ECE2020 Audio ePoster Presentations Pituitary and Neuroendocrinology (217 abstracts)
Sustained response to treatment with oral octreotide capsules: Results from the phase 3, randomized, double blind, placebo-controlled optimal study
Susan Samson 1 , Lisa Nachtigall 2 , Maria Fleseriu 3 , Agata Baldys Waligorska 4 , Mojca Jensterle 5 , Ehud Ur 6 , Mark E Molitch 7 , William Ludlam 8 , Gary Patou 8 , Asi Haviv 8 , Nienke Biermasz 9 , Laurence Kennedy 10 , Shlomo Melmed 11 & Christian J Strasburger 12
1Baylor College of Medicine; 2MGH Neuroendocrine and Pituitary Center; 3Oregon Health & Science University, Portland, United States; 4Andrzej Frycz Modrzewski Krakow University; 5Department of Endocrinology, Diabetes and Metabolic Diseases, University Medical Centre Ljubljana; 6UBC; 7Northwestern University, Evanston, United States; 8Chiasma; 9LUMC – Endocrinology and metabolisme; 10Cleveland Clinic Foundation; 11Cedars Sinai Medical Center; 12Charité Campus Mitte
Background: Patients with acromegaly responding to injectable somatostatin receptor ligands (SRL) are often treated for decades without deterioration of biochemical response (except for routine fluctuations in IGF-I control), unless there are changing clinical circumstances such as persistent or recurrent tumor growth. Oral octreotide capsules (OOC) have been formulated as a potential therapy for acromegaly and the safety and efficacy was evaluated in the CHIASMA OPTIMAL pivotal study. In CHIASMA OPTIMAL, 58% of patients receiving OOC met the primary endpoint and maintained their baseline response levels (IGF–I ≤ 1 ×ULN) vs 19% of patients receiving placebo (P = 0.008). At the end of treatment, mean IGF-I levels of the OOC treatment group were maintained within normal range in all patients and 75% of patients in this group maintained IGF-I levels ≤ 1.1 ×ULN. This analysis describes the durability of OOC treatment response (Samson et al. ENDO 2020).
Methods: Patients were ≥ 18 years of age, had evidence of active disease, and an average IGF-I ≤ 1.0 × ULN receiving a stable dose of SRL injections (≥ 3 months). Patients were randomized to OOC (40 mg/day; n = 28) or placebo (n = 28) for 36 weeks. Dose was titrated to 60 or 80 mg OOC (or placebo) through week 24 at investigator discretion based on increased IGF-I levels and/or worsening acromegaly signs/symptoms. Patients not responding (OOC or placebo) could revert to prior injectable SRL therapy if they met the predefined withdrawal criteria (i.e., IGF–I ≥ 1.3 × ULN for 2 consecutive visits on the highest dose and exacerbation of clinical signs/symptoms). The primary endpoint was proportion of patients maintaining biochemical response, defined as IGF–I ≤ 1.0 × ULN (average: weeks 34 and 36). Patients who discontinued oral treatment (OOC or placebo) were considered non-responders regardless of clinical response at the time of discontinuation (non-response imputation or WOCF). For this analysis, the proportion of week 24 responders (IGF–I ≤ 1.0 × ULN) in the OOC group who maintained their response at the end of study is presented.
Results: Analyzing a subgroup of 12 patients who were responders (IGF-I ≤ 1.0 × ULN) to OOC when assessed at week 24 (end of dose titration phase) in the OOC treatment arm, 11 of these 12 patients had a sustained or durable response to end of treatment at 9 months (91.7%).
Conclusion: Efficacy was durable in CHIASMA OPTIMAL. This suggests that patients who respond to OOC with maintained normal IGF-I may potentially be maintained on treatment without deterioration in IGF-I control. Longer-term extension studies are ongoing.
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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