 493 women.
The ORR was 69.6% (95% CI, 63.62%-75.51%) for the proposed biosimilar vs 64.0% (95% CI,
57.81%-70.26%) for trastuzumab. The ORR ratio (1.09; 90% CI, 0.974-1.211) and ORR difference
(5.53; 95% CI, −3.08 to 14.04) were within the equivalence boundaries. At week 48, there was no
statistically significant difference with the proposed biosimilar vs trastuzumab for time to tumor
progression (41.3% vs 43.0%; −1.7%; 95% CI, −11.1% to 6.9%), progression-free survival (44.3%
vs 44.7%; −0.4%; 95% CI, −9.4% to 8.7%), or overall survival (89.1% vs 85.1%; 4.0%; 95% CI,
−2.1% to 10.3%). In the proposed biosimilar and trastuzumab groups, 239 (98.6%) and 233
(94.7%) had at least 1 adverse event, the most common including neutropenia (57.5% vs 53.3%),
peripheral neuropathy (23.1% vs 24.8%), and diarrhea (20.6% vs 20.7%).
CONCLUSIONS AND RELEVANCE Among women with ERBB2-positive metastatic breast cancer
receiving taxanes, the use of a proposed trastuzumab biosimilar compared with trastuzumab
resulted in an equivalent overall response rate at 24 weeks. Further study is needed to assess
safety and long-term clinical outcome.
TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT02472964; EudraCT Identifier:
2011-001965-4
Practitioners section - Homocysteine in cardiovascular disease: A culprit or an innocent bystander?
Whether hyperhomocysteinemia is a cardiovascular risk factor or is just
an epiphenomenon is a subject of debate. More than 20 prospective and
30 retrospective studies on the topic have been published. Despite huge
literature available, an unequivocal view has not been firmly
established. Medical fraternity is still witnessing differing opinions
regarding need to treat hyperhomocysteinemia. A medical practitioner
needs to be well informed of developments and current opinion on this
subject as it has a strong bearing on a major emerging public health
problem of cardiovascular disease (CVD). This review presents the two
views - for and against the acceptance of association between
hyperhomocysteinemia and cardiovascular disease - and their basis. The
two views are examined in the light of clinical, epidemiologic and
genetic studies, reviews and meta-analyses available. Following
conclusion was drawn from the exercise: The available evidence
indicates that homocysteine is not an innocent bystander; it is an
independent risk factor for CVD. The need for homocysteine-lowering
therapy is however not yet unequivocally established. Physicians need
to be vigilant of the updates on this much-debated topic thrusted on
them time and again
A pharmacokinetics study of proposed bevacizumab biosimilar MYL-1402O vs EU-bevacizumab and US-bevacizumab
Purpose!#!Bevacizumab is a recombinant humanized monoclonal antibody that inhibits vascular endothelial growth factor-specific angiogenesis in some cancers. MYL-1402O is a proposed bevacizumab biosimilar.!##!Methods!#!The primary objective of this single-center, randomized, double-blind, three-arm, parallel-group, phase 1 study in healthy male volunteers was to evaluate bioequivalence of MYL-1402O to EU and US-reference bevacizumab, and EU-reference bevacizumab to US-reference bevacizumab. The primary pharmacokinetic parameter was area under the serum concentration-time curve from 0 extrapolated to infinity (AUC!##!Results!#!Of 111 enrolled subjects, 110 were included in the pharmacokinetic analysis (MYL-1402O, n = 37; EU-reference bevacizumab, n = 36; US-reference bevacizumab, n = 37). Bioequivalence was demonstrated between MYL-1402O and EU-reference bevacizumab, MYL-1402O and US-reference bevacizumab, and between EU- and US-reference bevacizumab where least squares mean ratios of AUC!##!Conclusion!#!MYL-1402O was well tolerated and demonstrated pharmacokinetic and safety profiles similar to EU-reference bevacizumab and US-reference bevacizumab in healthy male volunteers. No new significant safety issues emerged (ClinicalTrials.gov, NCT02469987; ClinicalTrialsRegister.eu EudraCT, 2014-005621-12; June 12, 2015)