416O - Efficacy and safety of pasireotide LAR or everolimus alone, or in combination in patients with advanced carcinoids (NET) of the lung/thymus: Result...

Date 10 October 2016
Event ESMO 2016 Congress
Session Endocrine and neuroendocrine tumours
Topics Cytotoxic agents
Neuroendocrine Cancers
Therapy
Biological therapy
Presenter Piero Ferolla
Citation Annals of Oncology (2016) 27 (6): 136-148. 10.1093/annonc/mdw369
Authors P. Ferolla1, M.P. Brizzi2, T. Meyer3, W. Mansoor4, J. Mazieres5, C.D. Cao6, H. Lena7, A. Berruti8, V. Damiano9, W. Buikhuisen10, M. Stankovic11, N. Singh12, E. Chiodini13, G. Gislimberti14, K. Oberg15, E. Baudin16
  • 1Dept. Of Medical Oncology, Multidisciplinary NET Group, Umbria Regional Cancer Network and University of Perugia, 06126 - Perugia/IT
  • 2Department Of Oncology, University of Torino, Torino/IT
  • 3Oncology, Royal Free Hospital and UCL, London/GB
  • 4Department Of Medical Oncology, The Christie NHS Foundation Trust, Manchester/GB
  • 5Medical Oncology, CHU Toulouse, Hôpital de Larrey, Toulouse/FR
  • 6Medical Oncology, CHRU Lille, Lille/FR
  • 7Pneumologie, Centre Hospitalier Universitaire, Rennes/FR
  • 8Medical Oncology, University of Brescia, Brescia/IT
  • 9Department Dip.oncol. Endocr.molec.clinic, Azienda Ospedaliera Universitaria Policlinico Federico II-AOU Federico II, 80131 - Napoli/IT
  • 10Department Of Thoracic Oncology, The Netherlands Cancer Institute, Amsterdam/NL
  • 11Medical Affairs, Novartis Pharma Services Inc, Novi Beograd/RS
  • 12Pls Clinical Project Mgt, Cognizant Technology Solutions, Mumbai/IN
  • 13Clinical, Parexel, Origgio/IT
  • 14Oore-gmo, Gislimberti, Origgio/IT
  • 15Dep Of Medical Sciences, Uppsala University Hospital, Uppsala/SE
  • 16Endocrinology, Institut Gustave Roussy, Villejuif/FR

Abstract

Background

Advanced lung/thymus carcinoid is an area of high unmet medical need. In recent phase 3 RADIANT-4 study, everolimus (E) showed progression-free survival (PFS) benefit in patients (pts) with GI/lung NET. Pasireotide LAR (P, somatostatin analog [SSA]), has also shown potential antitumor activity in previous studies in NET. This phase 2 study evaluated efficacy and safety of E, P, and P + E in pts withprogressive carcinoids of lung/thymus.

Methods

Adult pts with metastatic RECIST progressive carcinoids of lung/thymus were randomized (1:1:1) to P (60 mg/month [mo] i.m.), E (10 mg/day orally) and P + E. Primary endpoint was progression free rate at mo 9 (PFR-9): proportion of pts at mo 9 with complete (CR), partial (PR) response or stable disease (SD) according to RECIST v.1.1. Key secondary end points were PFS, disease control rate and safety.

Results

124 pts were randomized to P (41), E (42), P + E (41). Median age = 64 yrs; atypical/typical carcinoid = 68.5%/31.5%; WHO performance status: 0/1/2 = 64%/34%/2%; primary tumor site: lung/thymus = 93.5%/6.5%; prior treatment (Tx): medication = 44%; radiotherapy = 27%; surgery/locoregional therapy = 97%; prior SSA = 48%. Tx discontinuation was seen in 65% pts (during core phase of 12 mos), mainly due to adverse events (AEs; 27%) and disease progression (PD; 27%). Primary endpoint, PFR-9: P = 39.0% (95% CI, 24.2, 55.5); E = 33.3% (19.6, 49.5); P + E = 58.5% (42.1, 73.7). Best overall response (9-mo) in all arms are listed in the table. AEs were primarily grade 1/2 in each arm; most common AEs regardless of study drug relationship in the P + E arm were hyperglycemia (88%), diarrhea (78%), weight decrease (56%), asthenia (37%), and stomatitis (34%).

P E P + E
CR, % 0 0 0
PR, % 2 2 2
SD, % 34 31 49
PD, % 17 2 0
Not assessed, % 44 60 42

Conclusions

LUNA study is the first randomized trial designed for lung and thymic carcinoids. The study met its primary endpoint showing promising PFR-9 in all Tx arms; particularly in the combination arm. No new safety signals were observed.

Clinical trial identification

EUDRACT number: 2011-002872-17

Legal entity responsible for the study

Novartis Pharma

Funding

Novartis Pharma

Disclosure

P. Ferolla: The study was sponsored by Novartis; Participation to Advisory boards and Steering Comitees for Novartis, Ipsen; Pfizer, Lexicon, Italfarmaco.

M. Stankovic, G. Gislimberti: "Other" from Novartis Pharma Inc, as Novartis Employee.

K. Oberg: Other from IPSEN, other from Novartis, outside the submitted work; .

E. Baudin: Personal fees from Novartis, during the conduct of the study.

All other authors have declared no conflicts of interest.