When is Keytruda (pembrolizumab) used for advanced or metastatic prostate cancer?

From the Guidelines

Keytruda (pembrolizumab) is used for advanced or metastatic prostate cancer specifically in patients who have microsatellite instability-high (MSI-H), mismatch repair deficient (dMMR), or high tumor mutational burden (TMB-H) tumors that have progressed following prior treatment, as supported by the most recent guidelines 1.

Key Considerations

• The use of Keytruda in prostate cancer is based on its approval for unresectable or metastatic MSI-H or dMMR solid tumors, with an objective response rate of 40% in a cohort that included non-colorectal cancers, including prostate cancer 1.
• The typical dosing of Keytruda for this indication is 200 mg administered as an intravenous infusion over 30 minutes every 3 weeks, or alternatively 400 mg every 6 weeks, continuing until disease progression or unacceptable toxicity occurs.
• Patients should undergo biomarker testing to confirm MSI-H, dMMR, or TMB-H status before starting treatment, as the prevalence of MMR deficiency in metastatic CRPC is estimated at 2%–5% 1.

Important Safety Information

• The most common adverse events from pembrolizumab are fatigue, pruritus, diarrhea, anorexia, constipation, nausea, rash, fever, cough, dyspnea, and musculoskeletal pain, with potential immune-mediated side effects including colitis, hepatitis, endocrinopathies, pneumonitis, or nephritis 1.
• Patients receiving Keytruda should be monitored for immune-related adverse events, which can affect multiple organ systems and may require corticosteroid treatment or therapy interruption.

Clinical Evidence

• The KEYNOTE-199 study, a multicohort, open-label phase II study, assessed pembrolizumab in patients with mCRPC and prior treatment with docetaxel and at least one novel hormonal therapy, showing an overall response rate of 5% in PD-L1–positive patients and 3% in PD-L1–negative patients 1.
• The non-randomized phase Ib KEYNOTE-028 trial included 23 patients with advanced, progressive prostate cancer, showing an objective response rate of 17.4% and stable disease in 34.8% of patients 1.

From the Research

Keytruda (Pembrolizumab) for Advanced or Metastatic Prostate Cancer

• Keytruda (pembrolizumab) is used for advanced or metastatic prostate cancer in specific cases, such as:
  • Patients with high levels of microsatellite instability or high tumor mutational burden 2
  • Patients with mismatch repair deficiency (MMRd) or microsatellite instability (MSI-H) 3, 4
• The use of pembrolizumab in prostate cancer is based on the presence of certain biomarkers, such as PD-L1 expression, although PD-L1 positivity does not predict response to pembrolizumab in this disease 5, 4
• Pembrolizumab has been evaluated in combination with other therapies, such as docetaxel and prednisone, in patients with metastatic castration-resistant prostate cancer (mCRPC) 6
• The efficacy and safety of pembrolizumab in prostate cancer patients have been assessed in several clinical trials, including the KEYNOTE-028, KEYNOTE-365, and KEYLYNK-010 studies 5, 4, 6

Patient Selection

• Patient selection for pembrolizumab treatment in prostate cancer is crucial and should be based on molecular tumor profiling and the presence of specific biomarkers 2, 3
• Patients with advanced or metastatic prostate cancer who have failed other treatments, such as androgen deprivation therapy, chemotherapy, or targeted therapies, may be considered for pembrolizumab treatment 5, 6

Ongoing Research

• Ongoing research is focused on developing innovative combination strategies and identifying additional biomarkers to improve outcomes in prostate cancer patients treated with pembrolizumab 4
• Further investigation is needed to fully understand the potential benefits and limitations of pembrolizumab in prostate cancer treatment 6