Maintenance of Acromegaly Control in Patients Switching From Injectable Somatostatin Receptor Ligands to Oral Octreotide

Abstract

Purpose The Phase 3 CHIASMA OPTIMAL trial (NCT03252353) evaluated efficacy and safety of oral octreotide capsules (OOC) in patients with acromegaly who previously demonstrated biochemical control while receiving injectable somatostatin receptor ligands (SRLs). Methods In this double-blind study, patients (N=56) stratified by prior SRL dose were randomized 1:1 to OOC or placebo for 36 weeks. Primary endpoint was maintenance of biochemical control at end of treatment (mean IGF-I ≤1.0 x ULN; weeks 34 and 36). Time to loss of IGF-I response and proportion requiring reversion to injectable SRLs were assessed as broader control measures. Results Mean IGF-I were 0.80 and 0.97 x ULN for OOC and 0.84 and 1.69 x ULN for placebo, at baseline and end of treatment, respectively. Mean GH changed from 0.66 to 0.60 ng/mL for OOC and 0.90 to 2.57 ng/mL for placebo. Normalization of IGF-I levels (≤1.0 x ULN) was maintained in 58.2% for OOC versus 19.4% for placebo (P=0.0079); GH levels were maintained (<2.5 ng/mL) in 77.7% for OOC versus 30.4% for placebo (P=0.0007). Median time to loss of response (IGF-I >1.0 or ≥1.3 x ULN definitions) for patients receiving placebo was 16 weeks; for patients receiving OOC, it was not reached for both definitions during the 36-week trial (P<0.0001). Of the patients in the OOC group, 75% completed the trial on oral therapy. The OOC safety profile was consistent with previous SRL experience. Conclusions OOC may be an effective therapy for patients with acromegaly who previously were treated with injectable SRLs.

A Pituitary Society update to acromegaly management guidelines

“… OOC are suitable for patients who have demonstrated complete or partial biochemical response on injectable octreotide or lanreotide. (HQ, SR) Rationale: As octreotide and lanreotide have similar efficacy, patients who have responded to these injectable agents are candidates for OOC therapy, and results of the OPTIMAL study demonstrate that biochemically controlled patients (IGF-I ≤ 1.0 × ULN) on stable doses of injectable octreotide or lanreotide maintain response to OOC [ 4 ]. There are no data regarding efficacy of switching patients from pasireotide LAR to OOC.There are no data on the use of OOC as primary medical therapy in SRL-naïve patients.…”

“…Rationale: The 40 mg/day dose is the approved initiation dose [ 7 ]. Most responders in the OPTIMAL study up-titrated to 60 mg/d or 80 mg/d by study end, and all patients enrolling in the open label extension study were reinitiated at the 60 mg/d dose [ 4 , 8 ] OOC should be initiated at the time of the previously scheduled SRL injection. (HQ, SR) Rationale: In clinical trials, OOC was initiated at the time of the next SRL injection, i.e., at the end of the once-monthly injection period [ 4 , 9 ].…”

Results from ACROCOVID: an international survey on the care of acromegaly during the COVID-19 era

“…In fact, use of self-administered SSAs without the need for house visits from health professionals or even hospital visits for injection were demonstrated to be of increased importance during the pandemic and, likely, also for future clinical management [40,41]. In this context, the possibility of orally administered SSAs [42][43][44] may have important clinical implications for simplified management of wellcontrolled disease in emergency situations, such as the COVID-19 pandemic.…”

Novel therapies for acromegaly

“…Oral octreotide was also evaluated in a 9-month phase 3 double-blind, randomized, placebo-controlled, multicenter study designed to evaluate efficacy and safety of octreotide capsule in acromegaly patients who demonstrated biochemical control on injectable SRL treatments ( 46 ). In this trial, 56 patients with acromegaly previously controlled (IGF-I ≤ 1.0 × ULN based on the average of two assessments) with injectable fg-SRL (on a stable dose for ≥3 months of therapy and using it for ≥6 months) were switched for oral octreotide or placebo.…”

“…In this trial, 56 patients with acromegaly previously controlled (IGF-I ≤ 1.0 × ULN based on the average of two assessments) with injectable fg-SRL (on a stable dose for ≥3 months of therapy and using it for ≥6 months) were switched for oral octreotide or placebo. Normalization of IGF-I levels was maintained in 58% of patients treated with oral octreotide in comparison with 19% in the placebo group ( P = 0.0079) ( 46 ). On June 26, 2020, FDA approved oral octreotide capsules as the first oral SRL for long-term maintenance treatment in patients with acromegaly who have responded to and tolerate treatment with injectable SRLs.…”