Pegvisomant and Pasireotide LAR as second line therapy in acromegaly: clinical effectiveness and predictors of response

in European Journal of Endocrinology
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  • 1 Pituitary Unit, Department of Endocrinology and Diabetes, Fondazione Policlinico Universitario A. Gemelli, IRCCS, Rome, Italy
  • 2 Dipartimento di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, Rome, Italy
  • 3 Department of Radiology, Istituto Dermatopatico dell’Immacolata, IRCCS, Rome, Italy
  • 4 Istituto di Radiologica, Università Cattolica del Sacro Cuore, Rome, Italy
  • 5 Department of Neurosurgery, Fondazione Policlinico Universitario A. Gemelli, IRCCS, Università Cattolica del Sacro Cuore, Rome, Italy
  • 6 Department di Pathology, Fondazione Policlinico Universitario A. Gemelli, IRCCS, Rome, Italy
  • 7 Istitute of Pathology, Università Cattolica del Sacro Cuore, Rome, Italy
  • 8 Endocrinology Vita-Salute San Raffaele University, IRCCS, San Raffaele Hospital, Milano, Italy
  • 9 Departments of Medicine (Endocrinology) and Neurological Surgery, and Pituitary Center, Oregon Health & Science University, Portland, Oregon, USA

Correspondence should be addressed to L De Marinis; Email: Laura.Demarinis@unicatt.it
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Background

The treatment of acromegaly resistant to first-generation somatostatin receptor ligands (SRLs) is often difficult. Pegvisomant and Pasireotide LAR are mostly used in these subset of patients, as second line therapies. Choice of the type of second line therapies is difficult, since predictors of response are still unclear, impairing personalized therapy. We aimed to investigate predictors of response to Pegvisomant and Pasireotide LAR.

Methods

Seventy-four acromegaly patients entered this observational, cross-sectional and retrospective study if (i) resistant to high dose first-generation SRLs and (ii) treated with Pegvisomant and Pasireotide LAR for at least 12 consecutive months. Patients treated with radiotherapy in the previous 10 years were excluded.

Results

Fourty-one patients were treated with Pegvisomant and 33 with Pasireotide LAR. At the end of the study, acromegaly was controlled in 35 patients treated with Pegvisomant (85.4%) and in 23 treated with Pasireotide LAR (69.7%). In this cohort, a poor Pegvisomant response and a shorter progression free time were observed in cases with tumor extension to the third ventricle (P = 0.004, HR: 1.6, 95%CI: 1.2–4.6), with a Ki67-Li >4% (P = 0.004, HR: 3.49, 95%CI: 1.4–4.0) and with pre-treatment IGF-I >3.3×ULN (P=0.03, HR: 1.3, 95%CI: 1.1–6.0). A poor Pasireotide LAR response and a shorter progression free time were observed in cases with tumor extension to the third ventricle (P=0.025, HR: 1.6 95%CI: 1.4–3.4), pre-treatment IGF-I >2.3×ULN (P=0.049, HR: 2.4, 95%CI: 1.4–8.0), absent/low SST5 membranous expression (P=0.023 HR: 4.56 95%CI: 1.3–6.4) and in patients carried the d3-delated GHR isoform (P=0.005, HR: 11.37, 95%CI: 1.3–20.0).

Conclusion

Molecular and clinical biomarkers can be useful in predicting the responsiveness to Pegvisomant and Pasireotide LAR.

 

     European Society of Endocrinology

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