Clinical Safety and Oncologic Outcomes with GnRH Antagonists and Agonists in Metastatic Prostate Cancer
Introduction
Androgen deprivation therapy is the mainstay for metastatic prostate cancer (PCa). Several studies have shown that gonadotrophin-releasing hormone (GnRH) antagonists and agonists are well tolerated by patients. However, there is lack of clarity on the benefits, adverse effects (AEs) and cardiovascular disease associated with both the drugs. The data on the oncologic outcomes with GnRH antagonists and agonists is also scarce.
Aim
The clinical safety and oncologic outcomes with GnRH antagonists and agonists have been further assessed in patients with metastatic PCa.
Method
Study Design
- Systematic review and meta-analysis
Treatment Strategy
- Randomized controlled trials comparing the clinical safety and oncologic outcomes of GnRH agonists and antagonists were identified after an extensive literature search using MEDLINE, Web of Science, Cochrane Library, and Scopus databases
- Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines were used to conduct the meta-analysis
Endpoints
- Clinical Safety Outcomes:
- Treatment-related adverse effects (TEAEs)
- Serious adverse effects (SAEs)
- Drop-out rates
- Adverse effects:
- Cardiovascular events
- Musculoskeletal events
- Injection site reactions
- Fatigue
- Oncologic outcomes:
- Overall mortality
- PSA progression
Summarized as relative risk (RR) with 95% confidence intervals (95% CI).
Results
- A total of 8 clinical trials comprising 2632 men were included for meta-analysis
- GnRH antagonist and GnRH agonist were received by 1646 and 986 men respectively
- Safety outcomes were evaluated in 7 studies
- Comparison of safety outcomes have been shown in table 1.
| Outcomes | GnRH antagonists (proportion in %) | GnRH agonists (proportion in %) | RR (95% CI) | p value |
| Clinical Safety Outcomes | ||||
| TEAEs | 73% | 68% | 1.1 (1.04 – 1.15) | 0.0003 |
| Serious AEs | 9.8% | 11% | 0.92 (0.73 – 1.17) | 0.49 |
| Drop-out rates | 6.5% | 5.9% | 1.12 (0.81 – 1.54) | 0.49 |
| Adverse Effects | ||||
| Cardiovascular events | - | - | 0.52 (0.34 – 0.80) | 0.003 |
| Musculoskeletal events | - | - | 0.76 (0.60 – 0.95) | 0.02 |
| Injection site reaction rate | 38% | 4.8% | 8.73 (6.48 – 11.78) | <0.0001 |
| Fatigue | - | - | 0.91 (0.69 – 1.21) | 0.52 |
| Oncologic Outcomes | ||||
| Overall mortality | - | - | 0.48 (0.26 – 0.90) | 0.02 |
| PSA progression | - | - | 1.02 (0.69 – 1.50) | 0.92 |
- Antagonists were associated with lower musculoskeletal and cardiovascular events (RR: 0.76 and 0.52, respectively)
- The difference in PSA progression between antagonists and agonists was insignificant (RR: 1.02; p=0.92)
- The overall mortality rate was lower in GnRH antagonist group (RR: 0.48, 95% CI: 0.26–0.90, p = 0.02).
Conclusion
Physicians prescribing ADT should bear in mind and counsel their prospective patients for ADT on the following benefits, risks and lack of them before prescription:
- The GnRH antagonists were associated with lower risk of overall mortality, cardiovascular and musculoskeletal events as compared to agonists, according to the data based from trials with a short-term duration
- The incidence of adverse events and injection site reaction rates were lower with GnRH agonists
- The PSA progression, serious adverse events and drop-out rates were similar with both these forms of androgen deprivation therapy.
Eur Urol. 2020. Doi: 10.1016/j.eururo.2020.06.002.
