We would like to share with you the below information regarding Erleada (apalutamide 60 mg) safety profile in patients with Metastatic hormone-sensitive prostate cancer.1
HRQOL* WAS MAINTAINED WITH ERLEADA® WITH NO SUBSTANTIAL DIFFERENCE BETWEEN GROUPS.2
CHANGE IN FACT-P** TOTAL SCORES FROM BASELINE.3
The overall score of the FACT-P ranges from 0 to 156, with higher values indicating a higher HRQoL¶¶2
In the TITAN study, patients’ HRQoL was measured by the FUNCTIONAL ASSESSMENT OF CANCER THERAPY – PROSTATE (FACT-P) QUESTIONNAIRE:2
TREATMENT WITH ERLEADA +ADT
HAS NO NEGATIVE IMPACT ON HRQoL
¶Error bars are standard errors of the mean.
¶¶Patient-reported outcomes for health-related quality of life were assessed by means of the Functional Assessment of Cancer Therapy–Prostate (FACT-P) questionnaire. A change of 6 to 10 points in the FACT-P total score is the minimally important difference.
*HRQoL=Health-related quality of life, **FACT-P=functional assessment of cancer therapyprostate
***ADT=androgen deprivation therapy and add However, this figure presents mean changes in total scores compared with baseline rather than raw total scores. FACT-P, Functional Assessment of Cancer Therapy-Prostate
In this double-blind, phase 3 trial, we randomly assigned patients with metastatic, castrationsensitive prostate cancer to receive apalutamide (240 mg per day) or placebo, added to ADT .
The primary end points were radiographic progression–free survival and overall survival.
A total of 525 patients were assigned to receive apalutamide plus ADT and 527 to receive placebo plus ADT. The median age was 68 years. A total of 16.4% of the patients had undergone
prostatectomy or received radiotherapy for localized disease, and 10.7% had received previous docetaxel therapy; 62.7% had high-volume disease, and 37.3% had low-volume disease. At the first interim analysis, with a median of 22.7 months of follow up, the percentage of patients with radiographic progression–free survival at 24 months was 68.2% in the apalutamide group and 47.5% in the placebo group (hazard ratio for radiographic progression or death, 0.48; 95% confidence interval [CI], 0.39 to 0.60; P<0.001). Overall survival at 24 months was also greater with apalutamide than with placebo (82.4% in the apalutamide group vs. 73.5% in the placebo group; hazard ratio for death, 0.67; 95% CI, 0.51 to 0.89; P = 0.005). The frequency of grade 3 or 4 adverse events was 42.2% in the apalutamide group and 40.8% in the placebo group; rash was more common in the apalutamide group.
1. SmPC of Erleada®.EMA. Last revised 27/1/2020. Last accessed 8/12/2020.
2. Chi KN, Agarwal N, Bjartell A, et al. Apalutamide for Metastatic, Castration-Sensitive Prostate Cancer. N Engl J Med 2019; 381 (1): 13-24.
3. Chi KN, Agarwal N, Bjartell A, et al. Apalutamide for Metastatic, Castration-Sensitive Prostate Cancer. N Engl J Med 2019; 381 (1) : 13-24.Supplementary information.
ERLEADA® IMPORTANT SAFETY INFORMATION
Erleada is indicated
• in adult men for the treatment of non-metastatic castration-resistant prostate cancer (nmCRPC) who are at high risk of developing metastatic disease.
• in adult men for the treatment of metastatic hormone-sensitive prostate cancer (mHSPC) in combination with androgen deprivation therapy (ADT)
The recommended dose is 240 mg (four 60 mg tablets) as an oral single daily dose.
Contraindications Hypersensitivity to the active substance or to any of the excipients.
Women who are or may become pregnant.
Special warnings and precautions for use Seizure:
Erleada is not recommended in patients with a history of seizures or other predisposing factors including, but not limited to, underlying brain injury, recent stroke (within one year), primary brain tumors or brain metastases. If a seizure develops during treatment with Erleada, treatment should be discontinued permanently. The risk of seizure may be increased in patients receiving concomitant medicinal products that lower the seizure threshold. Seizure occurred in 0.2% of patients receiving Erleada in clinical studies. These studies excluded patients with a history of seizure or predisposing factors for seizure.
There is no clinical experience in re-administering Erleada to patients who experienced a seizure.
Falls and fractures:
Falls and fractures occurred in patients receiving Erleada. Patients should be evaluated for fractures and fall risk before starting Erleada and should continue to be monitored and managed for fractures according to established treatment guidelines and use of bone-targeted agents should be considered.
Concomitant use with other medicinal products:
Apalutamide is a potent enzyme inducer and may lead to loss of efficacy of many commonly used medicinal products. A review of concomitant medicinal products should therefore be conducted when apalutamide treatment is initiated. Concomitant use of apalutamide with medicinal products that are sensitive substrates of many metabolising enzymes or transporters should generally be avoided if their therapeutic effect is of large importance to the patient, and if dose adjustments cannot easily be performed based on monitoring of efficacy or plasma concentrations.
Co-administration with warfarin and coumarin-like anticoagulants should be avoided. If Erleada is co-administered with an anticoagulant metabolised by CYP2C9 (such as warfarin or acenocoumarol), additional International Normalized Ratio (INR) monitoring should be conducted.
Recent cardiovascular disease:
Patients with clinically significant cardiovascular disease in the past 6 months including severe/ unstable angina, myocardial infarction, symptomatic congestive heart failure, arterial or venous thromboembolic events (e.g., pulmonary embolism, cerebrovascular accident including transient ischemic attacks), or clinically significant ventricular arrhythmias were excluded from the clinical studies. Therefore, the safety of apalutamide in these patients has not been established. If Erleada is prescribed, patients with clinically significant cardiovascular disease should be monitored for risk factors such as hypercholesterolaemia, hypertriglyceridaemia, or other cardiometabolic disorders.
Patients should be treated, if appropriate, after initiating Erleada for these conditions according to established treatment guidelines.
Androgen deprivation therapy may prolong the QT interval
In patients with a history of or risk factors for QT prolongation and in patients receiving concomitant medicinal products that might prolong the QT interval physicians should assess the benefit-risk ratio including the potential for Torsade de pointes prior to initiating Erleada.
Fertility, pregnancy and lactation:
Contraception in males and females
It is not known whether apalutamide or its metabolites are present in semen. Erleada may be harmful to a developing fetus. For patients having sex with female partners of reproductive potential, a condom should be used along with another highly effective contraceptive method during treatment and for 3 months after the last dose of Erleada.
Erleada is contraindicated in women who are or may become pregnant. Based on its mechanism of action, Erleada may cause fetal harm when administered during pregnancy. There are no data available from the use of Erleada in pregnant women. Animal reproductive studies have not been conducted with Erleada.
It is unknown whether apalutamide/metabolites are excreted in human milk. A risk to the suckling child cannot be excluded. Erleada should not be used during breast-feeding.
Based on animal studies, Erleada may decrease fertility in males of reproductive potential.
Effects on ability to drive and use machines
Erleada has no or negligible influence on the ability to drive and use machines. However, seizures have been reported in patients taking Erleada. Patients should be advised of this risk in regards to driving or operating machines.
Summary of the safety profile
The most common adverse reactions are fatigue (30%), skin rash (24% of any grade and 5% Grade 3 or 4), weight decreased (16%), arthralgia (16%), and fall (16%). Other important adverse reactions include fractures (12%) and hypothyroidism (8%).
Tabulated list of adverse reactions Adverse reactions observed during clinical studies are listed below by frequency category.
Frequency categories are defined as follows: very common (≥ 1/10); common (≥ 1/100 to < 1/10); uncommon (≥ 1/1,000 to < 1/100); rare (≥ 1/10,000 to < 1/1,000); very rare (< 1/10,000) and not known (frequency cannot be estimated from the available data). Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness.
Table 1: Adverse reactions identified in clinical studies
|System organ class||Adverse reaction and frequency|
|Endocrine disorders||common: hypothyroidism*|
|Metabolism and nutrition disorders|
|Nervous system disorders||uncommon: seizure|
|Cardiac disorders||not known: QT prolongation|
|Skin and subcutaneous tissue disorders||very common: skin rash**|
|Musculoskeletal and connective tissue|
|very common: fracture+|
very common: arthralgia
|General disorders and administration site conditions||very common: fatigue|
|Investigations||very common: weight decreased|
|Injury, poisoning and procedural|
|very common: fall|
* Includes hypothyroidism, blood thyroid stimulating hormone increased, thyroxine decreased, autoimmune thyroiditis, thyroxine free decreased, tri-iodothyronine decreased
** See “Skin rash” under “Description of selected adverse reactions”
+ Includes rib fracture, lumbar vertebral fracture, spinal compression fracture, spinal fracture, foot fracture, hip fracture, humerus fracture, thoracic vertebral fracture, upper limb fracture, fractured sacrum, hand fracture, pubis fracture, acetabulum fracture, ankle fracture, compression fracture, costal cartilage fracture, facial bones fracture, lower limb fracture, osteoporotic fracture, wrist fracture, avulsion fracture, fibula fracture, fractured coccyx, pelvic fracture, =radius fracture, sternal fracture, stress fracture, traumatic fracture, cervical vertebral fracture, femoral neck fracture, tibia fracture. See below.
Reporting of suspected adverse reactions:
Reporting suspected adverse reactions after authorisation of the medicinal product is important.
It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the national reporting system listed in Appendix V.
- Always read the full prescribing information.
- Healthcare professionals are asked to report any suspected adverse reactions to Egyptian pharmacovigilance center (EPVC).
- MOH leaflet approval date: 11/2020.