BATON-CRC: A Phase II Randomized Trial Comparing Tivozanib Plus mFOLFOX6 with Bevacizumab Plus mFOLFOX6 in Stage IV Metastatic Colorectal Cancer

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00209805%3A_____%2F16%3AN0000053" target="_blank" >RIV/00209805:_____/16:N0000053 - isvavai.cz</a>

Výsledek na webu

<a href="http://clincancerres.aacrjournals.org/content/early/2016/07/09/1078-0432.CCR-15-3117" target="_blank" >http://clincancerres.aacrjournals.org/content/early/2016/07/09/1078-0432.CCR-15-3117</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1158/1078-0432.CCR-15-3117" target="_blank" >10.1158/1078-0432.CCR-15-3117</a>

Jazyk výsledku

angličtina

Název v původním jazyce

BATON-CRC: A Phase II Randomized Trial Comparing Tivozanib Plus mFOLFOX6 with Bevacizumab Plus mFOLFOX6 in Stage IV Metastatic Colorectal Cancer

Popis výsledku v původním jazyce

Purpose: Tivozanib, a selective inhibitor of VEGFR-1, -2, and -3, plus mFOLFOX6 in an advanced gastrointestinal cancer phase Ib study had encouraging antineoplastic activity and a tolerable safety profile. This randomized, open-label, phase II trial of tivozanib/mFOLFOX6 versus bevacizumab/mFOLFOX6 in patients with previously untreated metastatic colorectal cancer (mCRC) evaluated tivozanib activity versus bevacizumab. Experimental Design: Treatment-naïve patients received mFOLFOX6 every 2 weeks of each 28-day cycle plus either tivozanib orally 1.5 mg once daily for 21 days or bevacizumab intravenously 5 mg/kg every 2 weeks. Investigator-assessed PFS was the primary endpoint; some secondary endpoints included safety, overall survival, ORR, duration of response, time to treatment failure, and biomarker subgroup analyses. Results: A prespecified interim futility analysis demonstrated that the futility boundary for superiority of tivozanib/mFOLFOX6 over bevacizumab/mFOLFOX6 for PFS in the intent-to-treat population was crossed; median PFS was 9.4 versus 10.7 months [HR ¼ 1.091; confidence interval (CI), 0.693–1.718; P ¼ 0.706]. Tivozanib/mFOLFOX6 resulted in PFS and ORR comparable with bevacizumab/mFOLFOX6; interim analyses biomarker results revealed no significant PFS association. Post hoc final analyses demonstrated a potential difference in tivozanib-specific PFS in patients with low neuropilin-1 (NRP-1), but not in patients with high NRP-1. Conclusions: The efficacy of tivozanib/mFOLFOX6 was comparable with but not superior to bevacizumab/mFOLFOX6 in patients with previously untreated mCRC. Since data from the prespecified interim analysis did not demonstrate superiority, this resulted in discontinuation of the study. The safety and tolerability profile of tivozanib/mFOLFOX6 was consistent with other tivozanib trials. NRP-1 is a potential predictive biomarker for tivozanib activity, but these results require further validation.

Název v anglickém jazyce

BATON-CRC: A Phase II Randomized Trial Comparing Tivozanib Plus mFOLFOX6 with Bevacizumab Plus mFOLFOX6 in Stage IV Metastatic Colorectal Cancer

Popis výsledku anglicky

Purpose: Tivozanib, a selective inhibitor of VEGFR-1, -2, and -3, plus mFOLFOX6 in an advanced gastrointestinal cancer phase Ib study had encouraging antineoplastic activity and a tolerable safety profile. This randomized, open-label, phase II trial of tivozanib/mFOLFOX6 versus bevacizumab/mFOLFOX6 in patients with previously untreated metastatic colorectal cancer (mCRC) evaluated tivozanib activity versus bevacizumab. Experimental Design: Treatment-naïve patients received mFOLFOX6 every 2 weeks of each 28-day cycle plus either tivozanib orally 1.5 mg once daily for 21 days or bevacizumab intravenously 5 mg/kg every 2 weeks. Investigator-assessed PFS was the primary endpoint; some secondary endpoints included safety, overall survival, ORR, duration of response, time to treatment failure, and biomarker subgroup analyses. Results: A prespecified interim futility analysis demonstrated that the futility boundary for superiority of tivozanib/mFOLFOX6 over bevacizumab/mFOLFOX6 for PFS in the intent-to-treat population was crossed; median PFS was 9.4 versus 10.7 months [HR ¼ 1.091; confidence interval (CI), 0.693–1.718; P ¼ 0.706]. Tivozanib/mFOLFOX6 resulted in PFS and ORR comparable with bevacizumab/mFOLFOX6; interim analyses biomarker results revealed no significant PFS association. Post hoc final analyses demonstrated a potential difference in tivozanib-specific PFS in patients with low neuropilin-1 (NRP-1), but not in patients with high NRP-1. Conclusions: The efficacy of tivozanib/mFOLFOX6 was comparable with but not superior to bevacizumab/mFOLFOX6 in patients with previously untreated mCRC. Since data from the prespecified interim analysis did not demonstrate superiority, this resulted in discontinuation of the study. The safety and tolerability profile of tivozanib/mFOLFOX6 was consistent with other tivozanib trials. NRP-1 is a potential predictive biomarker for tivozanib activity, but these results require further validation.

Druh

J_x - Nezařazeno - Článek v odborném periodiku (Jimp, Jsc a Jost)

CEP obor

FD - Onkologie a hematologie

OECD FORD obor

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Projekt

—

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2016

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Clinical cancer research

ISSN

1078-0432

e-ISSN

—

Svazek periodika

22

Číslo periodika v rámci svazku

20

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

10

Strana od-do

5058-5067

Kód UT WoS článku

000385632700014

EID výsledku v databázi Scopus

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