ZYTIGA - COVID-19, Respiratory, and Other Infections

SUMMARY

• No prospective clinical studies evaluating the efficacy and safety of ZYTIGA in patients with active infections, including novel coronavirus disease 2019 (COVID-19), have been published. In addition, no published data were identified regarding the use of a COVID-19 vaccine in patients receiving ZYTIGA. For more information on the use of vaccines and treatments for COVID-19, please contact the product manufacturers directly.
• In a retrospective, population-based, epidemiological study that evaluated the effect of androgen-inhibiting therapies on COVID-19 outcomes (hospitalization, intensive care, and death), patients with prostate cancer who received androgen-deprivation therapy (ADT) plus ZYTIGA or enzalutamide had a higher risk of mortality due to COVID-19 (hazard ratio [HR], 2.51; 95% confidence interval [CI], 1.52-4.16) after adjustment for age and comorbidities. No difference in outcomes was observed between patients receiving ZYTIGA plus ADT and patients receiving enzalutamide plus ADT (Table: Outcomes in Patients in Group 3 Receiving Enzalutamide or ZYTIGA).¹
• In a retrospective study of 151 patients with metastatic prostate cancer who developed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection while receiving active systemic anticancer therapy, 47 patients required hospitalization for COVID-19 symptom management. Hospitalization rates were 31.2% in the metastatic castration-resistant prostate cancer (mCRPC) group and 30.7% in the metastatic hormone-sensitive prostate cancer (mHSPC) group. Overall, 19 patients (12.6%) died due to SARS-CoV-2 infection. Sixteen patients (10.6%) recovered from the infection but did not resume or continue their ongoing anticancer therapy, and 116 patients (76.8%) resumed or maintained treatment after recovery.²
• ZYTIGA is indicated in combination with prednisone/prednisolone.³ Patients receiving ZYTIGA should also receive a gonadotropin-releasing hormone (GnRH) analog concurrently or should have had a bilateral orchiectomy.^4-6 For more information regarding GnRH analog therapy, please contact the manufacturer directly.
• Data to assess incidence of COVID-19 in patients with cancer, including patients with prostate cancer receiving ADT, have been published.^7-14

COVID-19 Prophylaxis or Infection in Patients Receiving ZYTIGA plus Prednisone

• If a patient is suspected to have been exposed to COVID-19, but is asymptomatic, providers should follow local and institutional guidelines to weigh risk vs benefit of the individual patient’s treatment with ZYTIGA plus prednisone based on the nature and status of the patient’s underlying cancer, comorbidities, concomitant medications, and the potential risks associated with COVID-19 infection.
• For prophylaxis, or if a patient has a confirmed COVID-19 infection, physicians should consider the risk vs benefit of continuing ZYTIGA based on the nature and status of the patient’s underlying cancer, comorbidities, and the potential risks associated with the COVID-19 infection. Providers should refer to product labeling for additional information, including pharmacokinetics, safety, dosage & administration, dose modifications, monitoring, and drug-drug interactions for other medications used concomitantly in the prevention or management of COVID-19 infection.¹⁵

Select COVID-19 Resources for Providers Treating Patients with Cancer

Please note: this is not a complete list of publicly available resources pertaining to this topic.

• The Centers for Disease Control and Prevention (CDC) provides clinical care considerations for clinicians caring for patients with confirmed infection and SARS-CoV-2.¹⁶
  • Interventions should be based on patient presentation and the clinical judgment of the treating physician. For the latest information from the CDC, visit: COVID-19.
• The American Cancer Society (ACS) and the American Society of Clinical Oncology (ASCO) recognize that cancer patients and cancer survivors often have weakened immune systems, increasing their risk for serious illness from infections such as the coronavirus. ASCO recommends that oncologists and health care teams should discuss with their patients how best to protect against infections, such as coronavirus.^17,18
• Additional cancer organizations, including the National Comprehensive Cancer Network (NCCN) and the European Society for Medical Oncology (ESMO), have published resources for healthcare professionals, visit: NCCN COVID-19 Resources.
• For the latest global information and guidance from the World Health Organization (WHO) regarding the current outbreak of COVID-19, including daily updates, visit: Coronavirus Disease (COVID-19) Pandemic.

COVID 19

Epidemiological Analysis of the Risk Associated with Androgen Inhibition in COVID-19 Outcomes

A retrospective, population-based, epidemiological study was conducted to evaluate the effect of androgen-inhibiting therapies on COVID-19 outcomes (hospitalization, intensive care, and death) in patients with prostate cancer from the Swedish national registers (N=7894).¹

This analysis was performed in the age group of 50-81 years (n=5824). Patients were categorized as follows: those who received a single anti-androgen treatment (group 1; n=358), who received surgical or chemical castration (ADT; group 2; n=334), who received ADT plus ZYTIGA or enzalutamide (group 3; n=152), and prostate cancer patients with no ongoing or prior hormonal therapy (control group, n=4980). Patients in groups 1, 2, and 3 were older and had higher comorbidity scores than those in the control group. Patients in group 3 had a significantly higher comorbidity score than those in group 2 (P<0.001). Unadjusted analyses showed that the risk for hospitalization, need for intensive care (only group 1), and death due to COVID-19 were higher in patients who received androgen-inhibition treatment. After adjusting for age and comorbidities, patients in group 3 had a higher risk of mortality due to COVID-19 (HR, 2.51; 95% CI, 1.52-4.16).¹ No difference in outcomes was observed between patients in group 3 who received ZYTIGA plus ADT and patients who received enzalutamide plus ADT (Table: Outcomes in Patients in Group 3 Receiving Enzalutamide or ZYTIGA).¹⁹

Treatment Continuation and Long-term Oncological Outcomes Following SARS-CoV-2 Infection

A retrospective study evaluated a consecutive series of 151 patients with metastatic prostate cancer who developed SARS-CoV-2 infection while receiving one active systemic anticancer therapy between January 2020 and December 2022 across 10 Italian hospitals. Hospitalization for the management of COVID-19 infection symptoms was required in 47 patients, with comparable hospitalization rates of 31.2% in the mCRPC group and 30.7% in the mHSPC group. Overall, 19 patients (12.6%) died due to SARS-CoV-2 infection. Sixteen patients (10.6%) recovered from the infection but did not resume or continue their ongoing anticancer therapy; 116 patients (76.8%) resumed or maintained treatment after recovery.²

Among patients with mCRPC who developed SARS-CoV-2 infection, ZYTIGA plus ADT was being received by 30 patients (45.5%) in the first-line setting, 6 patients (24.0%) in the second-line setting, and 2 patients (5.9%) in the third-or-later-line setting. Following COVID-19 infection, 1 patient (2.6%) permanently discontinued ZYTIGA plus ADT for reasons other than death, and 33 patients (86.8%) resumed or maintained treatment after recovery. Treatment discontinuation due to death was reported in 4 patients (10.5%) receiving ZYTIGA plus ADT. Among patients receiving first-line abiraterone, the median postinfection progression-free survival (piPFS) was 12.5 months (95% CI, 4.3-20.8). The median postinfection overall survival (piOS) and overall survival (OS) were not reached (NR). No statistically significant differences were observed in piPFS, piOS, or OS (not significant for all comparisons). Eighteen patients (14.4%) died due to SARS-CoV-2 infection.²

Among patients with mHSPC who developed SARS‑CoV‑2 infection, 1 patient (3.8%) was receiving ZYTIGA plus ADT at the time of infection. Following COVID‑19 infection, 1 patient (100%) resumed or maintained treatment after recovery. At a median follow-up of 24.8 months, the median piPFS among patients with mHSPC who resumed or maintained their preinfection anticancer treatment was 17.4 months (95% CI, 9.8-25). The median piOS was not reached in patient with mCSPC who resumed their preinfection anticancer treatment, and the projected 4-year survival rate was 59.8%. The median OS was 122 months (95% CI, 47-197). No statistically significant differences in piPFS, piOS, or OS were observed according to treatment agent. One patient (3.8%) died due to SARS-CoV-2 infection.²

RESPIRATORY AND OTHER INFECTIONS

Concomitant Use with Corticosteroids and GnRH Analogs

Abiraterone acetate is converted in vivo to abiraterone, a 17α-hydroxylase/C17,20-lyase (CYP17) inhibitor, and is indicated in combination with prednisone/prednisolone. Mineralocorticoid effects, such as hypertension, hypokalemia and edema, resulting from CYP17 inhibition may be ameliorated by coadministration with a corticosteroid, which lowers adrenocorticotropic hormone (ACTH) and steroids upstream of the CYP17 blockade.¹

The efficacy and safety of ZYTIGA plus prednisone was studied in 3 phase 3, randomized, double-blind, placebo-controlled, multicenter clinical studies included in product labeling (COU-AA-301, COU-AA-302, and LATITUDE):^4-6,20,21

• ZYTIGA was administered as 1000 mg orally (PO) once daily in all studies.
• COU-AA-301 and COU-AA-302 evaluated ZYTIGA plus prednisone/prednisolone 5 mg PO twice daily in patients with mCRPC who received prior docetaxel or were chemotherapy naïve, respectively.

• LATITUDE evaluated ZYTIGA plus a lower dose of prednisone/prednisolone, 5 mg PO once daily, in patients with metastatic high-risk castration-sensitive prostate cancer (CSPC).
• All patients in these studies received a GnRH analog or had prior bilateral orchiectomy. For more information regarding GnRH analog therapy, please contact the manufacturer directly.
• Patients with active and uncontrolled infection or other medical conditions that would make prednisone/prednisolone use contraindicated were excluded from COU-AA-301, COU-AA-302, and the LATITUDE clinical studies.

Long-term use of moderate or high corticosteroid doses (eg, ≥20 mg/day of prednisone) has an established adverse event profile, including infections.²² The rates of infection, dosing modifications (including dose reductions and interruptions) for infection, and discontinuations due to infection for ZYTIGA and prednisone/prednisolone are included in the 3 phase 3 study summaries below: COU-AA-301, COU-AA-302, and LATITUDE.^23-25

Phase 3 COU-AA-301 Study

COU-AA-301was a phase 3, randomized, double-blind, placebo-controlled, multinational study evaluating the use of ZYTIGA 1000 mg PO daily plus prednisone 5 mg PO twice daily vs placebo plus prednisone in patients with mCRPC and disease-progression after docetaxel-based chemotherapy (N=1195). Patients were excluded from the study if they had serious or uncontrolled coexistent nonmalignant disease, including active and uncontrolled infection.^4,20

Infection-related deaths that occurred in the study included 1 patient each in the ZYTIGA plus prednisone group for enterococcal infection, sepsis, septic shock, staphylococcal infection, and urosepsis and 1 patient for urosepsis and 2 patients for pneumonia in the placebo plus prednisone group.²³ The incidence of infections that occurred with a ≥2% absolute increase in frequency and study drug dose modifications (including dose reductions and interruptions) and discontinuation in the ZYTIGA plus prednisone group compared to the placebo plus prednisone group in the safety population. See tables: Infections in Phase 3 COU-AA-301 Study and Study Drug Dose Modifications and Discontinuation due to the Treatment Emergent Adverse Event-Infection in Phase 3 COU-AA-301 Study.

Efficacy and safety analyses were not performed separately for patients with a concurrent infection in the COU-AA-301 study.

Phase 3 COU-AA-302 Study

COU-AA-302 was a phase 3, randomized, double-blind, placebo-controlled, multinational study evaluating the use of ZYTIGA 1000 mg PO daily plus prednisone 5 mg PO twice daily vs placebo plus prednisone in asymptomatic or mildly symptomatic patients with chemotherapy-naïve mCRPC (N=1088). Patients were excluded from the study if they had active infection or other medical condition that would make prednisone/prednisolone use contraindicated.⁵

Infection-related deaths that occurred in the study included 2 patients each for pneumonia and respiratory tract infection and 1 patient for lung infection in the ZYTIGA plus prednisone group and none in the placebo plus prednisone group.²⁴ The incidence of infections that occurred in ≥5% of patients with a ≥2% absolute increase in frequency and study drug dose modifications and discontinuation in the ZYTIGA plus prednisone group compared to the placebo plus prednisone group in the safety population. See tables: Infections in Phase 3 COU-AA-302 Study and Study Drug Dose Modifications and Discontinuation due to the Treatment Emergent Adverse Event-Infection in Phase 3 COU-AA-302 Study.

Efficacy and safety analyses were not performed separately for patients with a concurrent infection in the COU-AA-302 study.

Phase 3 LATITUDE Study

LATITUDE was a phase 3, randomized, double-blind, placebo-controlled, multinational study evaluating the use of ZYTIGA 1000 mg PO daily plus prednisone 5 mg PO once daily with ADT vs placebos with ADT in patients with newly diagnosed, high-risk metastatic CSPC (N=1199). Patients were excluded from the study if they had active infection or other medical condition that would make prednisone use contraindicated.^6,21

Infection-related deaths that occurred in the study included 3 patients for pneumonia and 1 patient each for lower respiratory tract infection and lung infection in the ZYTIGA plus prednisone group and 1 patient each for pneumonia, bronchopneumonia, and urosepsis and 2 patients for sepsis in the placebo plus prednisone group.²⁵ The incidence of infections that occurred in ≥5% of patients with a ≥2% absolute increase in frequency and study drug dose modifications and discontinuation in the ZYTIGA plus prednisone group compared to the placebos plus prednisone group in the safety population. See tables: Infections in Phase 3 LATITUDE Study and Study Drug Dose Modifications and Discontinuation due to the Treatment Emergent Adverse Event-Infection in Phase 3 LATITUDE Study.

Efficacy and safety analyses were not performed separately for patients with a concurrent infection in the LATITUDE study.

Literature Search

A literature search of MEDLINE^®, Embase^®, BIOSIS Previews^®, and Derwent Drug File (and/or other resources, including internal/external databases) pertaining to this topic was conducted on 20 July 2026.