ECE2018 Guided Posters Pituitary Clinical (12 abstracts)
Predictors of response to long-acting pasireotide in patients with Cushing’s disease during a Phase III study
Przemysław Witek 1 , Beverly M K Biller 2 , André Lacroix 3 , Richard Feelders 4 , Yiming Li 5 , Eliza B Geer 6 , Thierry Brue 7 , Shoba Ravichandran 8 , Libuse Tauchmanova 9 , Michael Roughton 9 & Stephan Petersenn 10
1Department of Gastroenterology, Endocrinology and Internal Diseases, Military Institute of Medicine, Warsaw, Poland; 2Neuroendocrine Clinical Center, Massachussetts General Hospital, Boston, Massachussetts, USA; 3Division of Endocrinology, Centre hospitalier de l’Université de Montréal, Montreal, Quebec, Canada; 4Department of Internal Medicine, Endocrine Section, Erasmus Medical Center, Rotterdam, The Netherlands; 5Department of Endocrinology and Metabolism, Huashan Hospital, Fudan University, Shanghai, China; 6Multidisciplinary Pituitary and Skull Base Tumor Center, Memorial Sloan Kettering Cancer Center, New York, New York, USA; 7Hôpital de la Conception, Marseille, France; 8Novartis Pharmaceuticals Corporation, East Hanover, New Jersey, USA; 9Novartis Pharma AG, Basel, Switzerland; 10ENDOC Center for Endocrine Tumors, Hamburg, Germany.
Introduction: Long-acting pasireotide reduced urinary free cortisol (UFC) in most patients with Cushing’s disease (CD) during a large Phase III study (Lacroix et al. Lancet Diabetes Endocrinol 2018). The analyses presented here explored the impact of baseline characteristics on response to long-acting pasireotide.
Methods: 150 patients with persistent, recurrent or de novo CD and mean UFC (mUFC; from three 24-hour samples collected over 2 weeks) of 1.5–5xULN were randomized to monthly pasireotide 10 mg/30 mg. Dose up-titration was permitted at month (M) 4, M7, M9, and/or M12. Primary endpoint: mUFC≤ULN at M7. As response rates were similar between dose groups, data were pooled for the current analyses.
Results: 41.3% (n=62/150) of patients achieved mUFC≤ULN at M7 (responders). Of patients with mUFC≤ULN at M3, 73.3% (n=33/45) were responders at M7, compared with 27.6% (n=29/105) of those with mUFC>ULN at M3. Baseline mean [S.D.] mUFC was numerically lower in responders than in non-responders (424.1 [308.8] vs 502.3 [284.1] nmol/24 h; P=0.11). Other baseline mean (S.D.) values in responders and non-responders were, respectively: serum cortisol, 571.3 (184.5) and 575.1 (207.5) pmol/l; late-night salivary cortisol, 12.2 (13.7) and 9.3 (6.6) nmol/l; maximum tumour diameter, 9.9 (4.5) and 9.8 (6.8) mm. Higher response rates were seen in patients with lower baseline mUFC; response rates were similar in other subgroups analysed (Table).
Response rate by baseline characteristic
| n | Response rate, % (95%CI) | |
| Surgical status | ||
| No prior surgery | 27 | 40.7 (22.4–61.2) |
| Prior surgery | 123 | 41.5 (32.7–50.7) |
| Sex | ||
| Male | 32 | 40.6 (23.7–59.4) |
| Female | 118 | 41.5 (32.5–51.0) |
| Age quartile (range, years) | ||
| Q1 (18–27) | 31 | 32.3 (16.7–51.4) |
| Q2 (28–36) | 42 | 40.5 (25.6–56.7) |
| Q3 (37–46) | 38 | 50.0 (33.4–66.6) |
| Q4 (48–71) | 39 | 41.0 (25.6–57.9) |
| mUFC quartile (range, nmol/24 h) | ||
| Q1 (44.7–272.5) | 37 | 54.1 (36.9–70.5) |
| Q2 (277.6–392.5) | 38 | 47.4 (31.0–64.2) |
| Q3 (400.8–603.9) | 37 | 32.4 (18.0–49.8) |
| Q4 (607.3–1670.0) | 38 | 31.6 (17.5–48.7) |
| Adenoma size* | ||
| Microadenoma | 68 | 35.3 (24.1–47.8) |
| Macroadenoma | 49 | 49.0 (34.4–63.7) |
| Non-visible | 29 | 44.8 (26.4–64.3) |
| Maximum tumour diameter quartile (range, mm) | ||
| Q1 (3–5) | 22 | 36.4 (17.2–59.3) |
| Q2 (6–8) | 35 | 42.9 (26.3–60.6) |
| Q3 (9–11) | 27 | 29.6 (13.8–50.2) |
| Q4 (12–54) | 33 | 51.5 (33.5–69.2) |
| *By maximum diameter (microadenoma>0–<10 mm; macroadenoma≥10 mm) | ||
Conclusion: Lower baseline mUFC and early control of mUFC after initiation of long-acting pasireotide were associated with higher response rates at M7.
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