Can Nubeqa (darolutamide) cause neutropenia and thrombocytopenia?

Nubeqa and Hematologic Toxicity

Nubeqa (darolutamide) does cause neutropenia and thrombocytopenia, though these adverse events occur at relatively low rates compared to many other cancer therapies. According to the FDA label, decreased neutrophil count occurs in 20% of patients (4% grade 3-4) in non-metastatic castration-resistant prostate cancer, while thrombocytopenia is not specifically listed as a common adverse event in this population 1. However, when combined with docetaxel for metastatic hormone-sensitive prostate cancer, neutropenia becomes substantially more common at 49% overall (33% grade 3-4) 1.

Non-Metastatic Castration-Resistant Prostate Cancer (nmCRPC)

In the ARAMIS trial for nmCRPC, hematologic toxicity with Nubeqa monotherapy was modest:

• Neutropenia: 20% all grades, 4% grade 3-4 (compared to 9% all grades, 0.6% grade 3-4 with placebo) 1
• Thrombocytopenia: Not listed among common adverse reactions (>2% with ≥2% increase vs placebo), suggesting rates were minimal 1
• Anemia: Not specifically reported as a common adverse event in this setting 1

The median duration of exposure in ARAMIS was substantial, indicating these toxicities did not commonly lead to treatment discontinuation 1.

Metastatic Hormone-Sensitive Prostate Cancer (mHSPC) with Docetaxel

When Nubeqa is combined with docetaxel in the ARASENS trial, hematologic toxicity increases significantly, primarily driven by docetaxel:

• Neutropenia: 49% all grades, 33% grade 3-4 (vs 44% all grades, 31% grade 3-4 with placebo plus docetaxel) 1
• Thrombocytopenia: Not specifically listed in the adverse reaction table, but febrile neutropenia occurred in 6% as a serious adverse reaction 1
• Anemia: 72% all grades, 6% grade 3-4 (vs 71% all grades, 7% grade 3-4 with placebo plus docetaxel) 1
• Lymphopenia: 52% all grades, 12% grade 3-4 (vs 49% all grades, 13% grade 3-4 with placebo plus docetaxel) 1

The addition of Nubeqa to docetaxel resulted in only a modest incremental increase in neutropenia rates (2% absolute increase in grade 3-4) compared to docetaxel alone 1.

Clinical Management Considerations

Monitor complete blood counts regularly, particularly when combining Nubeqa with docetaxel:

• Baseline CBC should be obtained before initiating therapy 1
• More frequent monitoring is warranted during the first 3-6 months when combining with docetaxel, as this is when myelosuppression typically peaks 2
• Febrile neutropenia occurred in 6% of patients receiving Nubeqa with docetaxel and was managed with dose interruptions in 2.1% of cases 1

Dose modifications for hematologic toxicity:

• Dosage interruptions occurred in 23% of patients on Nubeqa with docetaxel, with febrile neutropenia being a common reason (2.1%) 1
• Permanent discontinuation due to adverse reactions occurred in 14% overall, though hematologic toxicity was not the primary driver 1
• Growth factor support (G-CSF) can be considered for persistent neutropenia, particularly when combined with chemotherapy 2

Key Distinctions from Other Agents

Nubeqa's hematologic toxicity profile is substantially milder than many other cancer therapies:

• Unlike tyrosine kinase inhibitors for CML, which cause grade 3-4 neutropenia in 17-34% and thrombocytopenia in 10-47% 2, Nubeqa monotherapy causes grade 3-4 neutropenia in only 4% 1
• Unlike CAR T-cell therapies for multiple myeloma, which cause grade 3-4 neutropenia in 64-95% and thrombocytopenia in 21-63% 2, Nubeqa's rates are markedly lower 1
• The hematologic toxicity is primarily attributable to docetaxel when used in combination, with Nubeqa adding minimal incremental risk 1

Common Pitfalls

Do not attribute all cytopenias to Nubeqa when used with docetaxel - the chemotherapy is the primary driver of myelosuppression, and the incremental contribution of Nubeqa is modest 1. Avoid unnecessary dose reductions of Nubeqa for mild cytopenias that are likely docetaxel-related and manageable with standard supportive care 1.