Anti-angiopoietin therapy with trebananib for recurrent ovarian cancer (TRINOVA-1): a randomised, multicentre, double-blind, placebo-controlled phase 3 trial

Monk, Bradley J.; Poveda, Andrés; Vergote, Ignace; Raspagliesi, Francesco; Fujiwara, Keiichi; Bae, Duk Soo; Oaknin, Ana; Ray‐Coquard, Isabelle; Provencher, Diane; Karlan, Beth Y.; Lhommé, C.; Richardson, Gary; Rincón, Dolores Gallardo; Coleman, Robert L.; Herzog, Thomas J.; Marth, Christian; Brize, Arija; Fabbro, Michel; Redondo, Andrés; Bamias, Aristotelis; Tassoudji, Marjan; Navale, Lynn; Warner, Douglas; Oza, Amit M.

doi:10.1016/s1470-2045(14)70244-x

Cited by 275 publications

(173 citation statements)

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“…Eligibility criteria for TRINOVA-1 have been reported previously [20]. Briefly, women (≥18 years) were eligible if they had measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 [22]; as a result, patients with only ascites or pleural effusion at baseline were excluded from the study.…”

Section: Patientsmentioning

confidence: 99%

“…As previously described [20], the planned population size of 900 patients (followed up until at least 510 patients had disease progression or died) was estimated to provide 90% statistical power to detect a 33% reduction in the hazard of progression or death while limiting the type I error to 5%. A prespecified interim analysis of OS was performed at the time of primary analysis of PFS [20].…”

Section: Statistical Analysesmentioning

confidence: 99%

“…A prespecified interim analysis of OS was performed at the time of primary analysis of PFS [20]. Primary analysis of OS was conditional on a demonstration of statistically significant improvement in PFS and was planned for when a minimum of 600 deaths had occurred.…”

Section: Statistical Analysesmentioning

confidence: 99%

“…In a randomized, placebo-controlled, double-blind, phase 3 study (TRINOVA-1), women with recurrent ovarian cancer receiving paclitaxel plus trebananib 15 mg/kg once weekly (QW) had significantly prolonged PFS (primary endpoint) compared with patients who received paclitaxel plus placebo (7.2 versus 5.4 months; hazard ratio [HR], 0.66; 95% CI, 0.57-0.77; P b 0.0001) [20] without impairment of quality of life [21]. We report the mature analysis of OS in this study.…”

Section: Introductionmentioning

confidence: 99%

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Final results of a phase 3 study of trebananib plus weekly paclitaxel in recurrent ovarian cancer (TRINOVA-1): Long-term survival, impact of ascites, and progression-free survival-2

Monk

Poveda

Vergote

et al. 2016

Gynecologic Oncology

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• Trebananib did not improve overall survival in the intent-to-treat population.• Trebananib improved overall survival in patients with baseline ascites.• Trebananib prolonged time to second disease progression. Purpose. Trebananib, a peptibody that blocks binding of angiopoietin-1 and -2 to Tie2, significantly prolonged progression-free survival (PFS) in patients with recurrent epithelial ovarian cancer in the phase 3 TRINOVA-1 study. We report overall survival (OS) in the intent-to-treat population and clinically relevant subgroups and time to second disease progression (PFS-2). Patients and methods. Women with recurrent disease (platinum-free interval b 12 months) were randomized to receive intravenous paclitaxel 80 mg/m 2 (3 weeks on/1 week off) plus intravenous trebananib 15 mg/kg or placebo, weekly. OS in the intent-to-treat population was a key secondary endpoint. Exploratory analysis of PFS-2 was conducted according to guidance by the European Medicines Agency. Results. Median OS was not significantly improved with trebananib compared with placebo (19.3 versus 18.3 months; HR, 0.95; 95% CI, 0.81-1.11; P = 0.52) in the intent-to-treat population (n = 919). In subgroup analysis, trebananib improved median OS compared with placebo (14.5 versus 12.3 months; HR, 0.72; 95% CI, 0.55-0.93; P = 0.011) in patients with ascites at baseline (n = 295). In the intent-to-treat population, trebananib significantly improved median PFS-2 compared with placebo (12.5 versus 10.9 months; HR, 0.85; 95% CI, 0.74-0.98; P = 0.024). The incidence and type of adverse events in this updated analysis was consistent with that described in the primary analysis; no new safety signals were detected. a b s t r a c t a r t i c l e i n f oConclusions. OS was not significantly longer in the intent-to-treat population, although there was an improvement in OS in patients with ascites receiving trebananib. PFS-2 confirmed that the PFS benefit associated with trebananib was maintained through the second disease progression independent of the choice of subsequent therapy.

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Section: Patientsmentioning

confidence: 99%

Section: Statistical Analysesmentioning

confidence: 99%

Section: Statistical Analysesmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Final results of a phase 3 study of trebananib plus weekly paclitaxel in recurrent ovarian cancer (TRINOVA-1): Long-term survival, impact of ascites, and progression-free survival-2

Monk

Poveda

Vergote

et al. 2016

Gynecologic Oncology

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“…In the phase III TRINOVA-1 trial trebananib in combination with weekly paclitaxel prolonged significantly PFS in patients with recurrent ovarian cancer [70]. In metastatic renal cell cancer initial data indicate a superior efficacy when trebananib was added to sunitinib but also associated with a higher toxicity rate [71].…”

Section: Trebananibmentioning

confidence: 99%

Novel anti-angiogenic therapeutic strategies in colorectal cancer

Tampellini

Sonetto

Scagliotti

2016

Expert Opinion on Investigational Drugs

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Alisertib in Combination With Weekly Paclitaxel in Patients With Advanced Breast Cancer or Recurrent Ovarian Cancer

et al. 2019

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IMPORTANCE There is an unmet medical need for the treatment of recurrent ovarian cancer, and new approaches are needed to improve progression-free survival (PFS) and overall survival. OBJECTIVE This phase 1/2 study evaluated the activity of alisertib in combination with weekly paclitaxel in patients with breast (phase 1) and ovarian cancer (phase 1 and phase 2). DESIGN, SETTING, AND PARTICIPANTS An open-label phase 1 and randomized phase 2 clinical trial conducted from April 16, 2010, for phase 1 and March 28, 2012, to August 12, 2013, for phase 2 was conducted at 33 sites (United States, France, and Poland). Data are reported from a cutoff date of August 12, 2014, with a median duration of follow-up of 7.2 months in the alisertib plus paclitaxel arm and 4.6 months in the paclitaxel arm. A total of 191 women with advanced breast (phase 1 only) or recurrent ovarian cancer were enrolled, including 142 patients randomized to alisertib plus paclitaxel (n = 73) or paclitaxel alone (n = 69) in the phase 2 study. INTERVENTIONS Patients were randomized 1:1 stratified by platinum-free interval (refractory, 0-6 months, 6-12 months) and prior weekly taxane treatment (yes, no) to receive alisertib 40 mg twice per day orally and 3 days on and 4 days off for 3 weeks, plus paclitaxel (60 mg/m 2 intravenously, days 1, 8, and 15), or weekly paclitaxel 80 mg/m 2 intravenously in 28-day cycles. MAIN OUTCOMES AND MEASURES Primary endpoint was PFS; primary efficacy analysis and safety analysis used modified intention to treat (mITT) population (all randomized patients who received Ն1 dose of study drug). RESULTS The median age for the 191 patients enrolled in phase 1 was 59 (range, 29-75) years. The median age for the 142 patients enrolled in phase 2 was 63 (range, 30-81) years for patients receiving alisertib plus paclitaxel and 61 (range, 41-81) years for patients receiving paclitaxel. At data cutoff, 107 (75%) patients had a documented PFS event; 52 (71%) in the alisertib plus paclitaxel arm, and 55 (80%) in the paclitaxel arm. Median PFS was 6.7 months with alisertib plus paclitaxel vs 4.7 months with paclitaxel (HR, 0.75; 80% CI, 0.58-0.96; P = .14; 2-sided P value cutoff = .20 to be considered worthy of further investigation). Drug-related grade 3 or higher adverse events were reported in 63 (86%) vs 14 (20%) patients in the alisertib plus paclitaxel and paclitaxel arms, including 56 (77%) vs 7 (10%) neutropenia, 18 (25%) vs 0 stomatitis, and 10 (14%) vs 2 (3%) anemia; 54 (74%) vs 17 (25%) had adverse events leading to dose reductions. Two patients died during the study (1 in each arm); neither death was considered related to study drug. CONCLUSIONS AND RELEVANCE The primary endpoint, PFS, significantly favored alisertib plus paclitaxel over paclitaxel alone. Further investigation is warranted.

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Anti-angiopoietin therapy with trebananib for recurrent ovarian cancer (TRINOVA-1): a randomised, multicentre, double-blind, placebo-controlled phase 3 trial

Cited by 275 publications

References 26 publications

Final results of a phase 3 study of trebananib plus weekly paclitaxel in recurrent ovarian cancer (TRINOVA-1): Long-term survival, impact of ascites, and progression-free survival-2

Final results of a phase 3 study of trebananib plus weekly paclitaxel in recurrent ovarian cancer (TRINOVA-1): Long-term survival, impact of ascites, and progression-free survival-2

Novel anti-angiogenic therapeutic strategies in colorectal cancer

Alisertib in Combination With Weekly Paclitaxel in Patients With Advanced Breast Cancer or Recurrent Ovarian Cancer

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