PMID-25014687 – CLARINET Lanreotide for Enteropancreatic NETs Phase III
Caplin ME et al. "Lanreotide in metastatic enteropancreatic neuroendocrine tumors," New England Journal of Medicine, 2014;371(3):224-233. doi:10.1056/NEJMoa1316158
Quick Reference
| Property | Value |
|---|---|
| PMID | 25014687 |
| DOI | 10.1056/NEJMoa1316158 |
| Year | 2014 |
| Journal | New England Journal of Medicine |
| Study Type | Phase III Randomized Controlled Trial |
| Evidence Level | I |
| Sample | n=204 patients with metastatic enteropancreatic NETs |
| Peptide(s) Studied | Lanreotide (somatostatin analogue peptide) |
Key Findings
- Phase III double-blind, placebo-controlled RCT demonstrating that lanreotide depot significantly prolongs progression-free survival in metastatic enteropancreatic NETs
- PFS hazard ratio: 0.47 (p<0.001) — a 53% reduction in risk of disease progression or death with lanreotide vs placebo
- Median PFS was not reached in the lanreotide group vs 18.0 months in the placebo group at the time of analysis
- PFS at 24 months: 65.1% (lanreotide) vs 33.0% (placebo)
- Treatment effect was consistent across subgroups: midgut vs pancreatic origin, hepatic tumor burden, and prior therapy status
- Lanreotide was well tolerated; most common adverse events were diarrhea (26%) and abdominal pain (14%), consistent with somatostatin analogue class effects
- This trial expanded the indication for somatostatin analogue peptides beyond symptom control to antiproliferative therapy in NETs
Study Design
International, multicenter, double-blind, placebo-controlled Phase III RCT (CLARINET). Patients with well- or moderately-differentiated, non-functioning, somatostatin receptor-positive metastatic enteropancreatic NETs were randomized 1:1 to lanreotide depot 120mg deep subcutaneous injection every 28 days or placebo. Primary endpoint was PFS by RECIST 1.1 with central radiology review.
Limitations
- Restricted to non-functioning, well/moderately differentiated tumors — excludes poorly differentiated or functioning NETs
- Overall survival data not reported; PFS as surrogate
- No quality-of-life data reported in the primary publication
- Somatostatin receptor expression level was not used as a stratification factor
- The study did not compare lanreotide with octreotide LAR (another somatostatin analogue)
Clinical Relevance
CLARINET established lanreotide as a first-line antiproliferative therapy for metastatic enteropancreatic NETs, complementing the earlier PROMID trial for octreotide. Together, these trials confirm that somatostatin analogue peptides have direct antitumor activity beyond symptom control. For the peptide therapy field, CLARINET demonstrates that a naturally-derived peptide analogue (somatostatin) can serve as an effective cancer treatment. This is one of the few examples of a peptide drug approved for oncological indications based on Phase III RCT evidence.
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#research #RCT #evidence-level-I #cancer