ECE2016 Guided Posters Pituitary - Clinical (10 abstracts)
Introduction: Although biochemical markers of acromegaly disease activity, including GH and IGF1, may fluctuate from day-to-day, biochemical treatment response in clinical trials is generally monitored using single-point analyses. Accordingly, longitudinal evaluations may assess patient status more accurately. In a phase 3 trial, oral octreotide capsules (OOC) demonstrated sustained composite endpoint GH and IGF1 response for ≤13 months in 151 patients with acromegaly previously managed with somatostatin analog injections (IGF1<1.3× ULN and GH<2.5 ng/ml). Here we report longitudinal IGF1 and GH analyses from this trial.
Methods: Trial design comprised core (dose escalation [DE] + fixed dose [FD]; ≤7 months) and extension (≤13 months) periods. IGF1 was assessed monthly; mean integrated GH was assessed upon up-titration and at the beginning and end of each period. For the primary study endpoint, response was determined by a composite including IGF1 and GH at End-of-Treatment (EoT). In this post hoc analysis, longitudinal IGF1 and GH are expressed as time-weighted average (TWA) incorporating all measurements; response is defined as a composite including TWA IGF1<1.3× ULN and TWA GH<2.5 ng/ml.
Results: At end of core period, 108/151 patients (72%) achieved response by TWA, vs 98/151 (65%) per initial EoT composite endpoint analysis. Of patients who entered FD (n=110), 88 (80%) completed the core period (7 months) and achieved response by TWA, vs 82/110 (75%) per EoT analysis. Of patients who entered FD as responders by protocol (n=91), 86 (95%) maintained TWA response through extension (≤13 months), vs 77/91 (85%) per EoT analysis.
Conclusions: Based on a composite using TWA IGF1 and TWA GH, OOC demonstrated a greater response vs the single-point analysis at EoT. Analyses incorporating all evaluations may provide more accurate and clinically meaningful assessments of overall treatment response than single-point evaluations. Therefore, ongoing studies using OOC evaluate response using all evaluations.