Differences in the efficacy of second-line therapies on the biochemical control of acromegaly in patients with GH secreting pituitary neuroendocrine tumors (Pit-NETs) and GH and PRL cosecreting Pit-NETs

Castro Marta Araujo; Almudena Vicente; Fernando Cordido; Menendez Torre Edelmiro Luis; Eider Pascual-Corrales; Moreno Eva Venegas; Centeno Rogelio Garcia; Taibo Rocio Villar; Fernando Guerrero; Galiana Pablo Abellan; Hanzu Felicia A; Carmen Fajardo-Montanana; Cristina Novo; Rosa Camara; Aviles Perez Maria Dolores; Monica Marazuela; Betina Biagetti; Manel Puig-Domingo

doi:10.1530/endoabs.99.P524

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Endocrine Abstracts (2024) 99 P524 | DOI: 10.1530/endoabs.99.P524

ECE2024 Poster Presentations Pituitary and Neuroendocrinology (120 abstracts)

Differences in the efficacy of second-line therapies on the biochemical control of acromegaly in patients with GH secreting pituitary neuroendocrine tumors (Pit-NETs) and GH and PRL cosecreting Pit-NETs

Marta Araujo Castro ¹ , Almudena Vicente ² , Fernando Cordido ³ , Edelmiro Luis Menendez Torre ⁴ , Eider Pascual-Corrales ¹ , Eva Venegas Moreno ⁵ , Rogelio García Centeno ⁶ , Rocio Villar Taibo ⁷ , Fernando Guerrero ⁸ , Pablo Abellán Galiana ⁹ , Felicia A Hanzu ¹⁰ , Carmen Fajardo-Montañana ¹¹ , Cristina Novo ¹² , Rosa Camara ¹³ , Maria Dolores Aviles Perez ¹⁴ , Mónica Marazuela ¹⁵ , Betina Biagetti ¹⁶ & Manel Puig-Domingo ¹⁷

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¹Ramón y Cajal Hospital, Endocrinology & Nutrition, Madrid, Spain; ²Hospital Universitario de Toledo, Endocrinology & Nutrition, Toledo, Spain; ³Hospital Universitario de Coruña, Coruña, Spain; ⁴Hospital Universitario Central de Asturias, Asturias, Spain; ⁵Hospital Universitario Virgen del Rocío, Sevilla, Spain; ⁶Hospital Gregorio Marañón, Madrid, Spain; ⁷Hospital Santiago de Compostela, Spain; ⁸Hospital Universitari de Bellvitge., Spain; ⁹Hospital Universitario de Castellón, Spain; ¹⁰Hospital Clinic de Barcelona, Spain; ¹¹Hospital Ribera, Spain; ¹²Hospital Virgen de las Nieves, Spain; ¹³Hospital Universitario La Fe, Spain; ¹⁴Hospital Universitario San Cecilio., Spain; ¹⁵Hospital Universitario la Princesa, Spain; ¹⁶Hospital Universitario Vall d’Hebrón, Spain; ¹⁷Hospital Germans Trias i Pujol, Spain

Aim: To evaluate the efficacy of second-line therapies in patients with acromegaly caused by a GH and PRL cosecreting pituitary neuroendocrine tumor (GH&PRL-Pit-NET) and those caused by a GH-Pit-NET.

Methods: A multicenter retrospective clinical practice study of 679 patients with acromegaly in follow-up in 33 tertiary hospitals (ACRO-SPAIN study). For this analysis, only patients on treatment with pasireotide or pegvisomant in monotherapy or in combination with other drugs were included (n=150; 22.1%). Patients were classified in two groups: GH-Pit-NET if PRL levels were normal (n=122) and GH&PRL-Pit-NET when evidence of hyperprolactinemia and immunohistochemistry (IHC) for GH and PRL was positive or if PRL levels were >100ng/dl regardless of the PRL IHC (n=28).

Results: A total of 150 patients with acromegaly accomplish the inclusion criteria. A total of 124 patients were treated with pegvisomant and 49 with pasireotide at any time (Table 1). The median time of treatment was of 30.8 months (IQR=15.9-58.2) with pasireotide and 100 months (IQR=34.4-138.5) with pegvisomant. No differences in IGF1 control with pasireotide neither with pegvisomant were observed between GH&PRL-Pit-NETs and GH-Pit-NETs (Table 1). All GH&PRL-Pit-NET cases treated with pasireotide (n=6) and 82.6% (n=19/23) of the cases treated with pegvisomant normalized PRL levels. No differences in the rate of IGF1 control between pegvisomant (in monotherapy or combined with dopamine agonists) vs pasireotide (in monotherapy or combined with dopamine agonists) were detected in patients with GH&PRL-Pit-NET (84.9% vs 66.7%, P=0.178). Neither in the rate of PRL control (80% vs 100%, P=0.234).

Table 1. Differences in the acromegaly presentation and in the response to second-line medical therapies between GH-Pit-NETs and GH&PRL-Pit-NETs
	GH-Pit-NET (n=122)	GH&PRL-Pit-NET (n=28)	P value
CLINICO-RADIOLOGICAL DATA AT ACROMEGALy DIAGNOSIS
Age (years)	46.2±16.03	38.0±13.77	0.017
Knosp>2 (n=118)	51.7% (n=47/91)	74.1% (n=20/27)	0.039
EFFICACy OF SECOND-LINE MEDICAL THERAPIES (IGF normalization)
Pasireotide monotherapy or combined with DA (n=43)	66.7% (n=24/36)	71.4% (n=5/7)	0.806
Pasireotide monotherapy (n=24)	69.6% (n=16/23)	100% (n=1)	0.512
Pasireotide+DA	61.5% (n=8/13)	66.7% (n=4/6)	0.829
Pegvisomant monotherapy or combined with DA/f-SRL (n=118)	84.4% (n=81/96)	77.3% (n=17/22)	0.423
Pegvisomant monotherapy (n=45)	85.7% (n=30/35)	80% (n=8/10)	0.660
Pegvisomant+f-SRL (n=43)	79.5% (n=31/39)	100% (n=4)	0.315
Pegvisomant+DA (n=20)	86.7% (n=13/15)	60% (n=3/5)	0.197
Pegvisomant+pasireotide (n=6)	40% (n=2/5)	100% (n=1)	0.273
DA=dopamine agonists; f-SRL= first generation somatostatin receptor ligands

Conclusion: GH&PRL-Pit-NETs are invasive tumors and present at a younger age than GH-Pit-NETs. However, no differences in the rate of IGF-1 biochemical control with second line therapies were observed between both groups.