THE "NEW" PROSTATE CANCER INFOLINK

An article in the April issue of Lancet Oncology has provided additional data from the randomized, double-blind Phase III PREVAIL trial of enzalutamide versus placebo in men with asymptomatic and minimally symptomatic, chemotherapy-naive patients with metastatic castration-resistant prostate cancer (mCRPC).

Specifically, Loriot et al. have provided prospectively collected data indicating that patients treated with enzalutamide as opposed to placebo in this trial not only gained from a median survival benefit of > 5 months, they also gained from better physical functioning and other improvements in overall quality of life. This was also the case in the earlier Phase III trial of abiraterone acetate + prednisone vs. placebo + prednisone in an analogous group of patients.

We should be clear that these were not vast improvements — but they were significant. And for patients with mCRPC things like delays in onset of bone pain, avoidance of clinically evident (symptomatic) skeletal-related events, and other evidence of deferral of signs and symptoms of progressive disease are important.

Perhaps just as important as these findings, however, are the editorial comments in Lancet Oncology by Dr. Ethan  Basch about the implications of such findings from these large, randomized trials. Historically, the critical factor in seeking approval of most new drugs in the treatment of late-stage prostate cancer has been a survival benefit compared to the current standard of care. Some time ago Dr. Basch started to argue that trials of this type — with a primary endpoint of improved overall survival — should also be designed to include secondary endpoints focused on outcomes that were demonstrative of improved quality of life. Dr. Basch’s premise was that, quite apart from the improved survival benefit, which is often relatively small, patients and their physicians would also benefit from knowing that treatment of late-stage prostate cancer could also be expected to come with quality of life benefits as well.

The data from recent trials of abiraterone acetate, enzalutamide, and radium-223 have all shown both survival benefits and such improvements in quality of life. Nearly 2 years ago, the Prostate Cancer Roundtable also made this concept a core element of its national policy agenda, stating that:

We encourage the inclusion of quality-of-life-related endpoints, based on patient-reported outcomes data, in pivotal trials of all biologic and pharmaceutical agents being assessed for regulatory approval in the treatment of prostate cancer with a primary endpoint of improved survival — such that quality-of-life-related data (positive or negative) and survival data can be included in labeling for products indicated for treatment of prostate cancer when appropriate.

In his comments on the article by Loriot et al. in Lancet Oncology, Basch now writes that:

Patient-reported outcomes have now become a standard part of clinical research in metastatic castration-resistant prostate cancer. Omission of these outcomes in any product development program for this type of cancer must be considered as an incomplete evaluation of clinical benefits — and developers could find their product regarded unfavorably by regulators, guideline developers, and payers if such information is unavailable.

Unfortunately the full text of Basch’s comments is not available on line (and we thank Dr. Basch for providing us with the complete text of his remarks). However, we can assure readers that Prostate Cancer International and The “New” Prostate Cancer InfoLink are in complete agreement with Dr. Basch’s perspective. While we continue to seek treatments that can radically reduce the risk of disease progression and prostate cancer-specific mortality for men with progressive, metastatic prostate cancer, it is imperative that new treatments demonstrate not just a few months of extended survival but also clear evidence of retention of good quality of life while that life is being extended. And this is not a mindset that should be limited to prostate cancer; it applies today to trials of new drugs for many other forms of cancer too.

Filed under: Drugs in development, Living with Prostate Cancer, Management, Treatment | Tagged: evidence, quality of life, survival, trials |