Degarelix for Treating Advanced Hormone-Dependent Prostate Cancer: An Evidence Review Group Perspective of a NICE Single Technology Appraisal

Abstract

As part of its Single Technology Appraisal Process, the National Institute for Health and Care Excellence (NICE) invited the manufacturer of degarelix (Ferring Pharmaceuticals) to submit evidence for the clinical and costeffectiveness of degarelix for the treatment of advanced hormone-dependent prostate cancer. The School of Health and Related Research Technology Appraisal Group at the University of Sheffield was commissioned to act as the independent Evidence Review Group (ERG). The ERG produced a critical review of the evidence contained within the company's submission to NICE. The evidence, which included a randomised controlled trial (RCT) of degarelix versus leuprorelin, found that degarelix was non-inferior to leuprorelin for reduction of testosterone levels and that degarelix achieved a more rapid suppression of prostate-specific antigen levels and subsequently decreased incidences of testosterone flare associated with LHRH agonists. However, protection against testosterone flare for the comparators in the clinical trials was not employed in line with UK clinical practice.Further claims surrounding overall survival, cardiovascular adverse events and clinical equivalence of the comparator drugs from six RCTs of degarelix should be regarded with caution due to flaws and inconsistencies in the pooling of trial data to draw conclusions. The cost-effectiveness evidence included a de novo economic model. Based on the ERG's preferred base case, the deterministic ICER for degarelix versus 3-monthly triptorelin was £14,798 per QALY gained. Additional scenario analyses undertaken by the ERG resulted in ICERs for degarelix versus 3-monthly triptorelin ranging from £17,067 to £35,589 per QALY gained. Subgroup analyses undertaken using the Appraisal Committee's preferred assumptions suggested that degarelix was not costeffective for the subgroup with metastatic disease but could be cost-effective for the subgroup with spinal metastases. The company submitted further evidence to NICE following an initial negative Appraisal Committee decision. Further analyses from the Decision Support Unit found that that whilst there was some evidence that degarelix could be cost-effective for a small subgroup of people with spinal cord compression (SCC), there were insufficient data on the potential size of this subgroup and the rate of SCC in order to estimate an ICER based on the evidence submitted by the company and a separately commissioned systematic review. NICE recommended degarelix as an option for treating advanced hormone-dependent prostate cancer in people with spinal metastases, only if the commissioner can achieve at least the same discounted drug cost as that available to the NHS in June 2016. Key points for decision makers Degarelix is non-inferior to leuprorelin in reducing testosterone to castrate level in those with all stages of prostate cancer requiring androgen deprivation therapy.  Based on the assumptions used in the Evidence Review Group's (ERG) exploratory analyses, the incremental cost effective...

Retrospektive GKV-Versorgungsforschungsstudie über GnRH-Antagonisten/-Agonisten zur initialen Therapie des fortgeschrittenen Prostatakarzinoms – Verordnungsmuster und Krankenhauskosten in Deutschland

“…Diese Tendenz spiegelt sich auch in einer anderen direkten Vergleichsstudie mit 284 Patienten wider: Die 9-Monats-Überlebensrate war für Triptorelin signifikant höher als für Leuprorelin (97,0 % vs. 90,5 %; p = 0,033) [29]. Auch eine Netzwerkanalyse von Uttley et al zeigte eine niedrigere Mortalität unter Triptorelin im Vergleich zu Degarelix [30].…”

Prevalencia de Eventos Cardiocerebrovasculares en Pacientes con Cáncer de Próstata en Manejo con Bloqueo Androgénico con Análogo de GNRH

“…14 Incluso se discute la metodología empleada en varios de los trabajos que establecen la asociación. 5 Entre ellos, un metanálisis publicado en JAMA, no logró demostrar la asociación entre el uso de los agonistas de la GnRh y la mortalidad cardiovascular. 12 Esos hallazgos hacen que la evidencia sea contradictoria.…”

“…4 De igual manera, se encuentra evidencia contradictoria entre el uso de agonistas de la GnRh específicamente y el aumento de eventos cardiovasculares. 5 Todo ello ha conducido a que diversas sociedades científicas elaboren recomendaciones sobre la necesidad de valorar el incremento del riesgo que se produce en esas circunstancias. 6 El objetivo principal de este estudio es determinar la prevalencia de eventos cardiocerebrovasculares en pacientes con cáncer de próstata que son tratados con bloqueo androgénico con agonistas de la GNRH.…”

An Update on Triptorelin: Current Thinking on Androgen Deprivation Therapy for Prostate Cancer

“…A technology appraisal commissioned by the National Institute for Health Care and Excellence (NICE) in the UK reviewed the evidence supporting the use of the GnRH antagonist degarelix for the treatment of advanced prostate cancer and selected leuprolide, goserelin, and triptorelin as comparators [ 61 ]. A mixed treatment comparison meta-analysis of a total of six studies of the selected agents revealed that leuprolide and goserelin were associated with increased mortality compared with degarelix (odds ratio [OR] 1.8 and 1.9, respectively).…”

“…A mixed treatment comparison meta-analysis of a total of six studies of the selected agents revealed that leuprolide and goserelin were associated with increased mortality compared with degarelix (odds ratio [OR] 1.8 and 1.9, respectively). In contrast, mortality with triptorelin was lower than with degarelix (OR 0.5), leading the NICE Evidence Review Group to consider that the treatment effect of triptorelin on overall survival may differ from that of leuprolide and goserelin [ 61 ]. While this analysis is intriguing, more large-scale head-to-head comparisons would be needed to draw firm conclusions on the effects of different ADTs on survival.…”