LBA27 - Phase 2 study of second-line dovitinib (TKI258) in patients with fibroblast growth factor receptor 2 (FGFR2)-mutated or -nonmutated advanced and/or...

Date 28 September 2014
Event ESMO 2014
Session Gynaecological cancers
Topics Anticancer Agents
Endometrial Cancer
Translational Research
Basic Principles in the Management and Treatment (of cancer)
Biological Therapy
Presenter Gottfried Konecny
Citation Annals of Oncology (2014) 25 (5): 1-41. 10.1093/annonc/mdu438
Authors G.E. Konecny1, N. Finkler2, A.A. Garcia3, D. Lorusso4, P. Lee5, R. Rocconi6, P.C..C. Fong7, M. Squires8, K. Mishra9, A. Upalawanna9, Y. Wang9, R. Kristeleit10
  • 1Gynecologic Oncology, Hematology & Oncology, UCLA Westwood Oncology Hematology, 90095 - Los Angeles/US
  • 2Gynecologic Oncology, Florida Hospital Cancer Institute, Orlando/US
  • 3Division Of Medical Oncology, University of Southern California, Keck School of Medicine, 90033 - Los Angeles/US
  • 4Gynecologic Oncology, Department Of Surgery, National Cancer Institute of Milan, 20133 - Milan/IT
  • 5Division Of Gynecology/oncology, Duke University Medical School, Durham/US
  • 6Gynecologic Oncology, University of South Alabama, Mitchell Cancer Institute, Mobile/US
  • 7Medical Oncology, Auckland Hospital and University of Auckland, Auckland, Auckland/NZ
  • 8Oncology Correlative Sciences, Novartis Pharma AG, Basel/CH
  • 9Oncology Global Development, Novartis Pharmaceuticals Corporation, East Hanover/US
  • 10Uclh Dept. Of Oncology, UCL - University College London Cancer Institute, London/GB



Activating mutations in FGFR2, identified in 10%-15% of primary endometrial cancers (ECs), are associated with disease progression and poor outcome. Here, we evaluate dovitinib, a potent tyrosine kinase inhibitor of FGFR, VEGFR, and PDGFR, as second-line therapy in patients (pts) with FGFR2-mutated (FGFR2mut) or -nonmutated (FGFR2nonmut) EC.


Women with progressive disease after first-line chemotherapy for advanced and/or metastatic EC were treated with oral dovitinib 500 mg/day on a 5-days-on/2-days-off schedule. Primary endpoint was percentage of pts progression-free (by investigator assessment) after 18 weeks. The trial used a 2-stage design for each group (FGFR2mut and FGFR2nonmut); stage 2 could proceed if ≥ 8 of the first 20 treated pts (40%) met the primary endpoint. Secondary endpoints included response rate, PFS, overall survival (OS), and safety.


Of 248 prescreened pts, 11% were FGFR2mut. The study enrolled 53 pts (22 FGFR2mut, 31 FGFR2nonmut); all pts discontinued, mostly due to progressive disease (66%) or adverse events (AE; 26%). The observed 18-week PFS rates were 32% (FGFR2mut) and 29% (FGFR2nonmut). The study did not proceed to stage 2 based on the predefined criteria. However, the 18-week PFS rates from a Kaplan Meier analysis were 48% (FGFR2mut) and 38% (FGFR2nonmut). The disease control rate (≥ stable disease [SD]) was 64% (59% SD, 5% partial response [PR]) and 52% (35% SD, 16% PR) in the FGFR2mut and FGFR2nonmut groups, respectively. Median PFS (4.1 vs 2.7 months) and OS (20.2 vs 9.3 months) trended higher in the FGFR2mut group. AEs suspected to be study drug related were similar between groups. Most common grade 3/4 AEs were hypertension (17%) and diarrhea (9%). Of the 5 on-treatment deaths, 4 were due to EC and 1 was due to cardiac arrest.


Single-agent dovitinib demonstrated clinically meaningful activity in both groups and a trend toward greater median PFS and OS in the FGFR2mut group. The safety profile was similar to that observed in other dovitinib trials.


A.A. Garcia: Consultancy and research funding from Novartis Pharmaceuticals; D. Lorusso: Consultancy, research funding & membership on Board of Directors or advisory committee for Roche. Research funding &membership on Board of Directors or advisory committee for PharmaMar. Membership on Board of Directors or advisory committee for Amgen; P.C. Fong: Honoraria received from Novartis; M. Squires: Employment at Novartis Pharma AG; K. Mishra, A. Upalawanna and Y. Wang: Employment at Novartis Pharmaceuticals Corporation; R. Kristeleit: Membership on an entity's Board of Directors or advisory committees for Novartis. All other authors have declared no conflicts of interest.