High-Dose and High-Frequency Lanreotide Autogel in Acromegaly Patients Inadequately Controlled on Conventional Somatostatin Analog Therapy: A Randomized, Open Label, Multicenter Study
Presentation Number: SUN 429
Date of Presentation: April 2nd, 2017
Andrea Giustina*1, Gherardo Mazziotti2, Salvatore Cannavo3, Roberto Castello4, Giorgio Arnaldi5, Giovanna Bugari6, Renato Cozzi7, Diego Ferone8, Anna Maria Formenti1, Pietro Maffei9, Filippo Maffezzoni1, Marcella Montini10, Massimo Terzolo11 and Ezio Ghigo12
1University of Brescia, Italy, 2ASST Carlo Poma, Mantua, ITALY, 3University of Messina, Messina, Italy, 4University of Verona, Verona, Italy, 5Ospedali Riuniti di Ancona, Ancona, Italy, 6, ASST Spedali Civili, Brescia, Italy, 7Ospedale Niguarda, Milan, Italy, 8University of Genova, Genova, Italy, 9Padua University Hospital, Padua, Italy, 10Humanitas Gavazzeni, Bergamo, Italy, 11University of Turin, Italy, 12University Hospital Città Salute e Scienza, Turin, Italy
In acromegaly, 25–50% of patients respond inadequately to conventional somatostatin analog (SRL) therapy. In these cases, current guidelines recommend to increase frequency or dose of SRLs, but most of data have been provided by studies performed with octreotide LAR, whereas evidence on lanreotide autogel (LAN-ATG) is still scanty and anedoctal. This study evaluated the biochemical efficacy and safety of high-dose (HD) and high-frequency (HF) of LAN-ATG in patients with acromegaly. A 24-week prospective, multicenter, randomized, open-label trial was conducted in 30 acromegaly patients with partial biochemical response to conventional SRLs. Patients were randomized to HF (120 mg/21 days; 15 cases) or HD (180 mg/28 days; 15 cases) LAN-ATG. Primary end-point was normalization of serum IGF-I values [i.e., values below 1.2 of ULN for age and sex] and reduction in random GH values below 1.0 µg/l after 24 weeks of treatment. Secondary end-points included reduction in serum IGF-I and GH, differences in biochemical response and serum lanreotide values between HF-LAN-ATG and HF-LAN-ATG, and safety/tolerability evaluations.
The intention-to-treat (ITT) analysis was performed on 29 patients (14 randomized to HF-LAN-ATG and 15 randomized to HD-LAN-ATG), since one patient (in HF group) received only one drug dose afterward treatment was voluntarily withdrawn due to a side-effect (i.e., thoracic pain without evidence of ischemic heart disease) which was not known to be associated to LAN-ATG. In the whole ITT population, serum IGF-I decreased significantly during the 24-week study period (p=0.007) with more profound effects in the HD vs HF arm (p= p=0.039). Nine patients (31.0%; CI 95% 15.3%-50.8%) showed normal serum IGF-I at the end of follow-up (p=0.016 vs. baseline), without significant difference between HF and HD groups (p=0.59). Serum GH values did not change significantly (p=0.22) during the 24-week study period and 4 patient (13.8%, C.I.95% 3.9%-31.7%) showed random GH values below 1 µg/l at the end of follow-up. Three patients (10.3%, C.I.95% 2.2-27.4%) achieved full biochemical control of acromegaly (p=0.50 vs. baseline) by treatment. A significant increase in serum lanreotide values was observed during 24 weeks of treatment (p=0.002) and the end of follow-up lanreotide values were not significantly different between HF and HD groups (5.4 ng/ml, IQ 5.2-7.4 vs. 8.6 ng/ml, IQ 5.8-9.2; p=0.07). At 12-24 weeks, serum lanreotide values were significantly correlated with variation in serum IGF-I (r: -0.39; p=0.04). Overall, 19 patients (63.3%) experienced one or more adverse events mostly concerning gastrointestinal disturbances, without differences between HF- and HD-LAN-ATG.
In conclusion, HF- and HD- LAN-ATG regimens are effective in normalizing IGF-I values in a subset of patients with active acromegaly inadequately controlled with long-term conventional SRL therapy.
Disclosure: AG: Ad Hoc Consultant, Ipsen, Ad Hoc Consultant, Novartis Pharmaceuticals, Ad Hoc Consultant, Pfizer, Inc.. GM: Ad Hoc Consultant, Ipsen, Ad Hoc Consultant, Novartis Pharmaceuticals. SC: Advisory Group Member, Novartis Pharmaceuticals, Advisory Group Member, Pfizer, Inc., Advisory Group Member, Italfarmaco, Editor, Ipsen, Editor, Ferring Pharmaceuticals. PM: Speaker, Ipsen. MT: Coinvestigator, Novartis Pharmaceuticals. Nothing to Disclose: RC, GA, GB, RC, DF, AMF, FM, MM, EG