PMID-29718793 – GnRH Agonists for Ovarian Protection During Breast Cancer Chemotherapy
Lambertini M et al. "Gonadotropin-Releasing Hormone Agonists During Chemotherapy for Preservation of Ovarian Function and Fertility in Premenopausal Patients With Early Breast Cancer: A Systematic Review and Meta-Analysis of Individual Patient-Level Data," Journal of Clinical Oncology, 2018;36(19):1981-1990. doi:10.1200/JCO.2018.78.0858
Quick Reference
| Property | Value |
|---|---|
| PMID | 29718793 |
| DOI | 10.1200/JCO.2018.78.0858 |
| Year | 2018 |
| Journal | Journal of Clinical Oncology |
| Study Type | Individual Patient Data (IPD) Meta-analysis |
| Evidence Level | I |
| Sample | 873 premenopausal patients across 5 RCTs |
| Peptide(s) Studied | GnRH agonists (Gonadorelin class — triptorelin, goserelin) |
Key Findings
- GnRH agonist co-administration during chemotherapy significantly reduced premature ovarian insufficiency (POI): 14.1% vs. 30.9% (p<0.001)
- Absolute risk reduction of 16.8% for POI — number needed to treat (NNT) = 6
- Post-treatment pregnancy rates were higher in the GnRH agonist group
- No compromise of chemotherapy efficacy — disease-free survival and overall survival were equivalent between groups
- Benefit was consistent across breast cancer subtypes (ER-positive and ER-negative)
- GnRH agonists provide a non-invasive fertility preservation option that can be initiated immediately before chemotherapy
Study Design
Individual patient data (IPD) meta-analysis of 5 randomized controlled trials. 873 premenopausal patients with early breast cancer randomized to chemotherapy with or without concurrent GnRH agonist. Primary endpoint: premature ovarian insufficiency at 2 years post-chemotherapy. Secondary endpoints: pregnancy, disease-free survival, overall survival. IPD analysis allowed consistent endpoint definitions and subgroup analyses.
Limitations
- Heterogeneous chemotherapy regimens across trials
- Definition of premature ovarian insufficiency varied slightly between studies (harmonized in IPD analysis)
- Median follow-up may be insufficient for late ovarian recovery assessment
- Limited to breast cancer; generalizability to other cancers uncertain
- GnRH agonist specific agents differed (triptorelin in some, goserelin in others)
Clinical Relevance
This IPD meta-analysis provides Level I evidence that GnRH agonists preserve ovarian function during breast cancer chemotherapy without compromising oncologic outcomes. Directly relevant for the peptide vault's coverage of GnRH-related peptides and reproductive health. The NNT of 6 is clinically compelling. This supports inclusion of GnRH agonist protocols in the Fertility and Sexual Health module. While the specific agents studied (triptorelin, goserelin) are pharmaceutical GnRH agonists rather than research peptides, the mechanism is identical to Gonadorelin-based protocols.
Related
#research #meta-analysis #evidence-level-I #cancer