Bevacizumab Combined With Weekly Paclitaxel, Pegylated Liposomal Doxorubicin, or Topotecan in Platinum-Resistant Recurrent Ovarian Cancer: Analysis by Chemotherapy Cohort of the Randomized Phase III AURELIA Trial

Poveda, Andrés; Selle, Frédèric; Hilpert, Felix; Reuß, Alexander; Savarese, Antonella; Vergote, Ignace; Witteveen, Petronella O.; Bamias, Aristotelis; Scotto, Nana; Mitchell, Lada; Pujade-Lauraine, Éric

doi:10.1200/jco.2015.63.1408

Cited by 173 publications

(113 citation statements)

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“…However, it has proven exceptionally difficult to show a statistically significant prolongation of OS with the addition of targeted therapy to standard treatments in patients with ovarian cancer [10][11][12][13][14][15][16][17][18][26][27][28]. Potential confounding factors for OS include the long postprogression survival period, the administration of multiple postprogression therapies, and the potential for postprogression crossover [27,29].…”

Section: Discussionmentioning

confidence: 99%

“…Evidence suggests that the Ang2 pathway plays a role in the pathophysiology of ovarian cancer [6][7][8] and upregulation of Ang2 is correlated with poor prognosis in women with recurrent ovarian cancer [9]. Several antiangiogenic agents that target the VEGF pathway have been shown to improve progression-free survival (PFS) in patients with ovarian cancer; however, a statistically significant improvement in OS has not been demonstrated [10][11][12][13][14][15][16][17][18].…”

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: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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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“…Any additional conjecture to explain the ORR differences between those cohorts would be speculative given that this phase 1b study was not designed to compare efficacy. There is some indication of a clinical benefit in an ongoing randomized phase 3 study of patients with platinum-resistant recurrent ovarian cancer receiving bevacizumab 10 mg/kg every 2 weeks or 15 mg/kg every 3 weeks plus PLD, topotecan, or paclitaxel [40]. Exploratory analyses from that study suggested median PFS duration of 5.4 months and 5.8 months in the PLD and topotecan cohorts, respectively; ORRs were 18.3% and 22.8%, respectively.…”

Section: Discussionmentioning

confidence: 99%

A phase 1b study of trebananib in combination with pegylated liposomal doxorubicin or topotecan in women with recurrent platinum-resistant or partially platinum-sensitive ovarian cancer

Vergote

Schilder

Pippitt

et al. 2014

Gynecologic Oncology

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Objective. To examine the tolerability and antitumor activity of trebananib plus pegylated liposomal doxorubicin (PLD) or topotecan in recurrent platinum-resistant or partially platinum-sensitive ovarian cancer.Methods. In this open-label phase 1b study, patients received trebananib 10 mg/kg or 15 mg/kg IV QW plus PLD 50 mg/m 2 (cohorts A1 and A3, respectively) or topotecan 4 mg/m 2 (cohorts B1 and B3, respectively). Endpoints were dose-limiting toxicity (DLT; primary); treatment-emergent adverse events (AEs), overall response rate, anti-trebananib antibodies, and pharmacokinetics (secondary).Results. 103 patients were enrolled. One patient in A1 and B1 had DLTs. Across all cohorts, the most common AEs were nausea, fatigue, and peripheral edema. Across both trebananib plus PLD cohorts (A1/A3), grade 4 AEs were pulmonary embolism, disease progression, and anemia. Two patients had grade 5 intestinal perforation (n = 1) and sudden death (n = 1). Across both trebananib plus topotecan cohorts (B1/B3), grade 4 AEs were neutropenia, hypokalemia, decreased granulocyte count, chest pain, dyspnea, decreased neutrophil count, and pulmonary embolism. Two patients had grade 5 disease progression. One patient had grade 5 pleural effusion associated with progressive disease. Confirmed objective response rates were 36.0% (A1), 34.8% (A3), 16.7% (B1), and 0.0% (B3). Median progression-free survival duration (months) was 7.4 (A1), 7.1 (A3), 3.5 (B1), and 3.1 (B3), respectively. No drug-drug interactions were apparent.

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“…Therefore, various immunotherapeutic approaches for ovarian cancer including antibodies, immune checkpoint inhibitors, vaccines, and adoptive cell therapy have recently entered clinical testing (6). Bevacizumab and cetuximab are among monoclonal antibodies which showed promising results in clinical trials (18,19). Immune checkpoints are specific molecules with the ability to inhibit powerful immunologic effector cells.…”

Section: Immunotherapy In Ovarian Cancermentioning

confidence: 99%

Cancer-Testis Antigens: A Novel Group of Tumor Biomarkers in Ovarian Cancers

et al. 2016

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Context: Ovarian cancer is the most fatal gynecological malignancy with no effective screening strategy for early detection. As most cases are being detected in advance stages, conventional therapies are not beneficial for the majority of patients. Cancer-testis antigens (CTAs) are a group of tumor associated antigens with specific expression pattern in cancers which potentiate them for application as cancer biomarkers and targets for immunotherapy. Evidence Acquisition: We performed a computerized search of the MEDLINE/PUBMED databases with key words: ovarian cancer, cancer-testis antigen, biomarker and immunotherapy.

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Bevacizumab Combined With Weekly Paclitaxel, Pegylated Liposomal Doxorubicin, or Topotecan in Platinum-Resistant Recurrent Ovarian Cancer: Analysis by Chemotherapy Cohort of the Randomized Phase III AURELIA Trial

Cited by 173 publications

References 10 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

A phase 1b study of trebananib in combination with pegylated liposomal doxorubicin or topotecan in women with recurrent platinum-resistant or partially platinum-sensitive ovarian cancer

Cancer-Testis Antigens: A Novel Group of Tumor Biomarkers in Ovarian Cancers

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