Oral acromegaly therapy maintains efficacy for most initial responders at 62 weeks
Nearly all responders to a 26-week course of oral octreotide maintained a biochemical response and symptomatic control of acromegaly at 62 weeks, according to data from the MPOWERED trial.
In an analysis of data from 92 participants who were responders to octreotide (Mycapssa, Chiasma) during a 26-week run-in phase, 50 of 55 adults continuing octreotide and all 37 participants randomly assigned to injectable somatostatin receptor ligands (SRLs) maintained a biochemical response to the agent for an additional 9 months.
“In patients previously responsive to both oral and injectable SRLs, oral octreotide was noninferior to injectable SRLs in maintaining biochemical response by use of the time-weighted average analysis, a clinically relevant measure of insulin-like growth factor I that represents an integrated measure of efficacy across time and can limit the noise associated with high variability in IGF-I,” Maria Fleseriu, MD, FACE, professor of medicine and neurological surgery and director of the Pituitary Center at Oregon Health & Science University in Portland and a Healio | Endocrine Today Co-editor, and colleagues wrote in a study published in The Lancet Diabetes & Endocrinology. “Sensitivity analyses showed that the primary efficacy analysis is robust and supports the conclusion of noninferiority.”
MPOWERED was a phase 3, randomized, open-label, active-controlled, multicenter trial of adults aged 18 to 75 years with acromegaly from 29 clinical sites in 10 countries. After screening, 146 participants were enrolled in a 6-month run-in period in which they received oral octreotide to establish an efficacious dose and determine the percentage of responders to the medication. At 26 weeks, 92 responders from the run-in phase were enrolled in a 36-week randomized treatment phase in which 55 were randomly assigned to continue receiving oral octreotide and 37 were randomly assigned to injectable somatostatin receptor ligands. The primary efficacy endpoint was a noninferiority assessment of the proportion of participants maintaining a biochemical response through the end of the trial. A biochemical response was defined as an IGF-I less than 1.3 times the upper limit of normal using a time-weighted average. Secondary endpoints included the number of reported active acromegaly symptoms during clinic visits, treatment satisfaction as measured by the Acromegaly Treatment Satisfaction Questionnaire, and work productivity as measured by the Work Productivity and Activity Impairment Questionnaire: Specific Health Problem.
Response maintained for most participants
For the primary endpoint, 50 of 55 participants receiving oral octreotide (95% CI, 44-53) and all 37 participants receiving injectable somatostatin receptor ligands (95% CI, 34-37) maintained biochemical response at 36 weeks. The overall number of active acromegaly symptoms was similar between the two groups, and there were no significant differences in acromegaly treatment satisfaction. Work productivity and activity impairment were also similar between the two groups in the randomized phase. However, in the run-in phase where all patients have been switched from injectable SRLs to oral octreotide, several symptoms, such as joint pain, extremity swelling, and fatigue were better controlled with oral octreotide compared with injectable SRLs.
The percentage of participants reporting treatment-emergent adverse events and serious adverse events was similar between the two groups. Most adverse events in both groups were gastrointestinal, including flatulence, nausea, diarrhea, abdominal pain and constipation.
“The oral octreotide safety profile is consistent with the known safety profile of injectable octreotide and the disease burden of acromegaly without injection site reactions,” the researchers wrote. “Although the trial did not monitor tumor control, no adverse events were reported that suggest any change in pituitary tumor status. Nausea was more frequently reported with oral octreotide versus injectable somatostatin receptor ligands, but overall numbers were small, and no participants discontinued treatment in the randomized treatment.”
More guidance on octreotide needed
In a commentary published in The Lancet Diabetes & Endocrinology, Maya B. Lodish, MD, MHSc, the Selna L. Kaplan Chair Distinguished Professorship in Pediatric Endocrinology/Diabetes, professor of pediatrics and chief of the division of pediatric endocrinology and diabetes at University of California, San Francisco, wrote that the proportion of people responding to oral octreotide in the trial may be an overestimation because those who were nonresponders during the 26-week run-in phase were excluded from randomization. She added that clinical guidance is needed on the practical use of oral octreotide, including strategies for identifying patients for the therapy and dose titration.
“We still lack data on the efficacy of oral octreotide capsules as primary medical therapy in patients with acromegaly,” Lodish told Healio. “In clinical practice, it would be ideal to be able to start a patient on an oral agent without having to give injections. An additional question that remains is what clinical factors correlate with likelihood of response to oral somatostatin analogues.
“We need a larger study looking at dose titration in oral octreotide as upfront therapy to understand individualized treatment factors that relate to response,” Lodish said.