Patient-reported outcomes and prostate cancer drug development


There is an excellent opinion piece in this this week’s New England Journal of Medicine that addresses the need for greater focus on patient-reported outcomes in the development of drugs for the treatment of cancer.

This is by no means the first time that the author (Dr. Ethan Basch) has let his views be known on this topic. However, this article is perhaps one of the more public and cogent explanations he has given of why we need to (and how we can) do much better in ensuring that patient-reported outcomes are a key element of the data package that is created to support approval of drugs for the treatment of cancer.

As most regular readers of this blog will be aware, the focus for drug developers in seeking U.S. approval of new agents for the treatment of cancer is survival. Does the new drug extend life by comparison with available therapies? And if it does improve survival, does it do this with an acceptable risk for side effects of clinical importance?

However, as Dr. Basch carefully points out in his article, a key issue for the patient is often, “How will this drug make me feel while I am taking it?” The additional few months of a survival than a new drug may offer has to be weighed against the patient’s quality of life. And, by comparison to the quantity of their life, some patients may place greater value on the quality of their lives than others.

Dr. Basch mentions the fact that abiraterone acetate (Zytiga) is one of the very few cancer agents approved in recent years that explicitly includes information of this type in its prescribing information. In developing this drug, the original developer, Cougar Pharmaceuticals, specifically set out to measure the time to use of opioids for pain management among patients with chemotherapy-naive, metastatic, castration-resistant prostate cancer (mCRPC) with minimal baseline symptoms of pain at the start of the trial. They were clearly able to show that abiraterone acetate extended this time period, and the prescribing information for abiraterone acetate, when referring to its use in treatment of men with chemotherapy-naive mCRPC, reads as follows:

The median time to opiate use for prostate cancer pain was not reached for patients receiving ZYTIGA® and was 23.7 months for patients receiving placebo (HR=0.686; 95% CI: [0.566, 0.833], p = 0.0001). The time to opiate use result was supported by a delay in patient reported pain progression favoring the ZYTIGA® arm.

This is an outcome based primarily on patient-reported outcomes of treatment (together with actual physician prescription of opioid therapy to manage the symptoms of increasing pain).

However, there are a lot of other potential patient-reported outcomes affecting quality of life that could be assessed in the development of selected drugs for the treatment of prostate cancer, and many of these so-called PROs would not be that difficult to assess in appropriate randomized clinical trials. They include things like the following:

  • Satisfaction with and effects on erectile function
  • Degree of impact of hot flashes and impact on quality of life
  • Degree of impact on symptoms such as tiredness or sleep disturbance (identified by Dr. Basch in his article)
  • Effects on cognitive ability

As Dr. Barsch further notes, the U.S. Food and Drug Administration has, over the past 5 years or so, shown a much greater desire and willingness to include data on such secondary endpoints in the product labeling for new drugs. However, a key issue for the patient advocacy community will be to push drug developers and their partners in the clinical research community to include the collection of data related to such endpoints in their clinical development protocols. There is an important role here for patient advocates in their interactions with  such organizations as the FDA, the Patient-Centered Outcomes Research Institute (PCORI), drug developers, the National Cancer Institute, and the major clinical trials consortia such as the Southwest Oncology Group (SWOG).

By the end of 2015, the “New” Prostate Cancer InfoLink would like to see every new, pivotal, randomized, well-controlled Phase III clinical trial that is designed to support approval of a new drug for the treatment of prostate cancer include data collection to address at least one well-designed primary or secondary endpoint that is based on patient-reported outcomes data, so that we can clearly establish that such new drugs address patient-defined needs in addition to simple survival. That is clearly an optimistic goal … but if you don’t start to ask, you don’t start to get!

7 Responses

  1. Hear, hear!

  2. It is also a concern with who treats you. I recently switched oncologists and the difference is startling. My new oncologist recognizes that my treatment may affect me and he discusses it with me. My previous oncologist (top doctor at a major New York City cancer center) just did not care and did not want to hear about it.

    The take away is: do not hesitate to change if your doctor will not listen to you (no matter who is thinks he is).

    Bill Manning

  3. Agree on both respects, the information shouldbe included and your doctor should be more humane, if not human!

  4. Yes. … What is the point in living a few more months, if the QOL is not good.

    Ironically, I went through 6 months of abiraterone with almost no side-effects — but my PSA soared to 500+. I have now been on enzalutemide for 6 months; my PSA is down to a steady 140/150, but the side effects are pretty grim.

    Hobson’s choice! … My doctor is thinking about a PARP next! I wonder what side effects that will bring.

  5. I honestly say that at SWOG the patient experience is discussed with each trial as they are reviewed monthly. But that is not what you are requesting and I as the patient advocate in the GU Committee will indeed express the points made here as necessary for each new trial. It’s also not impossible to go back and get some of this data, but we have a pretty good eye on the ball with patient experiences.

    Thanks for this post.

  6. Dear Tony:

    For data to appear in any product’s prescribing information, collection, review, and formal approval of those data must be built into the original trial protocol that gets approved by the FDA. Retrospective analyses (“data mining”) can always be carried out, but — unless it is negative data that shows increased risk that was not available at the time of the original approval — it will never become data that is part of the FDA-approved information about the drug, and so the companies cannot communicate such data directly to physicians and patients.

  7. New to the club. Third week on Xtandi after Jevtana lost its effect. Some really good and really bad days. Now “averaging” out as strong mornings until 2-ish then fatigue and appetite (loss of) make interaction and writing hard. Stiffness and dragging legs slightly improved for the m of the mCRPC but shifting to mild pain opiates is a concern for driving, an essential QOL for me.

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