Oral octreotide capsules for acromegaly treatment: application of clinical trial insights to real-world use

Figures & data

Table 1. Medical therapies for acromegaly [1].

Therapy	Dose	Mechanism of Action	Specific Conditions for Prescription (if applicable)
Cabergoline	up to 2.5–5 mg/week oral administration	Acts on dopamine-2 receptors	IGF-1 <1.5–2 × ULN (most experts suggest <1.5)
Octreotide Octreotide LAR Lanreotide	50 μg subcutaneous injection, three times daily 10–40 mg intramuscular injection every 4 weeks 60–120 mg deep subcutaneous injection every 4–8 weeks	Signal through SST receptors to suppress growth hormone secretion and control somatotroph proliferation	First-line postoperative medical therapy in most patients and primary medical therapy in patients who are not suitable candidates for surgery or not willing to have surgery
Oral octreotide capsules	40–80 mg/day		Patients controlled on injectable octreotide/lanreotide who have injection-related treatment burden
Pasireotide LAR	40–60 mg intramuscular injection every 4 weeks		Second-line or third-line medical therapy in most patients, but first-line in select patients with predicted resistance to octreotide/lanreotide, adenoma growth or headache not responsive to octreotide/lanreotide, or non-response or intolerance to pegvisomant or octreotide/lanreotide – pegvisomant combination
Pegvisomant	10–30 mg/day, up to 40 mg/day, subcutaneous injection	Competitively blocks GH receptor signaling	Second-line medical therapy in most patients and first-line medical therapy in select patients with predicted resistance to treatment with octreotide/lanreotide and no adenoma growth concern
SRL-pegvisomant			Treatment with combined octreotide/lanreotide – pegvisomant is favored if tumor volume is large, patient has headache, control on SRL is inadequate, or diabetes is inadequately controlled with SRL or pegvisomant monotherapy; treatment with combined pasireotide LAR – pegvisomant is often third-line medical therapy and is favored if symptoms are relieved with SRL but patient is inadequately controlled on octreotide/lanreotide – pegvisomant, if large adenoma volume is non-responsive to octreotide/lanreotide – pegvisomant, or if patient does not have diabetes
SRL-cabergoline			Mildly elevated IGF-1 concentrations (<2 × ULN) on SRL monotherapy
Cabergoline-pegvisomant			Rarely used, data are scarce [41]

LAR, long-acting release; SST, somatostatin; ULN, upper limit of normal.

Table 2. Common gastrointestinal adverse events associated with acromegaly and currently approved somatostatin receptor ligands for acromegaly.

Therapy Type	Clinical Trial	Diarrhea	Abdominal pain or discomfort	Nausea	Flatulence	Constipation	Vomiting	Dyspepsia
Placebo [36]	OPTIMAL NCT03252353 N = 28^a	6 (21.4)	3 (10.7)	3 (10.7)	–	–	0	1 (3.6)
iSRLs [30]	MPOWERED NCT02685709 N = 37^b	5 (14)	2 (5)	1 (3)	6 (16)	3 (8)	^–	–
Octreotide (LAR) [35]	NCT00600886 N = 182^c	81 (45.0)	40 (22.2)	39 (21.7)	–	–	^–	–
Pasireotide (LAR) [35]	NCT00600886 N = 176^c	70 (39.3)	32 (18.0)	24 (13.5)	–	–	–	–
Octreotide capsules [30,36]	OPTIMAL NCT03252353 N = 28^a	8 (28.6)	4 (14.3)	6 (21.4)	–	–	4 (14.3)	3 (10.7)
	MPOWERED NCT02685709 N = 55^b	4 (7)	3 (6)	9 (16)	10 (18)	1 (2)	–	–

Data are n (%). AE, adverse event; iSRL, injectable somatostatin receptor ligand; LAR, long-acting release; MedDRA, Medical Dictionary for Regulatory Activities; TEAE, treatment-emergent adverse event.

^aTEAEs were defined as all AEs that occurred after random assignment (i.e., date of onset was on or after the date of random assignment) and on or before the end of treatment (last dose of blinded study drug) in the double-blind, placebo-controlled period. A patient could be counted only once within each category. AEs were coded using MedDRA v18.1.

^bTEAEs were defined as AEs with an onset on or after study drug initiation and before the end of treatment in the randomized treatment phase. AEs were coded using MedDRA v18.1.

^cTwo patients randomized to the octreotide LAR treatment arm received pasireotide LAR in error. These two patients are included in the pasireotide LAR treatment arm for the purposes of the safety analysis.

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