1132O - Everolimus (EVE) for the treatment of advanced pancreatic neuroendocrine tumors (pNET): Final overall survival (OS) results of a randomized, double...

Date 27 September 2014
Event ESMO 2014
Session Neuroendocrine tumours
Topics Anti-Cancer Agents & Biologic Therapy
Neuroendocrine Cancers
Presenter James Yao
Citation Annals of Oncology (2014) 25 (suppl_4): iv394-iv405. 10.1093/annonc/mdu345
Authors J.C. Yao1, M. Pavel2, C. Lombard-Bohas3, E. Van Cutsem4, D. Lam5, T. Kunz6, U. Brandt7, J. Capdevila8, E.G.E. De Vries9, P. Tomassetti10, T. Hobday11, R. Pommier12
  • 1Gastrointestinal Medical Oncology, MD Anderson Cancer Center, 77030-4095 - Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston/US
  • 2Dept Of Gastroenterology & Hepatology, Charité Universitätsmedizin Berlin, 13353 - Berlin/DE
  • 3Medical Oncology, Hôpital Edouard Herriot Hospices Civils De Lyon, 69737 - Lyon Cedex /FR
  • 4Digestive Oncology Unit, University Hospitals Gasthuisberg/Leuven and KU Leuven, Leuven/BE
  • 5Oncology, Novartis, East Hanover/US
  • 6Oncology, Novartis Pharmaceuticals Corporation, East Hanover/US
  • 7Oncology, Novartis International AG, Basel/CH
  • 8Medical Oncology, Vall d'Hebron University Hospital, 08035 - Barcelona/ES
  • 9Department Of Medical Oncology, UMCG, Groningen/NL
  • 10Department Of Medical And Surgical Sciences, University of Bologna, Bologna/IT
  • 11Department Of Oncology, Mayo Clinic College of Medicine, 55905 - Rochester/US
  • 12Division Of Surgical Oncology, Oregon Health & Science University, 97239 - Portland/US

 

Abstract

Aim

EVE significantly improved median progression-free survival vs PBO in patients (pts) with pNET by 6.4 months in RADIANT-3 (11.0 vs 4.6 months; HR 0.35, 95% CI 0.27-0.45; p < 0.001). Here we present final OS results and safety findings.

Methods

Pts with progressive advanced, low- or intermediate-grade pNET were randomized to EVE 10mg/d (n = 207) or PBO (n = 203); both with best supportive care. Upon disease progression during double-blind phase, crossover from PBO to open-label EVE was allowed. At the time of unblinding (cutoff, Jun 3, 2010), all ongoing pts transitioned into the extension phase to receive open-label EVE. After 256 events, OS analysis was performed using a stratified log-rank test in the intent-to-treat patient population (N = 410; all randomized pts).

Results

Of 410 pts, 225 switched to open-label EVE; including 85% of pts initially randomized to PBO (172 of 203). Median open-label EVE exposure was 67.1 weeks (range 1-189) in pts initially randomized to EVE and 44.0 weeks (range 0-261) in pts randomized to PBO. Median OS (95% CI) was 44.0 (35.6-51.8) months for EVE arm and 37.7 (29.1-45.8) months for PBO arm (HR 0.94, 95% CI 0.73-1.20; p = 0.30; boundary 0.0249). Adverse events reported during the open-label phase (n = 221) were consistent with those observed during blinded treatment; the most common included stomatitis (47%), diarrhea (44%), and rash (40%).

Estimated OS rates

Kaplan-Meier estimates [95% CI] at: EVE 10 mg/d (n = 207) PBO (n = 203)
12 mo 82.6 [76.6-87.2] 82.0 [75.9-86.7]
24 mo 67.7 [60.7-73.8] 64.0 [56.8-70.2]
36 mo 56.7 [49.4-63.3] 50.9 [43.6-57.7]
48 mo 46.9 [39.7-53.8] 41.3 [34.3-48.1]
60 mo 34.7 [27.7-41.7] 35.5 [28.7-42.4]

Conclusions

EVE demonstrated a median OS of 44 months, the longest OS reported for progressive advanced pNET pts in a phase 3 study. A clinically important improvement of 6.3 months in median OS vs PBO was observed, although the difference did not reach statistical significance. Crossover of majority of pts (85%) may also have confounded OS. The safety of EVE was consistent with previous experience.

Disclosure

J.C. Yao: Corporate-sponsored research (Novartis); Consultancy (Novartis); M. Pavel: Honoraria for advisory board meeting and presentations (Novartis, IPSEN, Pfizer); Research grant (Novartis); C. Lombard-Bohas: Membership on an advisory board or board of directors (Novartis); E. van Cutsem: Research grant paid to university by Novartis; D. Lam: Employee (Novartis); Stock ownership (Novartis); T. Kunz: Employee (Novartis); Stock ownership (Novartis); U. Brandt: Employee (Novartis); Stock ownership (Novartis); E.G.E. De Vries: Support for the execution of the trial made available to the UMCG; T. Hobday: Research funding (Novartis); R. Pommier: Consultant (Novartis, Pfizer). All other authors have declared no conflicts of interest.