Abiraterone (Page 10 of 12)

LATITUDE: Patients with metastatic high-risk CSPC

In LATITUDE (NCT01715285), 1199 patients with metastatic high-risk CSPC were randomized 1:1 to receive either abiraterone acetate orally at a dose of 1,000 mg once daily with prednisone 5 mg once daily (N=597) or placebos orally once daily (N=602). High-risk disease was defined as having at least two of three risk factors at baseline: a total Gleason score of ≥8, presence of ≥3 lesions on bone scan, and evidence of measurable visceral metastases. Patients with significant cardiac, adrenal, or hepatic dysfunction were excluded. Patients continued treatment until radiographic or clinical disease progression, unacceptable toxicity, withdrawal or death. Clinical progression was defined as the need for cytotoxic chemotherapy, radiation or surgical treatment for cancer, pain requiring chronic opioids, or ECOG performance status decline to ≥3.

Patient demographics were balanced between the treatment arms. The median age was 67 years among all randomized subjects. The racial distribution of patients treated with abiraterone acetate was 69% Caucasian, 2.5% Black, 21% Asian, and 8.1% Other. The ECOG performance status was 0 for 55%, 1 for 42%, and 2 for 3.5% of patients. Baseline pain assessment was 0-1 (asymptomatic) in 50% of patients, 2-3 (mildly symptomatic) in 23% of patients, and ≥4 in 28% of patients as defined by the Brief Pain Inventory-Short Form (worst pain over the last 24 hours).

A major efficacy outcome was overall survival. The pre-specified interim analysis after 406 deaths showed a statistically significant improvement in OS in patients on abiraterone acetate with prednisone compared to those on placebos. Twenty-one percent of patients on the abiraterone acetate arm and 41% of patients on the placebos arm received subsequent therapies that may prolong OS in metastatic CRPC. An updated survival analysis was conducted when 618 deaths were observed. The median follow-up time was 52 months. Results from this analysis were consistent with those from the pre-specified interim analysis (Table 10 and Figure 4). At the updated analysis, 29% of patients on the abiraterone acetate arm and 45% of patients on the placebos arm received subsequent therapies that may prolong OS in metastatic CRPC.

Table 10: Overall Survival of Patients Treated with Either Abiraterone Acetate or Placebos in LATITUDE (Intent-to-Treat Analysis)

Abiraterone Acetate with Prednisone

(N=597)

Placebos

(N=602)

Overall Survival 1
Deaths (%) 169 (28%) 237 (39%)
Median survival (months) NE (NE, NE) 34.7 (33.1, NE)

(95% CI) p-value 2

<0.0001
Hazard ratio (95% CI) 3 0.62 (0.51, 0.76)
Updated Overall Survival
Deaths (%) 275 (46%) 343 (57%)
Median survival (months) (95% CI) 53.3 (48.2, NE) 36.5 (33.5, 40.0)
Hazard ratio (95% CI) 3 0.66 (0.56, 0.78)

NE=Not estimable

1 This is based on the pre-specified interim analysis

2 p value is from log-rank test stratified by ECOG PS score (0/1 or 2) and visceral (absent or present).

3 Hazard Ratio is derived from a stratified proportional hazards model. Hazard ratio <1 favors abiraterone acetate with prednisone.

Figure 4: Kaplan-Meier Plot of Overall Survival; Intent-to-treat Population in LATITUDE Updated Analysis

Overall Survival, Intent-to-Treat Population in LATITUDE
(click image for full-size original)

The major efficacy outcome was supported by a statistically significant delay in time to initiation of chemotherapy for patients in the abiraterone acetate arm compared to those in the placebos arm. The median time to initiation of chemotherapy was not reached for patients on abiraterone acetate with prednisone and was 38.9 months for patients on placebos (HR = 0.44; 95% CI: [0.35, 0.56], p < 0.0001).

16 HOW SUPPLIED/STORAGE AND HANDLING

Abiraterone Acetate Tablets, USP 250 mg – Uncoated tablets

Abiraterone acetate tablets, USP are available as white to off-white, oval tablets debossed with “WW597” on one side.

NDC 72789-213-98 120 tablets available in high-density polyethylene bottles


Storage and Handling

Store at 20°C to 25°C (68°F to 77°F); excursions permitted in the range from 15°C to 30°C (59°F to 86°F) [see USP Controlled Room Temperature].

Keep out of reach of children.

Based on its mechanism of action, abiraterone acetate tablets may harm a developing fetus. Women who are pregnant or women who may be pregnant should not handle abiraterone acetate 250 mg uncoated tablets or other abiraterone acetate tablets if broken, crushed, or damaged without protection, e.g., gloves [see Use in Specific Populations (8.1)] .

17 PATIENT COUNSELING INFORMATION

Advise the patient to read the FDA-approved patient labeling (Patient Information)

Hypokalemia, Fluid Retention, and Cardiovascular Adverse Reactions

  • Inform patients that abiraterone acetate tablets are associated with hypertension, hypokalemia, and peripheral edema that may lead to QT prolongation and Torsades de Pointes in patients who develop hypokalemia while taking abiraterone acetate tablets. Advise patients that their blood pressure, serum potassium and signs and symptoms of fluid retention will be monitored clinically at least monthly. Advise patients to adhere to corticosteroids and to report symptoms of hypertension, hypokalemia, or edema to their healthcare provider [see Warnings and Precautions (5.1)] .

Adrenocortical Insufficiency

  • Inform patients that abiraterone acetate tablets with prednisone is associated with adrenal insufficiency. Advise patients to report symptoms of adrenocortical insufficiency to their healthcare provider [see Warnings and Precautions (5.2)].

Hepatotoxicity

  • Inform patients that abiraterone acetate tablets are associated with severe hepatotoxicity. Inform patients that their liver function will be monitored using blood tests. Advise patients to immediately report symptoms of hepatotoxicity to their healthcare provider [see Warnings and Precautions (5.3)] .

Hypoglycemia

  • Inform patients that severe hypoglycemia has been reported when abiraterone acetate was administered to patients with pre-existing diabetes who were receiving medications containing thiazolidinediones (including pioglitazone) or repaglinide, antidiabetic drugs. Advise patients with diabetes to monitor glucose levels during and after treatment with abiraterone acetate [see Warnings and Precautions (5.6) and Drug Interactions (7.2)] .

Use in Combination with Radium Ra 223 Dichloride

  • Advise patients that radium Ra 223 dichloride showed an increase in mortality and an increased rate of fracture when used in combination with abiraterone acetate tablets plus prednisone/prednisolone. Inform patients to speak with their healthcare provider about any other medications or treatment they are currently taking for prostate cancer [see Warnings and Precautions (5.4)] .

Dosing and Administration

  • Inform patients that abiraterone acetate is taken once daily with prednisone (twice daily according to their healthcare provider’s instructions) and to not interrupt or stop either of these medications without consulting their healthcare provider.
  • Inform patients receiving GnRH therapy that they need to maintain this treatment during the course of treatment with abiraterone acetate tablets.
  • Instruct patients to take abiraterone acetate tablets as a single dose once daily on an empty stomach. Instruct patients to not eat food 2 hours before and 1 hour after taking abiraterone acetate. Abiraterone acetate taken with food causes increased exposure and may result in adverse reactions. Instruct patients to swallow tablets whole with water and not to crush or chew the tablets [see Dosage and Administration (2.3)].
  • Inform patients that if they miss a dose of abiraterone acetate tablets or prednisone, they should take their normal dose the following day. If more than one daily dose is skipped, inform patients to contact their healthcare provider [see Dosage and Administration (2.3)].

Embryo-Fetal Toxicity

  • Inform patients that abiraterone acetate tablets may harm a developing fetus and can cause loss of pregnancy.
  • Advise males with female partners of reproductive potential to use effective contraception during treatment and for 3 weeks after the final dose of abiraterone acetate tablets [see Use in Specific Populations (8.1)].
  • Advise females who are pregnant or women who may be pregnant not to handle abiraterone acetate 250 mg uncoated tablets if broken, crushed, or damaged without protection, e.g., gloves [see Use in Specific Populations (8.1) and How Supplied/Storage and Handling (16)].

Infertility

  • Advise male patients that abiraterone acetate tablets may impair fertility [see Use in Specific Populations (8.3)].

Distributed by: West-Ward
Pharmaceuticals Corp.
Eatontown, NJ 07724 USA

Manufactured by:
The Arab Pharmaceuticals Manufacturing Company P.O. Box 41, Sahab — Jordan

Revised September 2021

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