Proven
Efficacy and Safety
Across Multiple Dosing Options

Jackson, age 67
Retired high school basketball coach
Husband, grandfather of 4

LUPRON DEPOT delivers testosterone suppression below castrate levels across multiple formulations, as shown in multicenter clinical trials enrolling patients with histologically confirmed advanced prostate cancer.1

Effective Testosterone Suppression

In an open-label, noncomparative, multicenter study

Testosterone Suppression With 6-Month Dosing

A graph showing testosterone suppression with 6-month dosing A graph showing testosterone suppression with 6-month dosing A graph showing testosterone suppression with 6-month dosing

Primary Endpoint1,2

Serum testosterone was suppressed to ≤50 ng/dL from week 4 through week 48 in 93.4% of patients (two-sided 95% Cl: 89.2%, 97.6%, N=148).

Jackson, a LUPRON DEPOT patient, standing proudly and smiling

Safety With 6-Month Dosing

Adverse Events in ≥ 5% of Patients1 Treatment Emergent n=151 (%) Treatment Related n=151 (%)

Hot Flush/Flushing

89 (58.9)

88 (58.3)

Injection Site Pain/Discomfort

29 (19.2)

16 (10.6)

Upper Respiratory Tract
Infection/Influenza-like Illnessa

32  (21.2)

0 (0)

Fatigue/Lethargy

20 (13.2)

18 (11.9)

Constipation

15 (9.9)

5 (3.3)

Arthralgia

14 (9.3)

2 (1.3)

Insomnia/Sleep Disorder

13 (8.6)

5 (3.3)

Headache/Sinus Headache

12 (7.9)

3 (2.0)

Musculoskeletal Pain/Myalgia

12 (7.9)

3 (2.0)

Second Primary Neoplasmb

11 (7.3)

0 (0)

Cough

10 (6.6)

2 (1.3)

Hematuria/Hemorrhagic Cystitis

10 (6.6)

0 (0)

Hypertension/BP Increased

10 (6.6)

3 (2.0)

Rash

9 (6.0)

3 (2.0)

Dysuria

9 (6.0)

1 (0.7)

Urinary Tract Infection/Cystitis

9 (6.0)

0 (0)

Anemia/Hemoglobin Decreased

10 (6.6)

2 (1.3)

Back Pain

8 (5.3)

0 (0)

COPD

8 (5.3)

0 (0)

Dizziness

8 (5.3)

3 (2.0)

Dyspnea/Dyspnea on Exertion

8 (5.3)

2 (1.3)

Nocturia

8 (5.3)

2 (1.3)

Peripheral/Pitting Edema

8 (5.3)

2 (1.3)

Coronary Artery Disease/Angina

8 (5.3)

1 (0.7)

a Includes influenza, nasal congestion, nasopharyngitis, rhinorrhea, upper respiratory tract infection, and viral upper respiratory tract infection.

b Includes basal cell carcinoma, bladder transitional cell carcinoma, lung neoplasm, malignant melanoma, non-Hodgkin lymphoma, and squamous cell carcinoma.

In an open-label, noncomparative, multicenter study

Testosterone Suppression With 4-Month Dosing

A graph showing testosterone suppression with 4-month dosing A graph showing testosterone suppression with 4-month dosing A graph showing testosterone suppression with 4-month dosing

Primary Endpoint1,4

Castrate levels were achieved in 94% of patients by day 30, and in all patients by day 43. After falling to castrate range, mean testosterone levels remained within the castrate range throughout each dosing interval.

Safety With 4-Month Dosing

The 4-month formulation of LUPRON DEPOT 30 mg was utilized in clinical trials that studied the drug in 49 nonorchiectomized prostate cancer patients for 32 weeks or longer and in 24 orchiectomized prostate cancer patients for 20 weeks.

Adverse Events in ≥ 5% of Patients1 Nonorchiectomized
n=49 (%)
Orchiectomized
n=24 (%)

Body as a Whole

Asthenia

6 (12.2)

1 (4.2)

Flu Syndrome

6 (12.2)

0 (0.0)

General Pain

16 (32.7)

1 (4.2)

Headache

5 (10.2)

1 (4.2)

Injection Site Reaction

4 (8.2)

9 (37.5)

Cardiovascular System

Hot Flashes/Sweats

23 (46.9)

2 (8.3)

Digestive System

GI Disorders

5 (10.2)

3 (12.5)

Metabolic and Nutritional Disorders

Dehydration

4 (8.2)

0 (0)

Edema

4 (8.2)

5 (20.8)

Musculoskeletal System

Joint Disorder

8 (16.3)

1 (4.2)

Myalgia

4 (8.2)

0 (0)

Nervous System

Dizziness/Vertigo

3 (6.1)

2 (8.3)

Neuromuscular Disorders

3 (6.1)

1 (4.2)

Paresthesia

4 (8.2)

1 (4.2)

Respiratory System

Respiratory Disorder

4 (8.2)

1 (4.2)

Skin and Appendages

Skin Reactions

6 (12.2)

0 (0)

Urogenital System

Urinary Disorders

5 (10.2)

4 (16.7)

Post Hoc Analysis of Combined 4- and 6-Month Data

Considerations for Testosterone Measurement

  • Based on assays available 40 years ago, surgical castrate levels of testosterone were reported as <50 ng/dL6,7
  • US FDA and American Urological Association (AUA) currently define medical castration as testosterone levels <50 ng/dL8,9
  • Current testosterone assay techniques are more rapid and accurate6
  • Surgical castrate level using current assays determined as median 15 ng/dL (95% Cl: 12-17 ng/dL)6
  • <20 ng/dL is the recommended goal for ADT therapy by the European Association of Urology Guidelines (EAU) 2019 and Bethesda consensus 20117,10
  • No robust clinical data have clearly established the value of achieving testosterone <20 ng/dL6,10

Post hoc analysis of combined 4- and 6-month data, including pooled data

In a combined post hoc analysis of two phase 3 open-label studies in patients with histologically confirmed prostate adenocarcinoma, serum testosterone levels were pooled at each common timepoint to determine the number and proportion of patients who had levels <20 ng/dL. Assays with similar testosterone sensitivity were used.11

Limitations

Post hoc analyses are not powered or tested to demonstrate statistically significant differences in treatment effect. Pooled data limitation: patients with histologically confirmed adenocarcinoma were evaluated. Cancer staging and other patient characteristics (eg, age, prior treatment) may have been different between studies. The relationship between testosterone values and clinical outcomes has not been established.

PERCENTAGE OF PATIENTS WITH TESTOSTERONE
≤ 20 NG/DL OVER TIME DURING PHASE 3 STUDIES11

% of Patlents With Serum Testosterone ≤ 20 ng/dL
Weeks
n=193 n=191 n=42 n=41 n=194 n=189 n=41 n=34 n=135 78.8 4 96.9 8 97.6 12 90.2 16 94.8 20 89.4 24 100 28 97.1 32 36 40 44 94.1 48
  • Pooled data
  • 4-month data
  • 6-month data
  • In the pooled analysis, mean serum testosterone was suppressed to <20 ng/dL in 79% to 97% of patients from week 4 through week 2411
  • In the 6-month formulation of LUPRON DEPOT, 94.1% of patients were suppressed <20 ng/dL at week 4811
In two nearly identical open-label, noncomparative, multicenter studies

Testosterone Suppression With 3-Month Dosing

A graph showing testosterone suppression with 3-month dosing A graph showing testosterone suppression with 3-month dosing A graph showing testosterone suppression with 3-month dosing

Primary Endpoint Results1,12

Castrate levels (50 ng/dL) of testosterone were achieved within 30 days of the initial injection in 95% (87/92) of patients in the two studies. After falling to castrate range, mean testosterone levels remained within the castrate range throughout each 12-week dosing interval.

Safety With 3-Month Dosing

Adverse Events in ≥ 5% of Patients1 N=94 %

Body as a Whole

Asthenia

7

7.4

General Pain

25

26.6

Headache

6

6.4

Injection Site Reaction

13

13.8

Cardiovascular System

Hot Flashes/Sweats

55

58.5

Digestive System 

GI Disorders

15

16.0

Musculoskeletal System

Joint Disorder

11

11.7

Central/Peripheral Nervous System

Dizziness/Vertigo

6

6.4

Insomnia/Sleep Disorders

8

8.5

Neuromuscular Disorders

9

9.6

Respiratory System

Respiratory Disorders

6

6.4

Skin and Appendages

Skin Reactions

8 8.5

Urogenital System

Testicular Atrophy

19

20.2

Urinary Disorders

14

14.9

Indication1

LUPRON DEPOT® (leuprolide acetate for depot suspension) 7.5 mg for 1‑month, 22.5 mg for 3-month, 30 mg for 4‑month, and 45 mg for 6‑month administration are indicated for the palliative treatment of advanced prostatic cancer.

Important Safety Information1

  • LUPRON DEPOT is contraindicated in patients with hypersensitivity to GnRH agonists or any of the excipients in LUPRON DEPOT.
  • LUPRON DEPOT causes an initial increase in serum testosterone (~50% above baseline) during the first few weeks of treatment. This initial increase can cause:
    • Transient worsening of symptoms, or additional signs and symptoms of prostate cancer.
    • Temporary increase in bone pain in a small number of patients, which can be managed symptomatically.
    • Isolated cases of ureteral obstruction and spinal cord compression, which may contribute to paralysis with or without fatal complications. Observe patients with vertebral metastasis and/or urinary tract obstruction closely.
  • Hyperglycemia and increased risk of developing diabetes have been reported in men receiving GnRH agonists. Monitor blood glucose and/or glycosylated hemoglobin (HbA1c) periodically in men receiving a GnRH agonist, and manage hyperglycemia or diabetes.
  • An increased risk of myocardial infarction, sudden cardiac death, and stroke has been reported in association with the use of GnRH agonists in men, although the risk appears low. Evaluate the risks carefully, including cardiovascular risk factors, when determining prostate cancer treatment. Patients receiving a GnRH agonist should be monitored for signs and symptoms of cardiovascular disease and managed appropriately.
  • Androgen deprivation therapy (ADT) may prolong the QT/QTc interval. Consideration should be given to whether the benefits of ADT outweigh the potential risks in patients with congenital long QT syndrome, congestive heart failure, frequent electrolyte abnormalities, and in patients taking drugs known to prolong the QT interval. Correct electrolyte abnormalities and consider periodic monitoring of electrocardiograms and electrolytes.
  • Postmarketing reports of convulsions have been observed in patients on leuprolide acetate therapy, including patients with a history of seizures, epilepsy, cerebrovascular disorders, central nervous system anomalies or tumors, and in patients on concomitant medications associated with convulsions, such as bupropion and SSRIs. Convulsions have also been reported in the absence of any of the conditions mentioned above.
  • Periodic monitoring of serum testosterone and PSA levels is recommended.
  • LUPRON DEPOT may cause fetal harm when administered to a pregnant woman. Advise pregnant patients and females of reproductive potential of the potential risk to the fetus.
  • LUPRON DEPOT may impair fertility in males of reproductive potential.
  • In controlled clinical trials of advanced prostatic cancer patients receiving LUPRON DEPOT, the following adverse events occurred in >10% of patients:
    • LUPRON DEPOT 7.5 mg for 1‑month administration: hot flashes/sweats, general pain, edema, urinary disorders, GI disorders, and respiratory disorders.
    • LUPRON DEPOT 22.5 mg for 3‑month administration: hot flashes/sweats, general pain, testicular atrophy, GI disorders, urinary disorders, injection site reactions, and joint disorders.
    • LUPRON DEPOT 30 mg for 4‑month administration: hot flashes/sweats, injection site reactions, general pain, edema, urinary disorders, joint disorders, GI disorders, asthenia, flu syndrome, skin reactions, and headache.
    • LUPRON DEPOT 45 mg for 6‑month administration: hot flush/flushing, upper respiratory tract infection/influenza-like illness, injection site pain/discomfort, and fatigue/lethargy.

US-LUPR-190307

Please see accompanying Full Prescribing Information.

References

  1. LUPRON DEPOT [package insert]. North Chicago, IL: AbbVie Inc; 2019.

  2. Spitz A, Young JM, Larsen L, et al. Efficacy and safety of leuprolide acetate 6-month depot for suppression of testosterone in patients with prostate cancer. Prostate Cancer Prostatic Dis. 2012;15(1):93-99. doi:10.1038/pcan.2011.50.

  3. Data on file. AbbVie Inc. ABVRRTI69626.

  4. Sharifi R, Dean Knoll L, Smith J, et al. Leuprolide acetate (30-mg depot every four months) in the treatment of advanced prostate cancer. Urology. 1998;51(2):271-276. doi:10.1016/S0090-4295(97)00500-1.

  5. Data on file. AbbVie Inc. ABVRRTI69625.

  6. Oefelein M, Feng A, Scolieri M, et al. Reassessment of the definition of castrate levels of testosterone: implications for clinical decision making. Urology. 2000;56(6):1021-1024. doi:10.1016/S0090-4295(00)00793-7.

  7. European Association of Urology. Prostate cancer. https://uroweb.org/guideline/prostate-cancer/#6. Accessed October 8, 2019.

  8. US Food & Drug Administration. Advanced Prostate Cancer: Developing Gonadotropin-Releasing Hormone Analogues Guidance for Industry. https://www.fda.gov/media/129027/download. Accessed October 8, 2019.

  9. Cookson MS, Roth BH, Dahm P, et al; American Urological Association. Castration-Resistant Prostate Cancer: AUA Guideline. https://www.auanet.org/guidelines/prostate-cancer-castration-resistant-guideline. Approved May 2018. Accessed October 8, 2019.

  10. Djavan B, Eastham J, Gomella L, et al. Testosterone in prostate cancer: the Bethesda consensus. BJU Int. 2012; 110(3):334-352. doi:10.1111/j.1464-410X.2011.10719.x.

  11. Spitz A, Gittelman M, Karsh LI, et al. Intramuscular depot formulations of leuprolide acetate suppress testosterone levels below a 20 ng/dL threshold: a retrospective analysis of two Phase III studies. Res Rep Urol. 2016;8:159-164. doi:10.2147/RRU.S111475.

  12. Sharifi R, Bruskewitz RC, Gittleman MC, et al. Leuprolide acetate 22.5 mg 12-week depot formulation in the treatment of patients with advanced prostate cancer. Clin Ther. 1996;18(4):647-657. doi:10.1016/S0149-2918(96)80215-3.

  13. Data on file. AbbVie Inc. ABBRRTI69627.

Indication1

LUPRON DEPOT® (leuprolide acetate for depot suspension) 7.5 mg for 1‑month, 22.5 mg for 3-month, 30 mg for 4‑month, and 45 mg for 6‑month administration are indicated for the palliative treatment of advanced prostatic cancer.

Important Safety Information1

LUPRON DEPOT is contraindicated in patients with hypersensitivity to GnRH agonists or any of the excipients in LUPRON DEPOT. LUPRON DEPOT causes an initial increase in serum testosterone (~50% above baseline) during the first few weeks of treatment. This initial increase can cause:

Indication1

LUPRON DEPOT® (leuprolide acetate for depot suspension) 7.5 mg for 1‑month, 22.5 mg for 3-month, 30 mg for 4‑month, and 45 mg for 6‑month administration are indicated for the palliative treatment of advanced prostatic cancer.

Important Safety Information1

LUPRON DEPOT is contraindicated in patients with hypersensitivity to GnRH agonists or any of the excipients in LUPRON DEPOT. LUPRON DEPOT causes an initial increase in serum testosterone (~50% above baseline) during the first few weeks of treatment. This initial increase can cause:

Indication1

LUPRON DEPOT® (leuprolide acetate for depot suspension) 7.5 mg for 1‑month, 22.5 mg for 3-month, 30 mg for 4‑month, and 45 mg for 6‑month administration are indicated for the palliative treatment of advanced prostatic cancer.

Important Safety Information1

LUPRON DEPOT is contraindicated in patients with hypersensitivity to GnRH agonists or any of the excipients in LUPRON DEPOT. LUPRON DEPOT causes an initial increase in serum testosterone (~50% above baseline) during the first few weeks of treatment. This initial increase can cause:

Indication1

LUPRON DEPOT® (leuprolide acetate for depot suspension) 7.5 mg for 1‑month, 22.5 mg for 3-month, 30 mg for 4‑month, and 45 mg for 6‑month administration are indicated for the palliative treatment of advanced prostatic cancer.

Important Safety Information1

LUPRON DEPOT is contraindicated in patients with hypersensitivity to GnRH agonists or any of the excipients in LUPRON DEPOT. LUPRON DEPOT causes an initial increase in serum testosterone (~50% above baseline) during the first few weeks of treatment. This initial increase can cause:

Indication1

LUPRON DEPOT® (leuprolide acetate for depot suspension) 7.5 mg for 1‑month, 22.5 mg for 3-month, 30 mg for 4‑month, and 45 mg for 6‑month administration are indicated for the palliative treatment of advanced prostatic cancer.

Important Safety Information1

  • LUPRON DEPOT is contraindicated in patients with hypersensitivity to GnRH agonists or any of the excipients in LUPRON DEPOT.
  • LUPRON DEPOT causes an initial increase in serum testosterone (~50% above baseline) during the first few weeks of treatment. This initial increase can cause:
    • Transient worsening of symptoms, or additional signs and symptoms of prostate cancer.
    • Temporary increase in bone pain in a small number of patients, which can be managed symptomatically.
    • Isolated cases of ureteral obstruction and spinal cord compression, which may contribute to paralysis with or without fatal complications. Observe patients with vertebral metastasis and/or urinary tract obstruction closely.
  • Hyperglycemia and increased risk of developing diabetes have been reported in men receiving GnRH agonists. Monitor blood glucose and/or glycosylated hemoglobin (HbA1c) periodically in men receiving a GnRH agonist, and manage hyperglycemia or diabetes.
  • An increased risk of myocardial infarction, sudden cardiac death, and stroke has been reported in association with the use of GnRH agonists in men, although the risk appears low. Evaluate the risks carefully, including cardiovascular risk factors, when determining prostate cancer treatment. Patients receiving a GnRH agonist should be monitored for signs and symptoms of cardiovascular disease and managed appropriately.
  • Androgen deprivation therapy (ADT) may prolong the QT/QTc interval. Consideration should be given to whether the benefits of ADT outweigh the potential risks in patients with congenital long QT syndrome, congestive heart failure, frequent electrolyte abnormalities, and in patients taking drugs known to prolong the QT interval. Correct electrolyte abnormalities and consider periodic monitoring of electrocardiograms and electrolytes.
  • Postmarketing reports of convulsions have been observed in patients on leuprolide acetate therapy, including patients with a history of seizures, epilepsy, cerebrovascular disorders, central nervous system anomalies or tumors, and in patients on concomitant medications associated with convulsions, such as bupropion and SSRIs. Convulsions have also been reported in the absence of any of the conditions mentioned above.
  • Periodic monitoring of serum testosterone and PSA levels is recommended.
  • LUPRON DEPOT may cause fetal harm when administered to a pregnant woman. Advise pregnant patients and females of reproductive potential of the potential risk to the fetus.
  • LUPRON DEPOT may impair fertility in males of reproductive potential.
  • In controlled clinical trials of advanced prostatic cancer patients receiving LUPRON DEPOT, the following adverse events occurred in >10% of patients:
    • LUPRON DEPOT 7.5 mg for 1‑month administration: hot flashes/sweats, general pain, edema, urinary disorders, GI disorders, and respiratory disorders.
    • LUPRON DEPOT 22.5 mg for 3‑month administration: hot flashes/sweats, general pain, testicular atrophy, GI disorders, urinary disorders, injection site reactions, and joint disorders.
    • LUPRON DEPOT 30 mg for 4‑month administration: hot flashes/sweats, injection site reactions, general pain, edema, urinary disorders, joint disorders, GI disorders, asthenia, flu syndrome, skin reactions, and headache.
    • LUPRON DEPOT 45 mg for 6‑month administration: hot flush/flushing, upper respiratory tract infection/influenza-like illness, injection site pain/discomfort, and fatigue/lethargy.

US-LUPR-190307