SUMMARY  

• Postmarketing cases of interstitial lung disease (ILD) or pneumonitis, including fatal cases, have been reported with ERLEADA.^1-6 In case of acute onset and/or unexplained worsening of pulmonary symptoms, treatment with ERLEADA should be interrupted pending further investigation of these symptoms. If ILD or pneumonitis is diagnosed, ERLEADA should be discontinued.¹ For additional considerations and data from the pivotal phase 3 clinical studies, please refer to local labeling.

Post Marketing Safety Information

Fang et al (2023)² assessed the real-world postmarketing safety profile of ERLEADA using United States Food and Drug Administration Adverse Event Reporting System (FAERS) data.  Disproportionality analyses were used to identify adverse event (AE) signals in reports where ERLEADA was documented as primary or secondary suspect from the first quarter of 2018 to the first quarter of 2022. Preferred Terms (PTs) by the Medical Dictionary for Regulatory Activities (MedDRA) and reporting odds ratio (ROR) were used for identifying signals indicating a potentially increased risk of drug-associated AEs.

• Of 4156 total AE reports, 50 AEs of ILD were reported with a ROR of 7.61 (95% confidence interval, 5.76-10.06).

Wu et al (2023)³ conducted disproportionality analyses in a retrospective, observational, pharmacovigilance study to assess AEs of ILD reported in patients with prostate cancer receiving hormone therapy using FAERS data from January 2004-December 2020. The 85,403 cases were divided into 3 groups based on primary suspected drugs: hormone therapy group (the research group, 628 ILD cases/69,894 cases), taxane group (positive control group, 158 ILD cases/2302 cases), and other primary suspected drug group (negative control group, 72 ILD cases/13,207 cases). Of the total ILD cases in the hormone therapy group, there were 394 ILD cases (62.74%) in Japan. ROR was used to detect the association between ILD AEs and target drugs.

• Results for the ERLEADA monotherapy analysis indicated significant association: 9 AEs/791 total events, 1.14% proportion, ROR: 1.94 (95% CI, 1.01–3.75) in Japanese population.
• For the time to event onset, a total of 429 prostate cancer cases with AEs of ILD were reported with sufficient data (n=319 in the hormone therapy group), of which 6 AEs were reported for ERLEADA with a median time of 33 days (interquartile range, 19-77 days).

Case Reports

Case reports from Japan were identified in the literature describing patients who developed ILD within 3 months of initiating ERLEADA. Patients were >70 years of age and had a previous history of smoking. At the onset of ILD symptoms, patients discontinued ERLEADA and received supportive care and intravenous methylprednisolone. None of the patients were readministered ERLEADA following the diagnosis of drug-induced ILD.^4,5

Two additional case reports of European patients with metastatic castration-sensitive prostate cancer (mCSPC) that developed ILD were identified. The first patient was a 55 year old male that had his dose reduced to 180 mg per day 2 months after initiating ERLEADA due to the appearance of grade 3 skin rash. One month later, the patient experienced cough and progressive respiratory distress. The second patient was a 73 year old male and experienced 2 months of cough, mucous expectoration, and weight loss 6 months after initiating ERLEADA. For both patients, ERLEADA-induced ILD was diagnosed based on test findings and the medication was discontinued. High-dose corticosteroids were used for treatment and resolution of prior pulmonary signs was observed. Neither patient was readministered ERLEADA.⁶

Literature Search

A literature search of MEDLINE^®, Embase^®, BIOSIS Previews^®, and Derwent Drug File (and/or other resources, including internal/external databases) was conducted on 29 July 2024. Summarized in this response are relevant data limited to the FAERS database and case reports.