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1196 A randomised phase II study of combination chemotherapy with nintedanib/placebo in advanced/recurrent endometrial cancer. FANDANGO/ENGOT-EN1/FANDANGO
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  1. M Mirza1,
  2. D Berton2,
  3. I Vergote3,
  4. R Depont Christensen4,
  5. A Floquet5,
  6. J Maenpaa6,
  7. I Braicu7,
  8. S Altintas8,
  9. P Follana9,
  10. A Ør Knudsen10,
  11. B Ataseven11,
  12. F Selle12,
  13. C Lundgren13,
  14. J Huober14,
  15. M Fabbro15,
  16. H Denys16,
  17. P Heudel17,
  18. M Magnusson4,
  19. K Lindemann18 and
  20. J Sehouli7
  1. 1Rigshospitaletd, Denmark
  2. 2GINECO: Groupe d’Investigateurs National des Etudes des Cancers Ovariens et du sein and ICO Centre René Gauducheau, Saint-Herblain, France
  3. 3BGOG: Belgium and Luxembourg Gynaecological Oncology Group and Universitaire Ziekenhuizen Leuven, , Belgium
  4. 4NSGO-CTU
  5. 55GINECO: Groupe d’Investigateurs National des Etudes des Cancers Ovariens et du sein and Institut Bergonié, Bordeaux, France
  6. 6Tampere University Hospital, Finland
  7. 7Charité, Germany
  8. 8BGOG: Belgium and Luxembourg Gynaecological Oncology Group and Antwerp University Hospital, Belgium
  9. 9GINECO: Groupe d’Investigateurs National des Etudes des Cancers Ovariens et du sein and Centre Antoine Lacassagne Nice, France
  10. 10NSGO-CTU: Nordic Society of Gynaecological Oncology – Clinical Trial Unit and University Hospital Odense, Denmark
  11. 11NOGGO: Northeast German Society of Gynaecological Oncology and Kliniken Essen Mitte, , Germany
  12. 12GINECO: Groupe d’Investigateurs National des Etudes des Cancers Ovariens et du sein and Groupe Hospitalier Diaconesses, Paris, France
  13. 13NSGO-CTU: Nordic Society of Gynaecological Oncology – Clinical Trial Unit and Karolinska University Hospital, Stockholm, Sweden
  14. 14NOGGO: Northeast German Society of Gynaecological Oncology and University Hospital Ulm, Germany
  15. 15GINECO: Groupe d’Investigateurs National des Etudes des Cancers Ovariens et du sein and ICM Val d’Aurelle, Montpellier, France
  16. 16BGOG: Belgium and Luxembourg Gynaecological Oncology Group and Gent University Hospital, Belgium
  17. 17GINECO: Groupe d’Investigateurs National des Etudes des Cancers Ovariens et du sein and Centre Léon Bérard, Lyon
  18. 18Oslo university hospital, Norway

Abstract

Introduction/Background*Endometrial cancer (EC) patients (Pts) with advanced and recurrent disease relapse despite treatment with combination chemotherapy and have a short progression-free survival (PFS). Nintedanib (N) is a potent, orally available triple receptor tyrosine kinase inhibitor targeting VEGFR 1–3, PDGFR α/β, and FGFR 1–3. This study explored the preliminary efficacy of nintedanib in EC.

Methodology The primary objective of this placebo-controlled, randomized study was to evaluate efficacy defined by median PFS of concomitant and maintenance N against placebo (P) in combination with chemotherapy. Patients with histologically confirmed stage IIIC2 or IVA & B or relapsed after adjuvant therapy for stage I-III disease; prior surgery; adjuvant chemotherapy; radiation therapy; hormonal therapy in metastatic setting; with measurable/non-measurable disease were permitted. Pts were randomized 1:1 to receive N 200mg or P, twice daily days 2–21 during chemotherapy (six cycles of Carboplatin (AUC5) and paclitaxel (175mg/m2) every 21 days) and continuously in maintenance phase. N/P was continued until disease progression, unacceptable toxicity, or withdrawal of consent. Stratification by stage of disease, prior adjuvant chemotherapy and measurable/non-measurable disease. This is an ENGOT Model A study. Clinical trial information: NCT02730416.

Result(s)*146 of 148 pts were eligible for PFS: 72N/74P; mean age 66yrs; FIGO stage III 18%, IV 42%, recurrent 40%; follow-up 30 mo. N added to chemotherapy did not improve PFS (119 events) as compared to chemotherapy plus P: median for N 8.3 vs. for P 7.2 mo; hazard ratio (HR) adjusted for stratification factors 1.03; 95% confidence interval (CI),[0.71 to 1.48]; p0.879. Median overall survival (85 events) for N 20 vs. for P 22 mo; HR: 1.10; CI: 0.72–1.69; p0.665. Treatment-emerged grade 3–4 adverse events were higher in N vs P arm: liver function tests 13%/0%; diarrhea 12%/6%; neutropenia 21%/14%; asthenia 4%/1%. Patient-reported outcomes will be reported.

Conclusion*Addition of nintedanib to chemotherapy did not improve PFS nor OS. This regimen cannot be recommended to undergo further testing in a phase III trial.

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