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.
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.
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|
|Not assessed, %||44||60||42|
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
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.