Predictors of response to long-acting pasireotide in patients with Cushing

Przemyslaw Witek; Beverly M K Biller; Andre Lacroix; Richard Feelders; Yiming Li; Eliza B Geer; Thierry Brue; Shoba Ravichandran; Libuse Tauchmanova; Michael Roughton; Stephan Petersenn

doi:10.1530/endoabs.56.GP205

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Endocrine Abstracts (2018) 56 GP205 | DOI: 10.1530/endoabs.56.GP205

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

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Author affiliations

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

**Table 1**
	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.