PMID-25260838 – PAOLA Pasireotide vs Octreotide Lanreotide in Acromegaly
Gadelha MR, Bronstein MD, Brue T, et al. Pasireotide versus continued treatment with octreotide or lanreotide in patients with inadequately controlled acromegaly (PAOLA): a randomised, phase 3 trial. Lancet Diabetes Endocrinol. 2014;2(11):875-884.
Quick Reference
| Property | Value |
|---|---|
| PMID | 25260838 |
| DOI | 10.1016/S2213-8587(14)70169-X |
| Year | 2014 |
| Journal | Lancet Diabetes & Endocrinology |
| Study Type | RCT |
| Evidence Level | I |
| Sample | 198 patients with inadequately controlled acromegaly |
| Peptide(s) Studied | Pasireotide, Octreotide, Lanreotide |
Key Findings
- Biochemical control (GH <2.5 mcg/L + normalized IGF-1) achieved in 15.4% (pasireotide 40 mg) and 20.0% (pasireotide 60 mg) vs 0% (active control) at 24 weeks (p < 0.0001 for both)
- IGF-1 normalization alone achieved in 38.6% (60 mg) vs 1.5% (control)
- Pasireotide LAR demonstrated superiority over first-generation somatostatin analogs in patients who had failed octreotide or lanreotide
- Tumor volume reduction was observed in both pasireotide dose groups
- Hyperglycemia remained the main safety concern: 57% of pasireotide patients had hyperglycemia-related AEs vs 24% in the control group
- Quality of life (AcroQoL) improved more with pasireotide
Study Design
Multicenter, randomized, Phase III, three-arm trial (PAOLA; NCT01137682). Patients with inadequately controlled acromegaly despite >=6 months of octreotide LAR or lanreotide Autogel were randomized 1:1:1 to pasireotide LAR 40 mg IM, pasireotide LAR 60 mg IM, or continued active control (octreotide LAR 30 mg or lanreotide Autogel 120 mg) every 28 days for 24 weeks. Primary endpoint: biochemical control at 24 weeks.
Limitations
- 24-week primary endpoint is relatively short for chronic disease management
- No dose optimization phase for active control (patients stayed on same dose that was already inadequate)
- Higher rate of hyperglycemia with pasireotide requires careful risk-benefit assessment
- Open-label after randomization could introduce assessment bias
Clinical Relevance
The PAOLA trial established pasireotide LAR as a second-line therapy for acromegaly in patients not adequately controlled on first-generation somatostatin analogs. This led to FDA approval of pasireotide LAR (Signifor LAR) for acromegaly in 2014. The broader receptor binding profile (SSTR1,2,3,5) explains the incremental efficacy but also the metabolic side effects (particularly SSTR5-mediated insulin suppression). Clinicians must weigh improved biochemical control against the significant diabetes risk.
Related
#research #RCT #pasireotide #evidence-level-I