Now that we have new treatments available to fight advanced, metastatic prostate cancer we need ways to decide on the best treatments given that many of the treatments occupy the same disease space. This is especially important with the soaring costs of many treatments as well as the need to not waste time by giving a treatment that will not work, thus delaying using a more effective treatment.
We know that not all men will get any benefit (respond) to all the available treatments, so how can we predetermine who will respond to a drug and who will not. Answering this type of question is as vital as our continuing the development of additional new treatments. In reality as we do develop additional treatments this issue becomes increasing more important.
In pursuit of trying to develop ways to pre-determine drug sensitivity, at the most recent American Association of Clinical Oncologists (ASCO) Annual meeting Dr. Emmanuel Antionarakis, MD, Johns Hopkins Sidney Kimmel Comprehensive Cancer Center in Baltimore formally presented data showing that a simple blood test maybe able to identify men who will not be responders to enzalutamide (Xtandi). He found that the presence of a splice variant androgen receptor (AR) V7 in circulating tumor cells signaled a person who would not respond to enzalutamide (see my blog post at: http://advancedprostatecancer.net/?p=4490). Given that it is highly likely that enzalutamide will soon be approved in the pre-chemotherapy space, joining sipuleucel-T (Provenge) and abiraterone (Zytiga), this information becomes even more important.
Even though we have these new treatments, docetaxel (DTX) remains the first-line chemotherapy for castration-resistant prostate cancer (CRPC). Like the other newer drugs not all men are responders with non-responders possibly being as high as 50%. Even the non-responders to docetaxel pay the price of the drugs significant toxicity.
Therefore, like the other new drugs there is a need for new biomarkers to identify responders to chemotherapy.
A study presented at ASCO GU evaluated the ability of circulating microRNAs to predict chemotherapy outcomes in men with castrate resistant prostate cancer (CRPC).
The researchers performedglobal microRNA profiling on chemotherapy resistant and sensitive cell lines to identify candidate circulating microRNA biomarkers.
They found that eighteen microRNAs were associated with PSA response or overall survival (p<0.05). Chemotherapy non-responders and men with shorter survival had high pre-chemotherapy levels of other microRNAs.)
The researchers determined that these microRNAs were independent predictors of overall survival when modeled with hemoglobin levels (HR 2.6, 95%CI 1.4-5.1; p=0.02), PSA response (HR 2.1, 95%CI 1.1-3.9; p=0.03), and visceral metastases (HR 2.0, 95%CI 1.1-3.5; p=0.03).
They concluded that circulating microRNAs are potential early predictors of docetaxel chemotherapy outcome and may be useful in stratifying men in future clinical trials as well as pre-determining who would benefit from chemotherapy with docetaxel.
Both Dr. Antonarakis and Dr. Horvath’s studies need to be replicated. Hopefully they both will be quickly replicated so their findings can be quickly be placed in to the standard of care. This would improve both our health and save money.
J Clin Oncol 32, 2014 (suppl 4; abstr 44); Lisa Horvath, Hui-Ming Lin, Lesley Castillo, Kate Lynette Mahon, Karen Chiam, Brian Yong Lee, Quoc Nguyen, Wenjia Qu, Michael J. Boyer, Martin R. Stockler, Nick Pavlakis, Gavin M. Marx, Girish Mallesara Hiriyanna Gowda, Howard Gurney, Susan J. Clark, Alex Swarbrick, Roger J. Daly; Chris O’Brien
Joel T Nowak, M.A., M.S.W.