But there may be reason to anticipate that immunotherapies will prove important in prostate cancer treatment. Studying the few patients who do seem to benefit from prostate cancer immunotherapies might be one way to find new paths forward. Anecdotal reports suggest that some patients may “respond exquisitely” to these therapies, Dr Pal noted.

As an example, he pointed to recent work on the PD-1 inhibitor pembrolizumab (Keytruda) by researchers at the Oregon Health & Sciences University (OHSU)’s Knight Cancer Institute in Portland and Johns Hopkins University’s Sidney Kimmel Comprehensive Cancer Center in Baltimore, Maryland.3 These researchers found that among patients whose prostate cancer had proven resistant or refractory to the androgen receptor antagonist enzalutamide, pembrolizumab showed “dramatic” PSA responses in several patients.


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Other researchers have already gone back to the drawing board to design combinations of immunotherapies, both with other immunotherapies and with traditional cancer treatment modalities like chemotherapy and radiotherapy.

A prostate tumor’s low mutational burden, for example, might make cancers cells more difficult for immune T cells to recognize; combining immune checkpoint blockade with cancer vaccines, however, might be able to overcome that challenge.4 Ipilimumab is also being investigated in combination with the GVAX-PCa and PSA-TRICOM investigational cancer vaccines with promising early results.

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But early results for immunotherapy monotherapies seemed promising as well. Whether new combinatorial approaches can salvage immunotherapy for prostate cancer, or will just grow the list its failures against these tumors, remains to be seen.

References

  1. Rekoske BT, McNeel DG. Immunotherapy for prostate cancer: false promises or true hope? Cancer. 2016 Sep 20. doi: 10.1002/cncr.30250 [Epub ahead of print]
  2. Cordes LM, Gulley JL, Maden RA. The evolving role of immunotherapy in prostate cancer. Curr Opin Oncol. 2016;28:232-40. doi :10.1097/CCO.0000000000000281.
  3. Graff JN, Alumkal JJ, Drake CG, et al. Early evidence of anti-PD-1 activity in enzalutamide-resistant prostate cancer. Oncotarget. 2016 Jul 12. doi: 10.18632/Oncotarget.10547 [Epub ahead of print]
  4. Rekoske BT, Olson BM, McNeel DG. Anti-tumor vaccination of prostate cancer patients elicits PD-1/PD-L1 regulated antigen-specific immune responses. Oncoimmunology. 2016;5(6):e1165377. doi: 10.1080/2162402X.2016.1165377