Despite tremendous progress in our understanding of prostate cancer and significant expansion in the therapeutic landscape, prostate cancer continues to represent the most common cancer in men. Metastatic castration-sensitive prostate cancer (mCSPC) is hormone-sensitive prostate cancer that has spread outside of the prostate but continues to respond to androgen deprivation therapy (ADT). This form of prostate cancer remains incurable, pointing to the unmet need for new therapeutic options. I look forward to joining colleagues later this week for the annual American Society of Clinical Oncology Genitourinary Cancer Symposium (ASCO GU) to share new knowledge in the prostate cancer space as we work together to find ways to improve quality of life for patients with prostate cancer and eliminate the disease.
The value and limitations of ADT
While ADT endures as the treatment backbone for mCSPC, newer androgen receptor inhibitors (ARIs) are addressing the specific limitations of ADT – namely, the adaptive mechanisms that ADT initiates in patients’ cancer cells that eventually render the therapy useless in the patients who were once responsive to it. These newer ARIs have offered ways to combat the influence of androgens once the cancer becomes resistant to ADT.
Unfortunately, therapies added to ADT have failed to cure mCSPC, leaving us to continue our search for more effective ways to tackle the disease. This search seems to be leading us to a paradigm shift in terms of when to deploy the tools in our toolbox. Specifically, the value of turning to other treatments to help fill the void once patients stop responding to ADT is becoming overshadowed by evidence for the benefits of combining ADT with other agents as early as possible.
Moving beyond ADT as the standard of care
The approach for mCSPC treatment has understandably involved trying therapies in sequence. Indeed, it is appealing to limit side effects to those associated with one drug at a time and to begin with ADT because of its high initial response rates. It is also comforting to know there are more options available in the future if the current treatment strategy stops working.
What we are learning, however, is that combining ARIs with ADT can prolong both overall survival and progression free survival while maintaining quality of life. In other words, even those with low volume disease can benefit more from early combination therapies than from sequential treatment strategies. Though the use of ARIs in combination with ADT is not devoid of unwanted side effects, these side effects are not associated with higher mortality risk across the mCSPC population.
Going forward: Customizing treatment for each patient with mCSPC
We have long known that the way to effectively treat patients with mCSPC involves preventing the problematic effects of hormones. The story that is emerging from the research is that we may be more successful in fighting mCSPC if we attack the action of androgens through multiple mechanisms as early as possible rather than allowing the cancer to adapt to our therapeutics before we introduce new ones. At Janssen, we are actively incorporating these new insights into our discovery process as we urgently seek a cure for mCSPC.
Though the evidence points to the value of earlier, more aggressive intervention in mCSPC as a means for obtaining more profound treatment responses and preventing delays in receiving effective therapies, there is still no one-size-fits all solution for mCSPC. For instance, combination therapy may lead to intolerable side effects in certain patients and therefore not be the best approach for them. Until we have a reliable cure for the disease, each patient’s condition and preferences should continue to drive mCSPC treatment recommendations.
To learn more, visit www.janssen.com/ascogu2021
