Personalized Medicine in Acromegaly: The ACROFAST Study

Abstract

Acromegaly; Personalized therapy; Therapeutic response prediction

Acromegalia; Terapia personalizada; Predicción de la respuesta terapéutica

Acromegàlia; Teràpia personalitzada; Predicció de la resposta terapèutica

Context: Medical treatment of acromegaly is currently performed through a trial-and-error approach using first-generation somatostatin receptor ligands (fgSRLs) as first-line drugs, with an effectiveness of about 50%, and subsequent drugs are indicated through clinical judgment. Some biomarkers can predict fgSRLs response. Objective: Here we report the results of the ACROFAST study, a clinical trial in which a protocol based on predictive biomarkers of fgSRLs was evaluated. Methods: This was a prospective trial (21 university hospitals) comparing the effectiveness and time-to-control of 2 treatment protocols during 12 months: (A) a personalized protocol in which the first options were fgSRLs as monotherapy or in combination with pegvisomant, or pegvisomant as monotherapy depending on the short acute octreotide test (sAOT) results, tumor T2 magnetic resonance (MRI) signal or immunostaining for E-cadherin; and (B) a control group with treatment always started by fgSRLs and the other drugs included after demonstrating inadequate control. Results: Eighty-five patients participated; 45 in the personalized and 40 in the control group. More patients in the personalized protocol achieved hormonal control compared to those in the control group (78% vs 53%, P < .05). Survival analysis revealed a hazard ratio for achieving hormonal control adjusted by age and sex of 2.53 (CI, 1.30-4.80). Patients from the personalized arm were controlled in a shorter period of time (P = .01). Conclusion: Personalized medicine is feasible using a relatively simple protocol, and it allows a higher number of patients to achieve control in a shorter period of time.

This research was funded by the Instituto de Salud Carlos III grant PMP15/00027, co-funded by the European Regional Development Fund - European Union; and PMP22/00021, funded by the European Union-NextGenerationEU, both to Manel Puig-Domingo, and partially supported by the Spanish Society of Endocrinology and Nutrition.