How to Position Pasireotide LAR Treatment in Acromegaly

Eva C. Coopmans; Ammar Muhammad; Aart J. van der Lely; Joseph A. M. J. L. Janssen; Sebastian J. C. M. M. Neggers

Disclosures

J Clin Endocrinol Metab. 2019;104(6):1978-1988. 

In This Article

Secondary Efficacy Endpoints

Tumor Volume Reduction

Results from a phase II study of 61 patients with active acromegaly showed after 3 months of treatment that short-acting pasireotide resulted in clinically significant (>20%) tumor volume reduction in 39% of patients, which increased to 54%after 6 months of treatment.[18] However, in the C2305 study pasireotide LAR and octreotide LAR therapy were equally effective in reducing tumor volume.[20] In the C2404, tumor volume reduction occurred more often in patients using pasireotide LAR 40 mg (19%) and 60 mg (11%) than in patients whose disease was inadequately controlled on first-generation SRLs (2%).[21] This finding is not entirely surprising because it is plausible that patients whose disease was inadequately controlled with first-generation SRL are more likely to respond to pasireotide LAR treatment than medically naive patients. The mean decrease in tumor volume during the extension study after crossover was 25% for pasireotide LAR and 18% for octreotide LAR, and 54% of patients on pasireotide LAR therapy and 42% of patients on octreotide LAR achieved significant tumor volume reduction.[24] Taken together, these clinical studies suggest that pasireotide LAR might exert a greater effect on tumor control, especially in patients who show no tumor shrinkage after first-generation SRL treatment. In addition, patients with large tumors due to genetic causes such as aryl hydrocarbon receptor–interacting protein mutations and X-linked acrogigantism are often resistant to first-generation SRLs, and therefore this group might be more responsive to pasireotide LAR treatment.[26–28]

Quality of Life and Symptoms

In medically naive patients, pasireotide LAR and octreotide LAR showed similar improvements in acromegaly symptom scores.[20] In the C2404, patients in the pasireotide LAR treatment groups showed more improvement in acromegaly symptom scores than patients whose disease was inadequately controlled on optimal dosages of first-generation SRLs therapy.[21] As mentioned earlier, the observed improvement in acromegaly symptoms in the pasireotide LAR treatment groups was to be expected.

In the PAPE study we observed a significant improvement in the global Acromegaly Quality of Life questionnaire score during treatment with pasireotide LAR, and the greatest improvement was observed in the physical dimension.[29] A subset of patients reported an improvement in quality of life, which was associated mainly with improvement in symptoms of fatigue and headache.[29] Moreover, some analgesic effects of pasireotide have been reported for individual patients.[30,31]

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