Coadministration of lanreotide Autogel(R) and pegvisomant normalizes IGF1 levels and is well tolerated in patients with acromegaly partially controlled by somatostatin analogs alone.

Objective: Evaluate efficacy and safety of coadministered lanreotide Autogel® (LA) 120 mg/month and pegvisomant 40-120 mg/week in acromegaly. Design: 28-week, multicenter, open-label, single-arm sequential study. Methods: Patients (n = 92) biochemically uncontrolled on somatostatin analogs (SSAs) or using pegvisomant monotherapy entered a 4-month run-in taking LA 120 mg/month. Patients uncontrolled after run-in (n = 57) entered the 28-week coadministration period, receiving LA 120 mg/month plus pegvisomant (60 mg once weekly, adapted every 8 weeks based on insulin-like growth factor 1 [IGF1] levels to 40-80 mg once weekly, or 40 or 60 mg twice weekly). Results: 33 (57.9%) patients normalized IGF1 following coadministration (P < 0.0001 versus 30% minimum clinically relevant); median pegvisomant dose in normalized patients: 60 mg/week. IGF1 normalized at any time during coadministration in 45 (78.9%) patients (P < 0.0001) with median pegvisomant dose 60 mg/week. Being nondiabetic (OR: 4.65) and older (OR, upper versus lower quartile: 3.40) showed increased likelihood of normalization. Symptom reduction was greatest for arthralgia (-0.6±1.6) and soft tissue swelling (-0.6±1.8). Five patients reported treatment-emergent adverse events causing treatment withdrawal: three serious (treatment-related: thrombocytopaenia, urticaria; not treatment-related: abdominal pain/vomiting) and two nonserious (hepatotoxicity and cytolytic hepatitis, both elevating alanine aminotransferase to >5×ULN with normalization after withdrawal). Conclusions: In patients partially controlled by SSAs, LA 120 mg/month plus pegvisomant normalized IGF1 in 57.9% of patients after 7 months, at a median effective pegvisomant dose of 60 mg/week, and 78.9% at any time. In these patients, results suggest a pegvisomant-sparing effect versus daily pegvisomant monotherapy.