Beginning with the data from TAX-327 demonstrating the overall survival advantage of docetaxel in men with metastatic castration-resistant prostate cancer (mCRPC), this disease space has gone from one of the repeated dead-ends to a flourishing research field with many agents gaining approval over the last 15 years as a result of demonstrated survival benefits.
Following the introduction of docetaxel for mCRPC, the IMPACT and TROPIC trials demonstrated a role for sipuleucel-T and cabazitaxel in mCRPC. The AFFIRM and COU-301 trials demonstrated the benefit of second line enzalutamide and abiraterone, respectively, following chemotherapy. Subsequently, PREVAIL and COU-302 demonstrated survival benefits to these agents in the first line setting. More recently, there have been substantial advances in the second and third line treatment space including ALSYMPCA (of radium-223), CARD (of cabazitaxel versus enzalutamide/abiraterone switch), PROfound (of olaparib versus enzalutamide/abiraterone switch), TRITON2 (of rucaparib), and many other ongoing trials.
However, to have tangible benefits for patients, we must be able to translate these findings in clinical trials to routine, real-world patient care. There are therefore two main issues to address: first, in routine practice, are patients receiving treatment with approved agents and, second, how do the outcomes of patients treated with these agents in routine practice compared to those treated within the trials.
Addressing the first of these, we assessed the utilization of life prolonging agents among patients with mCRPC in Ontario, Canada. To be included, patients had to receive at least one life prolonging therapy. Thus, we cannot assess the proportion who never received any prostate cancer directed therapy with proven survival benefit. However, we are able to assess treatment patterns and utilization of subsequent lines of therapy. As is probably expected for most clinicians treating mCRPC, abiraterone acetate and enzalutamide were the most commonly used treatment approaches in the first line space.
More interestingly, we found that while all patients in this cohort (based on the inclusion criteria) received one line of life prolonging therapy for mCRPC, only a small minority received further lines of care: 16%, 8%, and 3% of patients received 2, 3, or 4 or more lines of therapy. Thus, more than 7 in 10 patients only received one life prolonging treatment regime. This is notable as much of the recent research has focused on optimizing second, third, or fourth-line treatment. However, we found that most patients never received these lines of treatment. Further, we restricted to patients who died during observation who, given their diagnosis of mCRPC most likely died of prostate cancer, the proportion was very similar.
Addressing the second main question, there is a well-established efficacy-effectiveness gap in which real world effectiveness of therapy is substantially lower than would be anticipated based on RCT data. Indeed, our data supported this with a median overall survival of approximately 19 months, which is substantially lower than what has been reported in clinical trials. This may be driven by differences in patient characteristics included on trials compared to real-life practice, differences in the use of subsequent lines of therapy, or other factors.
Taken together, these data highlight the importance of efforts to disseminate proven life-prolonging treatments to the prostate cancer community. While clinical trials provide critical information assessing the efficacy of new treatment paradigms, our patients can only realize the benefits of these approaches when they are widely disseminated. Thus, ongoing efforts to understand real world treatment patterns and outcomes is critical to improving prostate cancer outcomes for patients.
Written by: Christopher Wallis, MD, PhD, FRCSC, Assistant Professor, Division of Urology, University of Toronto
Read the Abstract