Journal article
Trebananib or placebo plus carboplatin and paclitaxel as first-line treatment for advanced ovarian cancer (TRINOVA-3/ENGOT-ov2/GOG-3001): a randomised, double-blind, phase 3 trial
The lancet oncology, Vol.20(6), pp.862-876
06/01/2019
DOI: 10.1016/S1470-2045(19)30178-0
PMID: 31076365
Abstract
Background Angiopoietin 1 and 2 regulate angiogenesis and vascular remodelling by interacting with the tyrosine kinase receptor Tie2, and inhibition of angiogenesis has shown promise in the treatment of ovarian cancer. We aimed to assess whether trebananib, a peptibody that inhibits binding of angiopoietin 1 and 2 to Tie2, improved progression-free survival when added to carboplatin and paclitaxel as first-line therapy in advanced epithelial ovarian, primary fallopian tube, or peritoneal cancer in a phase 3 clinical trial.
Methods TRINOVA-3, a multicentre, multinational, phase 3, double-blind study, was done at 206 investigational sites (hospitals and cancer centres) in 14 countries. Eligible patients were aged 18 years or older with biopsy-confirmed International Federation of Gynecology and Obstetrics (FIGO) stage III to IV epithelial ovarian, primary peritoneal, or fallopian tube cancers, and an ECOG performance status of 0 or 1. Eligible patients were randomly assigned (2:1) using a permuted block method (block size of six patients) to receive six cycles of paclitaxel (175 mg/m(2)) and carboplatin (area under the serum concentration-time curve 5 or 6) every 3 weeks, plus weekly intravenous trebananib 15 mg/kg or placebo. Maintenance therapy with trebananib or placebo continued for u p to 18 additional months. The primary endpoint was progression-free survival, as assessed by the investigators, in the intention-to-treat population. Safety analyses induded patients who received at least one dose of study treatment. This trial is registered with ClinicalTrials. gov , number NCT01493505, and is complete.
Findings Between Jan 30,2012, and Feb 25,2014,1164 patients were screened and 1015 eligible patients were randomly allocated to treatment (678 to trebananib and 337 to placebo). After a median follow-up of 27.4 months (IQR 17.7-34.2), 626 patients had progression-free survival events (405 [60%] of 678 in the trebananib group and 221 [66%] of 337 in the placebo group). Median progression-free survival did not differ between the trebananib group (15.9 months [15.0-17.6]) and the placebo group (15.0 months [12.6-16.1]) groups (hazard ratio 0.93 [95% CI 0.79-1.09]; p=0.36). 512 (76%) of 675 patients in the trebananib group and 237 (71%) of 336 in the placebo group had grade 3 or worse treatment-emergent adverse events; of which the most common events were neutropenia (trebananib 238 [35%] vs placebo 126 [38%]) anaemia (76 [11%] vs 40 [12%]), and leucopenia (81 [12%] vs 35 [10%]). 269 (40%) patients in the trebananib group and 104 (31%) in the placebo group had serious adverse events. Two fatal adverse events in the trebananib group were considered related to trebananib, paclitaxel, and carboplatin (lung infection and neutropenic colitis); two were considered to be related to paclitaxel and carboplatin (general physical health deterioration and platelet count decreased). No treatment-related fatal adverse events occurred in the placebo group.
Interpretation Trebananib plus carboplatin and paclitaxel did not improve progression-free survival as first-line treatment for advanced ovarian cancer. The combination of trebananib plus carboplatin and paclitaxel did not produce new safety signals. These results show that trebananib in combination with carboplatin and paclitaxel is minimally effective in this patient population. Copyright (C) 2019 Elsevier Ltd. All rights reserved.
Details
- Title: Subtitle
- Trebananib or placebo plus carboplatin and paclitaxel as first-line treatment for advanced ovarian cancer (TRINOVA-3/ENGOT-ov2/GOG-3001): a randomised, double-blind, phase 3 trial
- Creators
- Ignace Vergote - Belgium & Luxembourg Gynaecol Oncol Grp BGOG, Leuven, BelgiumGiovanni Scambia - Multictr Italian Trials Ovarian Canc Soc MITO, Rome, ItalyDavid M. O'Malley - Ohio State Univ, James Comprehens Canc Ctr, Gynecol Oncol Grp, Columbus, OH 43210 USABen Van Calster - Belgium & Luxembourg Gynaecol Oncol Grp BGOG, Leuven, BelgiumSang-Yoon Park - Natl Canc Ctr, Goyang, South KoreaJosep M. del Campo - Vall dHebron Univ Hosp, Dept Med Oncol, GEICO, Barcelona, SpainWerner Meier - AGO Germany & Evangel Hosp Dusseldorf, Arbeitsgemeinsch Gynaekol Onkol Study Grp AGO, Dept Gynecol & Obstet, Dusseldorf, GermanyAristotelis Bamias - Univ Athens, Alexandra Hosp, Dept Clin Therapeut, Athens, GreeceNicofetta Colombo - IRCCS, European Inst Oncol, Mario Negri Gynecol Oncol Grp MANGO, Milan, ItalyRobert M. Wenham - H Lee Moffitt Canc Ctr & Res Inst, Dept Gynecol Oncol, Gynecol Oncol Grp, Tampa, FL USAAl Covens - Univ Toronto, Toronto Sunnybrook Reg Canc Ctr, Div Gynecol Oncol, Toronto, ON, CanadaChristian Marth - Med Univ Innsbruck, Arbeitsgemeinsch Gynaekol Onkol Study Grp AGO Aus, Dept Obstet & Gynecol, Innsbruck, AustriaMansoor Raza Mirza - Rigshosp, NSGO, Dept Oncol, Copenhagen, DenmarkJudith R. Kroep - Leiden Univ, Med Ctr, Dept Med Oncol, Dutch Gynecol Oncol Grp DCOG, Leiden, NetherlandsHaijun Ma - Amgen Inc, Global Dev Oncol, Thousand Oaks, CA USACheryl A. Pickett - Amgen Inc, Global Dev Oncol, Thousand Oaks, CA USABradley J. Monk - Univ Arizona, Arizona Oncol US Oncol Network, Gynecol Oncol Grp, Phoenix, AZ USATRINOVA-3/ENGOT-ov2/GOG-3001 investigators
- Contributors
- David P Bender (Contributor) - University of Iowa, Obstetrics and Gynecology
- Resource Type
- Journal article
- Publication Details
- The lancet oncology, Vol.20(6), pp.862-876
- DOI
- 10.1016/S1470-2045(19)30178-0
- PMID
- 31076365
- NLM abbreviation
- Lancet Oncol
- ISSN
- 1470-2045
- eISSN
- 1474-5488
- Publisher
- Elsevier
- Number of pages
- 15
- Grant note
- Amgen
- Language
- English
- Date published
- 06/01/2019
- Academic Unit
- Obstetrics and Gynecology
- Record Identifier
- 9984315566002771
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