A study published in the Journal of Clinical Investigation suggests stratification within the patient population of advanced prostate cancer.
The report indicates that a subset of 8% of patients have deficiencies in a key DNA repair process called mismatch-repair. This results in worse overall survival for this group. Crucially however, these patients also show enrichment for the marker PD-L1, opening up therapeutic options for these patients.
This molecule (and the PD-1 receptor it binds to) are targeted by several new checkpoint inhibitor drugs which have gained Marketing Authorisation in recent years, including Bristol-Myers Squibb’s Opdivo (Nivolumab), Merck’s Keytruda (Pembrolizumab), and Merck, Pfizer, and Eli Lily’s Bavencio (Avelumab).
This leaves open the potential of checkpoint inhibitors being repurposed for this subset of patients, opening up a new potential indication for these drugs.
The work was a collaboration between the Institute of Cancer Research (ICR) in London, and the Dana-Farber Cancer Institute in Boston. Professor Paul Workman, Chief Executive ICR said:
“We are seeing a revolution in cancer treatment as immunotherapy becomes an important option for many types of the disease.
“Immunotherapy is an unusual treatment in working best in cancers that have a lot of mutations. Prostate cancers normally tend to have fewer mutations than other cancer types, which may be why immunotherapy has so far only been successful in a small minority of patients.
“This new study is exciting in providing a way to pick out those men with prostate cancer who have the most aggressive, unstable disease and the worst survival – but who conversely might be the best responders to immunotherapy.”