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Final results from GCIG/ENGOT/AGO‐OVAR 12, a randomised placebo‐controlled phase III trial of nintedanib combined with chemotherapy for newly diagnosed advanced ovarian cancer

Authors: Ray-Coquard, Isabelle; Cibula, David; Mirza, Mansoor R; Reuss, Alexander; Ricci, Caterina; Colombo, Nicoletta; Koch, Horst; +20 Authors

Final results from GCIG/ENGOT/AGO‐OVAR 12, a randomised placebo‐controlled phase III trial of nintedanib combined with chemotherapy for newly diagnosed advanced ovarian cancer

Abstract

AGO‐OVAR 12 investigated the effect of adding the oral triple angiokinase inhibitor nintedanib to standard front‐line chemotherapy for advanced ovarian cancer. At the primary analysis, nintedanib demonstrated significantly improved progression‐free survival (PFS; primary endpoint) compared with placebo. We report final results, including overall survival (OS). Patients with primary debulked International Federation of Gynaecology and Obstetrics (FIGO) stage IIB–IV newly diagnosed ovarian cancer were randomised 2:1 to receive carboplatin (area under the curve 5 or 6) plus paclitaxel (175 mg/m2) on day 1 every 3 weeks for six cycles combined with either nintedanib 200 mg or placebo twice daily on days 2–21 every 3 weeks for up to 120 weeks. Between December 2009 and July 2011, 1,366 patients were randomised (911 to nintedanib, 455 to placebo). Disease was considered as high risk (FIGO stage III with >1 cm residuum, or any stage IV) in 39%. At the final analysis, 605 patients (44%) had died. There was no difference in OS (hazard ratio 0.99, 95% confidence interval [CI] 0.83–1.17, p = 0.86; median 62.0 months with nintedanib vs. 62.8 months with placebo). Subgroup analyses according to stratification factors, clinical characteristics and risk status showed no OS difference between treatments. The previously reported PFS improvement seen with nintedanib did not translate into an OS benefit in the nonhigh‐risk subgroup. Updated PFS results were consistent with the primary analysis (hazard ratio 0.86, 95% CI 0.75–0.98; p = 0.029) favouring nintedanib. The safety profile was consistent with previous reports.

Keywords

Cancer Research, Indoles, Oncologie, Ovarian Neoplasms/therapy, Carboplatin, Placebos, tyrosine kinase inhibitor, Ovarian Neoplasms/pathology, Antineoplastic Combined Chemotherapy Protocols, Paclitaxel/adverse effects, nintedanib, Human health sciences, Medical Oncology - Radboud University Medical Center, Aged, 80 and over, Ovarian Neoplasms, Indoles/administration & dosage, Cytoreduction Surgical Procedures, Antineoplastic Combined Chemotherapy Protocols/administration & dosage, Middle Aged, Progression-Free Survival, ovarian cancer, Oncology, Chemotherapy, Adjuvant, Indoles/adverse effects, Female, Chemotherapy, Adjuvant/methods, Ovarian Neoplasms/mortality, Adult, Paclitaxel, overall survival, Radboudumc 17: Women's cancers RIHS: Radboud Institute for Health Sciences, Protein Kinase Inhibitors/adverse effects, Sciences de la santé humaine, Young Adult, Carboplatin/adverse effects, Chemotherapy, Adjuvant/adverse effects, Paclitaxel/administration & dosage, Ovary/surgery, Humans, Protein Kinase Inhibitors, Aged, Neoplasm Staging, Antineoplastic Combined Chemotherapy Protocols/adverse effects, Protein Kinase Inhibitors/administration & dosage, Ovary, Carboplatin/administration & dosage, antiangiogenic, anti-angiogenic; nintedanib; ovarian cancer; overall survival; tyrosine kinase inhibitor, antiangiogenic; nintedanib; ovarian cancer; overall survival; tyrosine kinase inhibitor;, Ovary/pathology, Follow-Up Studies

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    popularity
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    influence
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    This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
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selected citations
These citations are derived from selected sources.
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
47
Top 10%
Top 10%
Top 10%
Green