Faster Hormonal Control With Personalized Acromegaly Treatment Approach

A personalized treatment protocol was more effective for management of acromegaly — also known as gigantism — than the usual trial-and-error approach, the prospective ACROFAST trial indicated.

When an individualized approach was crafted based on predictive biomarker testing, 78% of patients with acromegaly achieved hormonal control compared with 53% of traditionally-treated patients after a year (P=0.04), reported Joan Gil, PhD, of the Germans Trias i Pujol Research Institute in Badalona, Spain, and colleagues.

Patients were over two times more likely to achieve hormonal control with the personalized approach after adjustment for age and sex (HR 2.53, 95% CI 1.30-4.80), they reported in the Journal of Clinical Endocrinology & Metabolism. Hormonal control was defined as normalized insulin like growth factor 1 (IGF1) standard deviation scores.

“Our aim was to assist the physician in selecting the appropriate acromegaly course of care for each individual patient,” Gil told MedPage Today. “Acromegaly is a rare condition caused by tumors with varying histologies, hence the response to treatment varies greatly.”

Gil explained that its not uncommon for patients with acromegaly to be diagnosed years after active disease and said “it is critical to regulate hormone levels as soon as possible to stop the disease’s progression and all of its comorbidities.”

Despite a less than half effectiveness rate, acromegaly treatment typically starts with first-generation somatostatin receptor ligands (fgSRLs) as first-line drugs (octreotide or lanreotide), followed by other drugs if there’s an inadequate response determined by clinical judgment.

“In order to discontinue this treatment using the trial-and-error method — current clinical practice — the patient must undergo a futile treatment for 6 to 9 months after likely a delay of many years in diagnosis,” said Gil. By taking this more personalized approach, it can help in discarding octreotide/lanreotide in individuals who won’t respond to this medication.

Gil added that as more acromegaly treatments emerge in the coming years, the trial-and-error method will “no longer be viable.”

ACROFAST‘s personalized approach used three tests to predict fgSRLs response: the short Acute Octreotide Test (sAOT) results, tumor T2 MRI signal, and immunostaining for E-cadherin. Then this group of patients was either started on fgSRLs as monotherapy (n=21), pegvisomant as monotherapy (n=6), or a combination of both (n=5).

This method also was favored at the 6-month mark (69% controlled vs 47%, P=0.07), and patients achieved faster hormonal control with the personalized approached (320 days vs 365 days, P=0.010).

“We want the clinicians to be aware of how simple it is to apply individualized treatment in acromegaly,” said Gil. “Doctors might more quickly and efficiently manage an acromegaly patient with just an easy test that takes 2 hours to complete, and includes two hormone measurements and an E-cadherin IHC, which is available in every pathology department.”

The trial was conducted across 21 tertiary referral centers in Spain with 85 patients (45 in the personalized group; 40 controls). Patients were recently diagnosed, were naïve to medical treatment, and hadn’t been cured 3 months after surgical treatment.

The average age was 54, BMI was 29, and largest tumor diameter was around 17 mm. IGF1 standard deviation scores were 6.1 at baseline in the personalized group and 5.3 in the standard treatment group.

Medical treatment for acromegaly during the last 3 months, previous radiotherapy, pregnancy, renal failure (eGFR less than 30 mL/min/1.73 m²), and severe liver disease including encephalopathy, ascites, coagulopathy or hypoalbuminemia were the exclusion criteria.

As for medical treatment given in the trial, octreotide long-acting release (LAR) 20 mg was administered every 4 weeks or lanreotide 90 mg every 4 weeks. Maximal allowed doses were octreotide LAR 30 mg/monthly and lanreotide 120 mg/monthly in case of inadequate control. Pegvisomant was started at a dose of 0.5 mg/kg/week dose.

In the personalized group, patients who didn’t achieve hormonal control tended to be younger, have a higher BMI, and have higher IGF1, as well as tumor diameter and volume. As for the standard treatment group, non-controlled patients tended to have a higher baseline growth hormone level, as well as higher tumor diameter and volume.

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