LBA45 - A randomized multicentre phase II study of pazopanib plus best supportive care (BSC) vs BSC alone in metastatic gastroIntestinal stromal tumors (GI...

Date 29 September 2014
Event ESMO 2014
Session Sarcoma
Topics Anti-Cancer Agents & Biologic Therapy
Supportive Care
GIST
Presenter Jean-Yves Blay
Citation Annals of Oncology (2014) 25 (5): 1-41. 10.1093/annonc/mdu438
Authors J. Blay1, J. Domont2, C. Cropet1, A. Italiano3, E. Bompas4, P. Cassier1, I.L. Ray-Coquard1, M. Rios5, A. Adenis6, O. Mir7, O. Bouché8, B. Bui3, F. Duffaud9, F. Bertucci10, N. Isambert11, A. Belleville1, E. Remir1, J. Gautier12, A. Le Cesne7, D. Perol13
  • 1University Claude Bernard Lyon I, Centre Léon Bérard, 69008 - Lyon/FR
  • 2Dept. Of Medicine, Institut de Cancérologie Gustave Roussy, 94805 - Villejuif CEDEX/FR
  • 3Medical Oncology, Institute Bergoni, FR-33076 - Bordeaux CEDEX/FR
  • 4Oncology, ICO Institut de Cancerologie de l'Ouest René Gauducheau, 44000 - Nantes/FR
  • 5Medecine, Centre Alexis Vautrin, 54000 - Nancy/FR
  • 6Medical Oncology, Centre Oscar Lambret, 59020 - Lille/FR
  • 7Medecine, Institut Gustave Roussy, FR-94805 - Villejuif CEDEX/FR
  • 8Gastroenterology, Centre Hospitalier Universitaire Robert Debré, Reims/FR
  • 9Medical Oncology, C.H.U. La Timone Adultes, 13385 - Marseille CEDEX /FR
  • 10Medical Oncology, Institut Paoli Calmette, Marseille/FR
  • 11Unité De Phase I, Centre Georges François Leclerc, 77980 - Dijon/FR
  • 12Biostatistics Unit, Centre Leon Berard, FR-69008 - Lyon CEDEX/FR
  • 13Biostatistics Unit, Centre L, FR-69008 - Lyon CEDEX/FR

Abstract

Aim

GIST is the most common mesenchymal neoplasm of the gastrointestinal tract. In unresectable and metastatic or locally advanced disease, imatinib followed by sunitinib, then regorafenib represent the standard treatments in 1st, 2nd and 3rd line, respectively. Pazopanib is an active treatment in soft tissue sarcomas; it has never been evaluated in a randomized setting in advanced GIST.

Methods

Eligible adult patients (pts) with adequate organ functions were randomly assigned (1:1) to receive P + BSC or BSC alone. Randomization was stratified by number of prior drugs (2 vs > = 3). The primary endpoint was Progression-Free Survival (PFS). 80 pts were planned to detect an improvement in the 4-month PFS rate (PFS-4m) from 15% (BSC alone) to 45% (P + BSC) with 5% two-sided α error and 80% power. Secondary objectives included Best Overall Response (BOR), overall survival and safety

Results

From Apr 11 to Dec 13, 81 pts were randomized: 40 to P + BSC and 41 to BSC alone. Median age was 63 y (27-85), 70% were males. The intent-to-treat analysis based on investigator-assessed progression showed a significant improvement in PFS with PFS-4m of 47.7% (95% CI 30.9 to 62.7) for P + BSC vs 19.5% (95% CI 9.2 to 32.7) for BSC (HR: 0.56, 95% CI 0.34 to 0.93; stratified log-rank: p = 0.02). 36/41 pts allocated to BSC arm received P following investigator-assessed progression. BOR assessed by central review showed stable disease in 84.2% vs 70.7% and progressive disease in 15.8% vs 26.8% of pts in P + BSC and BSC arms, respectively. 52.5% of pts receiving P + BSC experienced at least one Serious Adverse Event (SAE) vs 14.6% of pts receiving BSC alone. In P + BSC arm, the more frequent SAE were gastrointestinal disorders (n = 7; 17.5%), deterioration of global health status (n = 6; 15%) and pulmonary embolism (n = 5; 12.5%).

Conclusions

P combined to BSC improves PFS in pts with advanced GIST resistant to imatinib and sunitinib.

Disclosure

J-Y. Blay: Research funding and honoraria from GSK, Novartis, Roche, Pfizer, Bayer; A. Italiano: Research support and honoraria from GSK; P. Cassier: Honoraria from GSK and Servier Travel reimbursment from Novartis, Roche and Servier Research support from Novartis; I.L. Ray-Coquard: Honoraria and research support from GSK & Roche; O. Mir: has acted as a consultant/speaker for Astra-Zeneca, Bayer, GSK, Novartis, Pfizer, Roche and Servier; A. Belleville, J. Gautier and D. Perol: Research support from GSK; A. Le Cesne: Honoraria & Research support from GSK, Pharmamar, Novartis. All other authors have declared no conflicts of interest.