LCD L39387: Luteinizing Hormone-Releasing Hormone (LHRH) Analogs

Luteinizing Hormone-Releasing Hormone (LHRH) Analogs are synthetic analogs of the naturally occurring gonadotropin releasing hormone (GnRH) with greater potency than the naturally occurring hormone, that when given inhibits pituitary gonadotropin secretion and suppresses testicular and ovarian steroidogenesis.

Leuprolide acetate (Lupron Depot ® ) , goserelin acetate (Zoladex ® ) , triptorelin pamoate (Trelstar ® ) , histrelin acetate (Vantas ® ) are synthetic LHRH agonists, analogs of the naturally occurring GnRH, and leuprolide mesylate (Camcevi ® ) . They will be covered for Food and Drug Administration (FDA) approved indications. The dose and frequency of administration should be consistent with the FDA approved labeling.

Covered Indications

Leuprolide Acetate is covered for endometriosis, uterine fibroids, advanced prostate cancer, head and neck cancer (salivary gland tumors), ovarian cancer/fallopian tube cancer/primary peritoneal cancer, premenopausal breast cancer, male breast cancer, central precocious puberty (CPP) and palliative treatment of advanced prostate cancer. 1 Leuprolide mesylate is covered for advanced prostate cancer. 12 The National Comprehensive Cancer Network ® (NCCN) Clinical Practice Guidelines in Oncology for Breast Cancer ® 14 , the NCCN Clinical Practice Guidelines in Oncology for Head and Neck Cancers ® 15 , the NCCN Clinical Practice Guidelines in Oncology for Ovarian Cancer ®16 , and the NCCN Clinical Practice Guidelines in Oncology for Prostate Cancer ®17 are referenced for recommendations for coverage across each of these disease settings.

Goserelin implant is covered for locally confined prostate cancer in combination with flutamide; for stage T2b-T4 (stage B2-C) flutamide is recommended only with radiation in this disease setting. Goserelin implant is covered for advanced breast cancer in premenopausal and perimenopausal women, endometriosis, to thin the endometrial lining of the uterus prior to endometrial ablation for dysfunctional uterine bleeding, and palliative treatment of advanced prostate cancer. 2 The NCCN Clinical Practice Guidelines in Oncology for Breast Cancer ® is cited to nationally recognized guidelines to accommodate specific clinical scenarios. 14 The NCCN Clinical Practice Guidelines in Oncology for Prostate Cancer ® is cited to nationally recognized guidelines to accommodate specific clinical scenarios for “advanced prostate cancer.” 17

Triptorelin pamoate is covered for palliative treatment of advanced prostate cancer. 3 The NCCN Clinical Practice Guidelines in Oncology for Prostate Cancer ® is cited to nationally recognized guidelines to accommodate specific clinical scenarios for “advanced prostate cancer.” 17

Histrelin acetate implant is covered for CPP.

Note : The NCCN Clinical Practice Guidelines in Oncology for Prostate Cancer ® is cited to nationally recognized guidelines to accommodate specific clinical scenarios for “advanced prostate cancer.” 17

Limitations

Services that are not reasonable and necessary cannot be covered by Medicare in the following:

• The dose and frequency of administration is not consistent with the FDA approved labeling. Doses and frequencies that exceed the FDA recommended dosage/frequency as per the prescribing information, are considered not reasonable and necessary and not covered by Medicare.

• It is contraindicated to administer these products if you have experienced any type of allergic reaction to these drugs or to any of its ingredients.

Lawrence, et al. (2020) conducted a systemic review to create the American Urological Association/American Society for Therapeutic Radiology and Oncology/Society of Urologic Oncology (AUA/ASTRO/SUO) Guideline to aid clinicians in the management of patients with advanced prostate cancer. Clinicians should offer ADT (androgen deprivation therapy) with either LHRH agonists or antagonists or surgical castration in patients with metastatic hormone sensitive prostate cancer (mHSPC) (strong recommendation; evidence level: grade B). The use of primary ADT for the management of mHSPC has been the standard of care (SOC) since its discovery by Huggins and colleagues in the 1940s. 5

Conn, et al. (1991) review article reports the use of GnRH agonist analogues therapy to induce biochemical castration. The suppression of the normal pituitary-gonadal function is sought because physiologic levels of secretion of gonadal steroids which exacerbate an underlying medical condition, such as endometriosis, uterine fibroids, or prostate cancer. 6

Guzick, et al. (2011) conducted a prospective, randomized, double-blind controlled trial to compare the efficacy of leuprolide and continuous oral contraceptives in the treatment of endometriosis associated pain. The major findings of this trial is that both treatment arms provided a significant reduction in pain from baseline and there was no significant difference in the extent of pain relief between the 2 treatment regimens. The strengths of this clinical trial include its study design (randomized, double-blind prospective, multicenter) and the choice of contemporary medical regimens currently in widespread clinical use in the United States. The greatest weakness of the study is its limited sample size, a direct result of significant challenges in subject recruitment. 7

Kendzierski, et al. (2018) assessed the efficacy of leuprolide depot in combination with an aromatase inhibitor delivered monthly compared to once every 3 months in premenopausal women with estrogen receptor (ER)-positive breast cancer in a single center retrospective study. The Suppression of Ovarian Function Trial (SOFT)/Tamoxifen and Exemestane Trial (TEXT) trials solidified GnRH agonists as a definitive option in adjuvant therapy for premenopausal women with ER-positive breast cancer. They concluded leuprolide acetate depot administered every 3 months is as efficacious and tolerable as a monthly injection in combination with an aromatase inhibitor for premenopausal patients with hormone receptor-positive breast cancer. The study’s retrospective design comes with inherent limitations. The patient population was small, and they describe a single institution experience not a larger randomized, multicenter trial of adjuvant hormone therapy in breast cancer patients. 9