Metastatic Hormone-Sensitive Prostate Cancer Progression to CRPC - Episode 2
Jorge Garcia, MD:So this is a patient who actually is presenting in an unusual manner for us in the United States. This patient has what we call de novo metastatic disease. Over the past 4 years, a lot of changes have occurred in the management of these men with advanced disease. I think, perhaps, the most important thing is how the patient walks into the office. We now consider patients by volume. Although there are many definitions for volume, truly the definition for volume means how many lesions they have and where those lesions are located. So he has what we call, based upon the American dataand for that matter, the French data, which are what we use to define volume of disease—high-volume metastatic disease.
I think the complexity of deciding between chemotherapy and an oral agent in the context of de novo presentation is controversial, in the sense that there are no head-to-head data thus far. We have pieces of data that would suggest that both agents, based upon his high-volume disease, could actually be applicable in this case. We have the American data that look specifically at patients with de novo metastatic disease, where we actually added docetaxel-based chemotherapy to the backbone of suppression of testosterone with ADT [androgen deprivation therapy]. And clearly, that data demonstrated a significant survival improvement for men with high-volume metastasesalmost a 40% risk reduction of mortality for those men who received chemotherapy in addition to suppression of testosterone.
We also have the British data that actually supported that approach. And then, more recently, a couple of years ago we had the French data, or the so-called LATITUDE trial that demonstrated that the addition of abiraterone acetate, which is an oral agent that is capable of blocking specific enzymes within the adrenal glandspecifically the CYP17 enzyme and other enzymes, such as 17,20-liase or hydroxylases, which are enzymes that allow mediation of early androgen production in the adrenal gland. The addition of abiraterone to ADT in that data also demonstrates a significant survival improvement, specifically for patients with high-volume disease.
So in my mind, if you define the volume, the standard of care right nowat least in my mind—in the United States, for high-volume disease you should give either suppression of testosterone plus docetaxel-based chemotherapy at 6 cycles or can consider giving suppression of testosterone plus abiraterone acetate on a continuous basis until either progression or the development of drug intolerance.
I think the bigger question resides right now for patients who don’t have high-volume disease, for which chemotherapy is not the standard, in my opinion. However, the British, also with the so-called STAMPEDE trial, have helped us pave the treatment options for these patients. In my mind, with the best data that we have, I do believe men with de novo low-volume disease should not be offered chemotherapy but rather should be a counseled to receive the addition of abiraterone on top of their suppression of testosterone.
So I think the response isit depends how you defineresponse, obviously, in the way that I think of these agents and the goals of the care for these patients. The No 1 priority for me, when looking at the data, is survival benefit. I can tell a patient with de novo disease, if we’re going to put them on abiraterone in the context of high-volume disease, that I can put them on ADT and abiraterone and can reduce their risk of mortality by almost 40%, which is the hazard ratio of reduction in mortality, which is what we saw in that LATITUDE data.
I can also tell the patients that the likelihood of serological response, which is the ability of this treatment to lower their PSA [prostate-specific antigen], is significant as well. We also know that the lower the PSA, the better patients do. So the nadir PSAwhich is, what is the lowest PSA that you achieve on therapy, within 6 months for that man and also at 12 months—is a very strong predictor of outcome for these patients.
Lastly, another important topic of how one defines efficacy would be how long it will take the disease, on treatment, to progress. And that progression, again, is defined by a rising of your PSA despite treatment, meaning despite the lack of testosterone, or symptomatic progression, or radiographic progression. That is the time that it takes this man to develop castration-resistant prostate cancer. So I would argue for survival, delaying progression, and serologically decreasing your PSA.
Transcript edited for clarity.
Case: Met HSPCa Progressing to mCRPC
Pt was started on ADT with LHRH agonist-based therapy and abiraterone + prednisone. He also was placed on monthly zoledronic acid.
Patients is started on Docetaxel-based chemotherapy (75mg/m2 on 21-day cycles)
Patient completes 6 cycles of therapy with expected AEs including G1 fatigue, G1 alopecia and G1 peripheral neuropathy. His scans at the completion of chemotherapy showed SD with tumor burden reduction in liver lesions and SD in bones. His Hemoglobin level at the completion of chemotherapy is 12.1 g/dL and his ANC and platelets are also within normal limits.