Download Medical Policy Trelstar Depot, LA® (triptorelin pamoate)

Medical Policy
Trelstar Depot, LA®
(triptorelin pamoate)
Effective Date: October 1, 2016
Subject: Trelstar Depot, LA® (triptorelin pamoate)
Overview: Trelstar Depot, LA is an injectable Gonadotropin-Releasing Hormone Analog (GnRH) used to treat certain cancers, endocrine disorders, and uterine conditions.
Policy and Coverage Criteria:
NOTE: Prior Authorization is not required
Harvard Pilgrim considers Trelstar Depot, LA (triptorelin pamoate) medically necessary as a
treatment for any of the following:
• Advanced prostate cancer
• Central Precocious Puberty
• Uterine Leiomyomata
Harvard Pilgrim does not cover Trelstar Depot, LA (triptorelin pamoate) for indications not
listed above.
Exclusions: N/A
Supporting Information:
1. Technology Assessment: Triptorelin pamoate is a synthetic decapeptide agonist analog of
luteinizing hormone releasing hormone (LHRH). Triptorelin possesses greater potency than
endogenous LHRH and reversibly represses gonadotropin secretion after prolonged
administration. A sustained decrease in LH, FSH, and testicular and ovarian steroidogenesis
is observed after chronic, continuous administration.
2. Literature Review:
Advanced prostate cancer: Prostate cancer is the most common form of cancer, other
than skin cancer, among men. Wilt et al (2008) report that approximately 90% of men with
prostate cancer have disease confined to the prostate gland. GnRH analogs are commonly
used in the treatment of prostate cancer under specific conditions.
Lebret et al (2015) conducted an open-label, single-arm study to assess the efficacy and
safety profile of triptorelin pamoate when administered subcutaneously. A total of 126
androgen deprivation therapy-naïve men with locally advanced or metastatic prostate cancer
received triptorelin pamoate 11.25 mg subcutaneously at baseline and at 13 weeks. A total of
97.6% were castrated 4 weeks after the first subQ injection, and 96.6% of these patients
castrated at 4 weeks maintained castration at 26 weeks. Median prostate-specific antigen
levels were reduced by 64.2% at 4 weeks and 96% at 26 weeks. The authors concluded that
triptorelin pamoate 11.25 mg administered by the subcutaneous route every 3 months is as
efficacious and well tolerated as administration via the intramuscular route in men with locally
advanced or metastatic prostate cancer.
Kao et al (2012) evaluated the efficacy and safety of administering a 3-month formulation of
triptorelin as part of disease management of 40 Taiwanese men with advanced
adenocarcinoma of the prostate. Patients received bicalutamide 50 mg daily for 28 days,
starting 7 days before the first injection of triptorelin. Triptorelin 11.25 mg was injected at
baseline and repeated on day 90. On day 90, 97.5% of men had reached castration
testosterone concentration ≤0.5 ng/mL and all men had reached this concentration on day
180. Serum PSA concentration declined to 10.40 ± 23.42 ng/mL on day 90 and 11.61 ± 23.93
ng/mL on day 180. The authors concluded that triptorelin 11.25 mg is effective in achieving
medical castration and lowering PSA concentrations and can maintain its medicinal effect for at
least 90 days in Taiwanese men with advanced prostate cancer.
Central Precocious Puberty: Central precocious puberty (CPP) refers to premature
activation of the hypothalamic-pituitary-gonadal axis. The European Society for Pediatric
Endocrinology (2009) indicated that precocious puberty is the development of secondary
sexual characteristics before 8 years of age in girls and 9 years of age in boys. Treatment may
be initiated following the establishment of a clinical diagnosis of CPP; however, the condition
may not be detected or evaluated at onset and treatment can sometimes be started after age
8 or 9. Discontinuation of therapy is a clinical decision and there is insufficient evidence to rely
on any one clinical variable to make that decision.
Carel et al (2006) conducted an open-label, 12 month trial to evaluate the use of triptorelin
11.25 mg 3-month depot in children with central precocious puberty. A total of 64 children (54
girls and 10 boys) were treated quarterly for 12 months. Children with a clinical onset of
pubertal development before the age of 8 years (girls) or 9 years (boys), pubertal response of
LH to GnRH>or = 7 IU/l, advanced bone age>1 year, enlarged uterus (>or = 36 mm) and
testosterone level>or = 0.5 ng/ml (boys), were included. Suppression of gonadotropic
activation, as determined from serum LH, FSH, estradiol or testosterone, and pubertal signs
were assessed at Months 3, 6 and 12. GnRH-stimulated peak LH<or = 3 IU/l was met in 85%,
97% and 95% of the children at Months 3, 6 and 12. Serum FSH and sex steroids were also
significantly reduced, while pubertal development regressed in most patients. Mean residual
triptorelin levels were stable from month 3 through to month 12. The triptorelin 3-month
depot was well tolerated. The authors concluded that the triptorelin 3-month depot efficiently
suppresses the pituitary-gonadal axis and pubertal development in children with CPP.
Uterine Leiomyomata: Preoperative use of GnRH agonists provides some short-term
benefits for women undergoing myomectomy regarding blood loss and uterine size, but may
increase the difficulty of surgery, however, their use appears to increase the risk of
persistent/recurrent myomas.
Lethaby ey al (2011) conducted a meta-analysis of 11 randomized trials comparing women
planning abdominal myomectomy who were treated with a GnRH agonist for three to four
months with those receiving either placebo or no treatment. Preoperative GnRH agonist
therapy resulted in a small, but statistically significant, increase in preoperative hemoglobin. A
reduction in intraoperative blood loss was another observed benefit.
Muzii et al (2010) conducted a prospective, randomized, clinical study to evaluate the efficacy
of GnRH analogue treatment before hysteroscopic resection of submucous myomas in patients
with abnormal uterine bleeding. A total of 39 patients with submucous myomas graded as G0
or G1 according to the European Society for Gynecological Endoscopy classification were
randomized to either direct surgery or 2 months of GnRH analogues before undergoing
hysteroscopic resection of the submocous myoma. Patients treated with the GnRH analogue
had significantly shorter operative times and reduced fluid absorption compared with no
preoperative medical treatment. Operative difficulty and overall surgeon satisfaction were
significantly better in the GnRH analogue group. The two groups showed similar patient
satisfaction. The authors concluded that GnRH analogue treatment before hysteroscopic
resection of G0-G1 10-35 mm submucous myomas was effective in reducing operative times,
fluid absorption, and difficulty of the procedure.
Codes:
HCPCS
J3315 – injection, triptorelin pamoate, 3.75 mg [Trelstar, Trelstar Depot, Trelstar LA]
Medically necessary ICD-10 Diagnosis Codes
C61 – Malignant neoplasm of prostate
D25.0 – Submucous leiomyoma of uterus
D25.1 – Intramural leiomyoma of uterus
D25.2 – Subserosal leiomyoma of uterus
D25.9 – Leiomyoma of uterus, unspecified
E30.1 – Precocious puberty
E30.8 – Other disorders of puberty
Z85.46 – Personal history of malignant neoplasm of the prostate
References:
1. Facts & Comparison 4.0 Online
2. Trelstar PI
3. NCCN Compendia Online
4. Clinical Pharmacology Online
5. Bergqvist A, Bergh T, Hogström L, et al. Effects of triptorelin versus placebo on the
symptoms of endometriosis. Fertil Steril. 1998 Apr;69(4):702-8.
6. Donnez J, Dewart PJ, Hedon B, et al. Equivalence of the 3-month and 28-day formulations
of triptorelin with regard to achievement and maintenance of medical castration in women
with endometriosis. Fertil Steril. 2004 Feb;81(2):297-304.
7. Carel, JC., Blumberg, J., Seymour, C., et al. Three-month sustained-release triptorelin
(11.25 mg) in the treatment of central precocious puberty. Eur J Endocrinol. 2006;
154(1):119.
8. Lebret, T., Rouanne, M., Hublarov, O., et al. Efficacy of triptorelin pamoate 11.25 mg
administered subcutaneously for achieving medical castration levels of testosterone in
patients with locally advanced or metastatic prostate cancer. Ther Adv Urol. 2015;
7(3):125-134.
9. Kao, CC., Chang, YH., Wu, T., Sun, GH., Yu, DS., Chang, SY., Cha, TL. Open, multi-center,
phase IV study to assess the efficacy and tolerability of triptorelin in Taiwanese patients
with advanced prostate cancer. J Chin Med Assoc. 2012; 75(6):255-61.
10. Wilt TJ, MacDonald R, Rutks I, et al. Systematic review: comparative effectiveness and
harms of treatments for clinically localized prostate cancer. Ann Intern Med. 2008;
148(6):435-448.
11. Carel JC, Eugster EA, Rogol A, et al. Consensus statement on the use of gonadotropinreleasing hormone analogs in children. Pediatrics. 2009; 123(4):e752-762.
12. Eugster EA, Clarke W, Kletter GB, et al. Efficacy and safety of histrelin subdermal implant in
children with central precocious puberty: a multicenter trial. J Clin Endocrinol Metab. 2007;
92(5):1697-1704.
13. Phillip M, Lazar L. Precocious puberty: growth and genetics. Horm Res. 2005; 64 Suppl
2:56-61.
14. Muzii, L., Boni, T., Bellati, F., et al. GnRH analogue treatment before hysteroscopic
resection of submucous myomas: a prospective, randomized, multicenter study. Fertil
Steril. 2010; 94(4):1496-9.
15. Lethaby, A., Vollenhoven, B., Sowter, M. Pre-operative GnRH analogue therapy before
hysterectomy or myomectomy for uterine fibroids. Cochrane Database Syst Rev. 2011.