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: International Journal of Cancer

I. Ray-Coquard, D. Cibula, M.R. Mirza, A. Reuss, C. Ricci, N. Colombo, H. Koch, F. Goffin, A. González-Martin, P.B. Ottevanger, K. Baumann, L. Bjørge, A. Lesoin, A. Burges, P. Rosenberg, M. Gropp-Meier, M. Harrela, P. Harter, J.-S. Frenel, T. MinarikC. Pisano, A. Hasenburg, M. Merger, A. du Bois, on behalf of the AGO Study Group-led GCIG/ENGOT Intergroup Consortium

Research output: Contribution to journalArticlepeer-review

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. © 2019 UICC
Original languageEnglish
Pages (from-to)439-448
Number of pages10
JournalInt. J. Cancer
Volume146
Issue number2
DOIs
Publication statusPublished - 2020

Keywords

  • antiangiogenic
  • nintedanib
  • ovarian cancer
  • overall survival
  • tyrosine kinase inhibitor
  • alanine aminotransferase
  • aspartate aminotransferase
  • carboplatin
  • paclitaxel
  • placebo
  • antineoplastic agent
  • indole derivative
  • protein kinase inhibitor
  • abdominal pain
  • adult
  • advanced cancer
  • aged
  • alanine aminotransferase blood level
  • alopecia
  • anemia
  • arthralgia
  • Article
  • aspartate aminotransferase blood level
  • asthenia
  • backache
  • cancer staging
  • cancer survival
  • constipation
  • controlled study
  • decreased appetite
  • diarrhea
  • double blind procedure
  • drug safety
  • dysgeusia
  • dyspnea
  • fatigue
  • female
  • fever
  • headache
  • high risk patient
  • hot flush
  • human
  • hypertension
  • hypokalemia
  • hypomagnesemia
  • insomnia
  • intention to treat analysis
  • leukopenia
  • major clinical study
  • multiple cycle treatment
  • myalgia
  • nausea
  • neutropenia
  • ovary cancer
  • pain
  • paresthesia
  • peripheral edema
  • peripheral neuropathy
  • phase 3 clinical trial
  • priority journal
  • progression free survival
  • randomized controlled trial
  • rash
  • response evaluation criteria in solid tumors
  • risk assessment
  • risk factor
  • sensory neuropathy
  • thrombocytopenia
  • treatment duration
  • treatment withdrawal
  • upper abdominal pain
  • urinary tract infection
  • very elderly
  • vomiting
  • adjuvant chemotherapy
  • adverse event
  • clinical trial
  • cytoreductive surgery
  • follow up
  • middle aged
  • mortality
  • multicenter study
  • ovary
  • ovary tumor
  • pathology
  • procedures
  • surgery
  • young adult
  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Combined Chemotherapy Protocols
  • Carboplatin
  • Chemotherapy, Adjuvant
  • Cytoreduction Surgical Procedures
  • Female
  • Follow-Up Studies
  • Humans
  • Indoles
  • Middle Aged
  • Neoplasm Staging
  • Ovarian Neoplasms
  • Ovary
  • Paclitaxel
  • Placebos
  • Progression-Free Survival
  • Protein Kinase Inhibitors
  • Young Adult

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