Christopher Wallis: Hello, and thank you for joining us for UroToday journal club. Today we’re discussing a recently published paper examining treatment patterns and outcomes in patients with metastatic castrate-resistant prostate cancer in a real-world practice setting in the United States. I’m Chris Wallis, a fellow in urological oncology at Vanderbuilt. With me today is Zach Klaassen, an assistant professor in the division of urology at the medical college of Georgia. This is the citation recently published in Clinical Genitourinary Cancer and led by Dr. Daniel George.
The field of metastatic castrate resistant prostate cancer has evolved rapidly over the last 10 or 15 years. Prior to 2004, there were no approved therapies with life-prolonging benefits. Since that time there’ve been a proliferation of treatment approaches driven by clinical trials. However, the utilization of these in clinical practices, relatively unclear. AUA, ASTRO, and SUO guidelines provide a number of recommendations, primarily highlighting, as you can see in the first line here, the [inaudible 00:01:09] should offer ADT along with another therapy for patients who are newly diagnosed with metastatic castrate resistant prostate cancer. These additional therapies could include abiraterone, docetaxel or enzalutamide, and there’s actually new data coming out that will further expand this list.
Again, we see in a slightly different presentation this time adopted from Dr. Bertles work at ESMO, that there are a variety of treatment approaches, many in each of the first and second line settings. And thus it is relatively unclear how we should utilize these treatments and certainly identifying existing practice patterns is helpful to guide that. To that end the authors undertook an investigation of real-world treatment patterns in health outcomes in patients with advanced metastatic castrate resistant prostate cancer. And to do so they use the Flatiron Health Database, which is an agglomeration of electronic health records data capturing more than 280 cancer clinics, and more than 2 million patients with cancer. And within the EHR data, the authors utilize the CRPC definition, comprising a PSA measured at the start of formalin therapy, increased PSA greater than two nanograms per milliliter, over baseline, and a follow-up PSA measurement, which was higher than that one within three months. Utilizing this definition, the authors identified 4,187 patients with prostate cancer of whom 4,000 had metastatic disease and just over 2,500 had metastatic CRPC. And these patients were predominantly treated at community centers, had a median age of 74 years, that were predominantly white, had a medium PSA of 22, and about 40% had stage four disease at diagnosis, and over half of these, this was unknown. At this point, I’ll pass it over to Dr. Klaassen to talk through the results of this study, as well as implications of the findings.
Zachary Klaassen: Thanks Chris. So we can see that in this trial of the Flatiron Health Database, 77% of patients receive first-line life-prolonging therapies. Among these patients that receive first-line therapies 49% of then went on to receive second line therapy, and among these patients 43% went on to see third line therapy. These therapies, as Chris mentioned, included abiraterone, enzalutamide, docetaxel, cabazitaxel, and sipuleucel. So in the first line of treatment, you can see here that 65% of patients received abiraterone or enzalutamide, whereas only 7% of patients received combination therapy. Moving to the second line, you can see that 54% of patients then received enzalutamide or abiraterone, and then improvement in the utilization of combination therapy to 17%. In the third line treatment, you can see that the predominant medication use was docetaxel, and we do see an improvement to 18% of patients receiving combination therapy.
So you can see here in this table, the duration of metastatic castrate resistant prostate cancer treatment by line of therapy delineated by first, second, and third line is displayed here with the treatment on the left. And in the first-line therapy, the longest duration of treatment was seen in radium-223 at six months with the combination therapy of 7.3 months, max. And in the second line, you can also see that the most common treatment was abiraterone and enzalutamide, but the longest duration of treatment was also seen in radium-223 overall of five months, and the combination therapy of 5.2 months. And the third line, the longest duration of treatment, once again, was radium-223 at 4.4 months overall with single agent 5.1 months.
So this is a Sankey diagram looking at treatment sequencing. You can see here that the first-line treatment, as we’ve mentioned, was most commonly second generation engine and receptor access targeted therapy. When we look at the treatment sequencing a little bit further in the second line, the most common switch was from advanced androgen receptor therapy to the other androgen receptor therapy that did not received previously. So if they received enzalutamide upfront, they come and they went to abiraterone and vice versa if they received abiraterone upfront, they subsequently went to enzalutamide. In terms of the second most common second line treatment pattern was from docetaxel to enzalutamide. In the third line treatment. We see that most commonly patients went from abiraterone to enzalutamide, and second most common and most from enzalutamide to docetaxel, and third most common was from docetaxel to cabazitaxel.
Looking specifically at the radium-223 utilization, it was quite low. Actually, if you look at the first line, it was 2% of patients, second line 3% of patients, and third line 8% of patients. Looking at combination rate regimens compared specifically to radium-223, and the first line was 7%. And the second line was 17%, and in the third line was 18%. This is a capital marker of looking at overall survival of all patients in this study with metastatic castrate resistant prostate cancer. You can see here that the median overall survival was 21.2 months with a 95% confidence interval of 19.6 to 22.5 months.
So several discussion points from this flat out and analysis of treatment patterns for men with metastatic castrate resistant prostate cancer and this study showed that only 77% of metastatic castrate resistant prostate cancer patients received a life prolonged therapy with about 50% of these patients receiving a subsequent life prolonged therapy. The most common therapies per line were abiraterone and prednisone in the first line. In the second line enzalutamide, and in the third line, docetaxel. Interestingly and important to point out is that the common practice of back-to-back use of abiraterone and prednisone and enzalutamide are a deviation from guidelines, given the lack of evidence. So we commonly will give patients either abiraterone or enzalutamide in the first line, and then subsequently in the second line, when they progressed, we switched this to treatment to the other anti-androgen therapy that they did not have. And there’s very little evidence to justify this. So this study does highlight at that utilization pattern.
Radium-223 was likely under utilized in this cohort. Approximately two to 4% of patients received radium two to three, subsequent to taxanes, or second-generation androgen access therapy. It was prescribed both as monotherapy and in combination therapy. However, the utilization did increase in the second and third line settings. In this study, the overall survival for patients was less than two years from diagnosis of metastatic castrate resistant disease, which is lower than the overall survival in phase three trials of chemotherapy naive patients, which was roughly 32 to 34 months. And this likely reflects the real world setting of this study were likely patients with poor performance status in the community where included in the study, whereas these patients are often excluded from randomized controlled trials.
So in conclusion, among more than 2,500 patients with metastatic castrate resistant prostate cancer in a real world setting, there was an under utilization of life prolonged treatment, and this data may inform future clinical trial design, as well as highlight the need for here in the treatment guidelines and to inform clinical decision-making. We hope you enjoyed this UroToday journal club, and thank you for your attention.