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De-escalation treatment with pasireotide for acromegaly: a long-term experience

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Abstract

Introduction

Pasireotide long-acting release (LAR) is approved for second-line treatment of acromegaly. Starting pasireotide LAR 40 mg every 4 weeks is recommended and then up-titrate to 60 mg monthly in case of IGF-I uncontrolled levels. We present three patients treated with a de-escalation approach with pasireotide LAR.

Case 1

A 61-year-old female diagnosed with resistant acromegaly was treated with pasireotide LAR 60 mg every 28 days. When IGF-I reached the lower age range, therapy was decreased to pasireotide LAR 40 mg and then to 20 mg. In 2021 and 2022, IGF-I value remained within the normal range.

Case 2

A 40-year-old female diagnosed with resistant acromegaly underwent three neurosurgeries. In 2011, she was enrolled in the PAOLA study and assigned to pasireotide LAR 60 mg. Due to IGF-I overcontrol and radiological stability, therapy was downscaled to 40 mg in 2016 and to 20 mg in 2019. The patient developed hyperglycemia, which was treated with metformin.

Case 3

A 37-year-old male diagnosed with resistant acromegaly was treated with pasireotide LAR 60 mg in 2011. In 2018, therapy was decreased to 40 mg due to IGF-I overcontrol and in 2022 to 20 mg. He developed hyperglycemia, but HbA1c values remained under 48 nmol/L for 7 years.

Conclusion

De-escalation treatment with pasireotide LAR may allow a greater proportion of patients to achieve control of acromegaly, particularly in selected cases of clinically aggressive acromegaly potentially responsive to pasireotide (high IGF-I values, invasion of the cavernous sinuses, partial resistance to first-line somatostatin analogues and positive expression of somatostatin receptor 5). Another benefit may be IGF-I oversuppression overtime. The major risk seems to be hyperglycemia.

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References

  1. S. Petersenn, J. Schopohl, A. Barkan, P. Mohideen, A. Colao, R. Abs, A. Buchelt, Y.-Y. Ho, K. Hu, A.J. Farrall, S. Melmed, B.M.K. Biller, Pasireotide (SOM230) demonstrates efficacy and safety in patients with acromegaly: a randomized, multicenter, phase II trial. J. Clin. Endocrinol. Metab. 95(6), 2781–2789 (2010). https://doi.org/10.1210/jc.2009-2272

    Article  CAS  PubMed  Google Scholar 

  2. A. Colao, M.D. Bronstein, T. Brue, L. de Marinis, M. Fleseriu, M. Guitelman, G. Raverot, I. Shimon, J. Fleck, P. Gupta, A.M. Pedroncelli, M.R. Gadelha, Pasireotide for acromegaly: long-term outcomes from an extension to the Phase III PAOLA study. Eur. J. Endocrinol. 182(6), 583 (2020). https://doi.org/10.1530/EJE-19-0762

  3. A. Akirov, A. Gorshtein, I. Dotan, N.S. Khazen, Y. Pauker, M. Gershinsky, I. Shimon, Long-term safety and efficacy of long-acting pasireotide in acromegaly. Endocrine 74(2), 396–403 (2021). https://doi.org/10.1007/s12020-021-02782-2

    Article  CAS  PubMed  Google Scholar 

  4. S. Chiloiro, A. Giampietro, F. Mirra, F. Donfrancesco, T. Tartaglione, P.P. Mattogno, F. Angelini, L. Liverana, M. Gessi, A. Carmelo, G. Rindi, A. Giustina, M. Fleseriu, A. Pontecorvi, L. de Marinis, A. Bianchi, Pegvisomant and Pasireotide LAR as second line therapy in acromegaly: clinical effectiveness and predictors of response. Eur. J. Endocrinol. 184(2), 217–229 (2021). https://doi.org/10.1530/EJE-20-0767

  5. G. Raverot, P. Burman, A. McCormack, A. Heaney, S. Petersenn, V. Popovic, J. Trouillas, O.M. Dekkers, European Society of Endocrinology clinical practice guidelines for the management of aggressive pituitary tumours and carcinomas. Eur. J. Endocrinol. 178(1), G1–G24 (2018). https://doi.org/10.1530/EJE-17-0796

    Article  CAS  PubMed  Google Scholar 

  6. S. Melmed, M.D. Bronstein, P. Chanson, A. Klibanski, F.F. Casanueva, J.A.H. Wass, C.J. Strasburger, A. Luger, D.R. Clemmons, A. Giustina, A Consensus Statement on acromegaly therapeutic outcomes. Nat. Rev. Endocrinol. 14(9), 552–561 (2018). https://doi.org/10.1038/s41574-018-0058-5

    Article  PubMed  PubMed Central  Google Scholar 

  7. A. Giustina, G. Barkhoudarian, A. Beckers, A. Ben-Shlomo, N. Biermasz, B. Biller, C. Boguszewski, M. Bolanowski, J. Bollerslev, V. Bonert, M.D. Bronstein, M. Buchfelder, F. Casanueva, P. Chanson, D. Clemmons, M. Fleseriu, A.M. Formenti, P. Freda, M. Gadelha, E. Geer, M. Gurnell, A.P. Heaney, K.K.Y. Ho, A.G. Ioachimescu, S. Lamberts, E. Laws, M. Losa, P. Maffei, A. Mamelak, M. Mercado, M. Molitch, P. Mortini, A.M. Pereira, S. Petersenn, K. Post, M. Puig-Domingo, R. Salvatori, S.L. Samson, I. Shimon, C. Strasburger, B. Swearingen, P. Trainer, M.L. Vance, J. Wass, M.E. Wierman, K.C.J. Yuen, M.C. Zatelli, S. Melmed, Multidisciplinary management of acromegaly: a consensus. Rev. Endocr. Metab. Disord. 21(4), 667–678 (2020). https://doi.org/10.1007/s11154-020-09588-z

    Article  PubMed  PubMed Central  Google Scholar 

  8. E.C. Coopmans, A. Muhammad, A.J. van der Lely, J.A.M.J.L. Janssen, S.J.C.M.M. Neggers, How to position Pasireotide LAR treatment in acromegaly. J. Clin. Endocrinol. Metab. 104(6), 1978–1988 (2019). https://doi.org/10.1210/jc.2018-01979

    Article  PubMed  Google Scholar 

  9. A. Muhammad, E.C. Coopmans, F. Gatto, S.E. Franck, J.A.M.J.L. Janssen, A.J. van der Lely, L.J. Hofland, S.J.C.M.M. Neggers, Pasireotide responsiveness in acromegaly is mainly driven by somatostatin receptor subtype 2 expression. J. Clin. Endocrinol. Metab. 104(3), 915–924 (2019). https://doi.org/10.1210/jc.2018-01524

    Article  PubMed  Google Scholar 

  10. F. Gatto, R.A. Feelders, S.E. Franck, P.M. van Koetsveld, F. Dogan, J.M. Kros, S.J.C.M.M. Neggers, A.J. van der Lely, S.W.J. Lamberts, D. Ferone, L.J. Hofland, In vitro head-to-head comparison between octreotide and pasireotide in GH-secreting pituitary adenomas. J. Clin. Endocrinol. Metab. 102(6), 2009–2018 (2017). https://doi.org/10.1210/jc.2017-00135

    Article  PubMed  Google Scholar 

  11. M. Chalabi, C. Duluc, P. Caron, D. Vezzosi, J. Guillermet-Guibert, S. Pyronnet, C. Bousquet, Somatostatin analogs: does pharmacology impact antitumor efficacy? Trends Endocrinol. Metab. 25(3), 115–127 (2014). https://doi.org/10.1016/j.tem.2013.11.003

    Article  CAS  PubMed  Google Scholar 

  12. M. Stelmachowska-Banaś, I. Czajka-Oraniec, A. Tomasik, W. Zgliczyński, Real-world experience with pasireotide-LAR in resistant acromegaly: a single center 1-year observation. Pituitary 25(1), 180–190 (2022). https://doi.org/10.1007/s11102-021-01185-w

    Article  CAS  PubMed  Google Scholar 

  13. S. Chiloiro, D. Costa, R. Lauretta, V. Mercuri, E. Sbardella, I. Samperi, M. Appetecchia, A. Bianchi, A. Giampietro, P. Gargiulo, A.M. Isidori, M. Poggi, A. Pontecorvi, De, L. Marinis, Partial response to first generation SSA guides the choice and predict the outcome of second line therapy in acromegaly. Endocrine 78(2), 343–353 (2022). https://doi.org/10.1007/s12020-022-03158-w

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. M. Volante, M.P. Brizzi, A. Faggiano, S. La Rosa, I. Rapa, A. Ferrero, G. Mansueto, L. Righi, S. Garancini, C. Capella, G. De Rosa, L. Dogliotti, A. Colao, M. Papotti, Somatostatin receptor type 2A immunohistochemistry in neuroendocrine tumors: a proposal of scoring system correlated with somatostatin receptor scintigraphy. Mod. Pathol. 20(11), 1172–1182 (2007). https://doi.org/10.1038/modpathol.3800954

    Article  CAS  PubMed  Google Scholar 

  15. I. Shimon, W. Saeger, L.E. Wildemberg, M.R. Gadelha, Somatotropinomas inadequately controlled with octreotide may over-respond to pasireotide: the importance of dose adjustment to achieve long-term biochemical control. Hormones (Athens) 16(1), 84–91 (2017). https://doi.org/10.14310/horm.2002.1722

    Article  PubMed  Google Scholar 

  16. S. Chiloiro, A. Giampietro, F. Visconti, L. Rossi, F. Donfrancesco, C.M. Fleseriu, F. Mirra, A. Pontecorvi, A. Giustina, M. Fleseriu, L. de Marinis, A. Bianchi, Glucose metabolism outcomes in acromegaly patients on treatment with pasireotide-LAR or pasireotide-LAR plus Pegvisomant. Endocrine 73, 658–666 (2021). https://doi.org/10.1007/s12020-021-02711-3

  17. S. Frara, F. Maffezzoni, G. Mazziotti, A. Giustina, Current and emerging aspects of diabetes mellitus in acromegaly. Trends Endocrinol. Metab. 27(7), 470–483 (2016). https://doi.org/10.1016/j.tem.2016.04.014

    Article  CAS  PubMed  Google Scholar 

  18. A. Giustina, A. Barkan, A. Beckers, N. Biermasz, B.M.K. Biller, C. Boguszewski, M. Bolanowski, V. Bonert, M.D. Bronstein, F.F. Casanueva, D. Clemmons, A. Colao, D. Ferone, M. Fleseriu, S. Frara, M.R. Gadelha, E. Ghigo, M. Gurnell, A.P. Heaney, K. Ho, A. Ioachimescu, L. Katznelson, F. Kelestimur, J. Kopchick, M. Krsek, S. Lamberts, M. Losa, A. Luger, P. Maffei, M. Marazuela, G. Mazziotti, M. Mercado, P. Mortini, S. Neggers, A.M. Pereira, S. Petersenn, M. Puig-Domingo, R. Salvatori, I. Shimon, C. Strasburger, S. Tsagarakis, A.J. van der Lely, J. Wass, M.C. Zatelli, S. Melmed, A consensus on the diagnosis and treatment of acromegaly comorbidities: an update. J. Clin. Endocrinol. Metab. 105(4), dgz096 (2020). https://doi.org/10.1210/clinem/dgz096

  19. P. Chanson, A. Arnoux, M. Mavromati, S. Brailly-Tabard, C. Massart, J. Young, M.L. Piketty, J.C. Souberbielle; VARIETE Investigators, Reference values for IGF-I serum concentrations: comparison of six immunoassays. J. Clin. Endocrinol. Metab. 101(9), 3450–3458 (2016). https://doi.org/10.1210/jc.2016-1257

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. S. Frara, G. Rodriguez-Carnero, A.M. Formenti, M.A. Martinez-Olmos, A. Giustina, F.F. Casanueva, Pituitary tumors centers of excellence. Endocrinol. Metab. Clin. North Am. 49(3), 553–564 (2020). https://doi.org/10.1016/j.ecl.2020.05.010

    Article  PubMed  Google Scholar 

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Author notes

  1. These authors contributed equally: Antonella Giampietro, Sara Menotti

Authors and Affiliations

  1. UOC Endocrinologia, Fondazione Policlinico A. Gemelli IRCCS, Università Cattolica del Sacro Cuore, 00168, Rome, Italy

    Antonella Giampietro, Sara Menotti, Sabrina Chiloiro, Alfredo Pontecorvi, Laura De Marinis & Antonio Bianchi

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  1. Antonella Giampietro
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  2. Sara Menotti
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  3. Sabrina Chiloiro
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  6. Antonio Bianchi
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Contributions

All authors contributed to the study conception and design. Material preparation, data collection and analysis were performed by A.G., S.M. and S.C. The first draft of the manuscript was written by S.M. and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Sabrina Chiloiro.

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Conflict of interest

A.G., S.M., S.C., L.D.M. and A.B. have served as investigator for clinical trials funded by Novartis, Pfizer, Ipsen and Crinetics. S.C. and A.B. received grants from Pfizer. S.C. won the 2022 Arrigo Recordati research grant. All the fees and honoraria are paid to their institution. They are members of Advisor Board for Novartis, Pfizer, Recordati.

Ethics approval

This study was performed in line with the principles of the Declaration of Helsinki. The approval was granted by the Ethics Committee of Università Cattolica del Sacro Cuore.

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Informed consent was obtained from all individual participants included in the study.

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Giampietro, A., Menotti, S., Chiloiro, S. et al. De-escalation treatment with pasireotide for acromegaly: a long-term experience. Endocrine 80, 505–510 (2023). https://doi.org/10.1007/s12020-023-03325-7

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