Can OPDIVO (nivolumab) effectively treat prostate cancer?

OPDIVO (Nivolumab) Is Not Effective for Treating Prostate Cancer

OPDIVO (nivolumab) is not currently recommended as an effective treatment for prostate cancer as it lacks FDA approval and sufficient evidence supporting its use as monotherapy for this indication.

Current Evidence on Nivolumab for Prostate Cancer

• Nivolumab (OPDIVO) has received FDA approval for several cancer types including bladder cancer, kidney cancer, and other solid tumors, but not specifically for prostate cancer 1.
• In bladder cancer, nivolumab has shown efficacy as a second-line therapy after platinum-based chemotherapy with objective response rates of approximately 19.6% 1.
• For kidney cancer, nivolumab is listed as a category 2A option for non-clear cell renal cell carcinoma (nccRCC) 1.

Limited Evidence in Prostate Cancer

• Small studies have evaluated nivolumab in prostate cancer, primarily in combination with other agents rather than as monotherapy:
  • A phase II trial combining nivolumab with ipilimumab in AR-V7-expressing metastatic prostate cancer showed limited efficacy in the overall population with only 13% PSA response rate and 25% objective response rate 2.
  • The CheckMate 9KD trial evaluated nivolumab plus rucaparib for metastatic castration-resistant prostate cancer (mCRPC), showing modest activity primarily in patients with homologous recombination deficiency (HRD)-positive tumors, particularly those with BRCA1/2 mutations 3.
  • A phase II trial of a DNA vaccine (pTVG-HP) with nivolumab in non-metastatic prostate cancer showed no complete PSA responses, though 21% of patients had PSA decline >50% 4.

More Promising Approaches for Prostate Cancer

• Current NCCN guidelines do not include nivolumab as a recommended treatment option for prostate cancer 1.
• For metastatic urothelial carcinoma (bladder cancer), nivolumab in combination with gemcitabine and cisplatin has shown promise as first-line therapy with category 1 evidence 1.
• In prostate cancer specifically, combination approaches appear more promising than nivolumab monotherapy:
  • Nivolumab plus ipilimumab showed better outcomes in patients with DNA-repair deficiency mutations compared to those without such mutations 2.
  • The PORTER trial evaluated various nivolumab-based combinations, with the most promising results seen when combining radiotherapy with CDX-301, poly-ICLC, and nivolumab 5.

Clinical Implications and Recommendations

• Patients with prostate cancer should be directed toward FDA-approved therapies with established efficacy rather than nivolumab monotherapy 1.
• For patients interested in immunotherapy approaches for prostate cancer:
  • Clinical trial enrollment should be considered as the preferred option 1.
  • Genetic testing for DNA repair deficiencies (particularly BRCA1/2 mutations) may help identify patients who might benefit from combination approaches that include nivolumab 2, 3.
  • Combination therapy approaches show more promise than nivolumab monotherapy for prostate cancer 6, 5, 2.

Potential Toxicities and Monitoring

• Immune checkpoint inhibitors like nivolumab can cause significant immune-related adverse events (irAEs) that require careful monitoring 4.
• In studies of nivolumab combinations for prostate cancer, common adverse events included:
  • Nausea, anemia, fatigue, and immune-related adverse events including adrenal insufficiency 3, 4.
  • Treatment discontinuation rates due to treatment-related adverse events ranged from 23.9% to 27.3% in the CheckMate 9KD trial 3.

In conclusion, while nivolumab has established efficacy in several cancer types, there is insufficient evidence to support its use as an effective treatment for prostate cancer outside of clinical trials or specific combination regimens, particularly in patients with DNA repair deficiencies.