For some patients with advanced prostate cancer who have experienced various treatment options and have not responded, it may be possible to try treatment with the PD-1 inhibitor, pembrolizumab. The latest research evidence suggests that pembrolizumab may be effective in some patients with advanced prostate cancer. Now, UK researchers have set out to study how to screen out this group of patients.
While PD-1 and PD-L1 inhibitors have been shown to work in a variety of cancers, they have been generally effective in prostate cancer.
The latest study (KEYNOTE-199), presented by Professor Johann De Bono of the Royal Marsden Hospital in London at the American Society of Clinical Oncology (ASCO) 2018, showed 11% of 258 patients with metastatic castration resistant prostate cancer (mCRPC) showed efficacy after one year of pembrolizumab immunotherapy, even in some patients who did not express PD-L1.
He believes that genetic biomarkers may help determine which prostate cancer patients don’t respond to immunotherapy.
KEYNOTE-199 study
The KEYNOTE-199 study included 258 patients, all of whom met the following criteria:
- metastatic debulking-resistant prostate cancer;
- received more than 1 endocrine regimen, or 1 to 2 chemotherapy regimens (including docetaxel);
- ECOG score of 0 to 2.
There are three patient groups of focus in this study:
- Group 1: a total of 131 individuals, all PD-L1 positive (measurable lesions);
- Group 2: 67 total, all PD-L1-negative (measurable lesions);
- Group 3: 60 total, all PD-L1-negative (measurable lesions);
- Group 3: 60 total, all with bone metastases and PD-L1 negative (non-measurable lesions).
All three groups of patients were treated with pembrolizumab 200 mg for 35 weeks. Patients were imaged every 9 weeks during the first year of follow-up and every 12 weeks after one year.
Follow-up showed that in groups 1 and 2, where lesions could be evaluated, a total of 10% of patients had a reduction of more than 30% in their original lesions. Prostate specific antigen (PSA) levels decreased by more than 50% in 11% of patients in all 3 groups.
Notably, some of the patients with PD-L1-negative disease were included in the patients who were treated with pembrolizumab, either with tumor shrinkage or with a decrease in PSA.
A pooled analysis of the patients with the best outcomes in this study found:
- In group 1, 2% of patients had complete remission, 4% had partial remission, 17% had stable disease, and 4% had stable disease lasting more than 6 months.
- In Group 2, 3% of patients had partial remission, 21% had stable disease, and about 3% had stable disease for more than 6 months.
- In group 3, no patients had an effective response to treatment.
A statistical analysis showed that a total of 11% of patients in all 3 groups remained stable for more than 6 months, including those who achieved complete or partial remission.
The above results suggest that a small proportion of prostate cancer patients could benefit from treatment with pembrolizumab.
Interestingly, genomic analysis of those with effective pembrolizumab showed that these patients had some genetic mutations associated with response, such as mutations in the BRCA2 gene.
In fact, researchers found that patients with mutations in BRCA1/2 or ATM achieved stable control in 22% of cases.
In addition, across the trial group, 59% of patients experienced treatment-related adverse events, and 14% had serious adverse events. The most common adverse events were fatigue and diarrhea, while immune-related adverse events included hyperthyroidism and hypothyroidism.
Summary
- The 2018 National Comprehensive Cancer Network (NCCN) updated guidelines have recommended pembrolumab for the treatment of metastatic debulking-resistant prostate cancer, but only as a follow-up systemic therapy for patients who have experienced disease after receiving at least one systemic therapy (eg, docetaxel). patients who have progressed.
- Immunotherapy has been shown to be a more precise and gentle anti-cancer therapy, but it is still only available for a small number of patients. The clinical challenge is to accurately assess whether patients will benefit from it and how to make immunotherapy work in more patients.