Quality of Life in the Treatment of mHSPC: The STAMPEDE Trial - Hannah Rush
March 3, 2020
Arm C of STAMPEDE accrued between 2006 and 2013 and arm G accrued between 2011 and 2014. There was a period between November 15, 2011, and March 31, 2013, when both arms were accruing. This allows for a direct comparison of abiraterone + ADT with docetaxel + ADT in a cohort of patients that were randomized between the two therapies. Previously reported a comparison of these two groups demonstrated no difference in overall survival (Sydes et al), a finding which has been replicated in a separate meta-analysis (Wallis et al).
Making the decision between which of these two therapies to initiate treatment in a patient with newly diagnosed metastatic hormone-sensitive prostate cancer (mHSPC) may then be guided by other considerations. Dr. Hannah Rush presented a comparison of quality of life outcomes in patients enrolled in arms C and G of STAMPEDE during the period in which both arms were enrolling. She discusses the analysis and the findings in this conversation.
Hannah Rush, MBChB, Clinical Trials Unit, University College London, London, United Kingdom
Alicia Morgans, MD, MPH Associate Professor of Medicine in the Division of Hematology/Oncology at the Northwestern University Feinberg School of Medicine in Chicago, Illinois.
Alicia Morgans: Hi. I'm excited to have here with me today, Dr. Hannah Rush, who is a doctor in the Clinical Trials Unit at the University College of London. Thank you so much for being here.
Hannah Rush: Thank you for having me.
Alicia Morgans: Wonderful. So you presented a beautiful abstract at GU ASCO 2020, where you really talked to us about the quality of life outcomes that we had from patients receiving docetaxel or abiraterone in STAMPEDE. Can you tell us a little bit about STAMPEDE and the quality of life study that you did?
Hannah Rush: Of course. So I work as the doctor on the STAMPEDE trial, which is a multi-arm, multi-stage trial that opened in 2005 and has randomized patients to multiple different comparisons over the last 15 years. We initially started with five comparisons, which included a docetaxel arm, which was subsequently reported to significantly prolong overall survival. But the design of the STAMPEDE trial meant that as time went on, we are able to add in new comparisons. And whilst we were still recruiting to the docetaxel arm, we opened up an abiraterone comparison. And this meant we had a period where we were randomizing patients between treatment with docetaxel and abiraterone as well as some other treatments that were still open at the time and the standard of care arm.
So this gave us a really unique opportunity to compare outcomes in this patient cohort who have very similar characteristics. Obviously, they are just being randomized between the two arms and our first outcome was looking at overall survival. We subsequently reported that abiraterone also improved overall survival. And now I've used this opportunity to look at the quality of life in those patients who are randomized directly between the two treatments.
Alicia Morgans: Wonderful. So in this metastatic hormone-sensitive population, we have contemporaneously randomized patients to chemo hormonal therapy and abiraterone. How did you assess the quality of life in these arms in the study?
Hannah Rush: So we always planned to do a quality of life study and we used the EORTC QLQ-C30 questionnaire alongside the prostate cancer-specific module. So this meant we had an overview of how men were experiencing the general quality of life. The first questionnaire is about side effects related to the general symptoms of cancer. And then the second one is a little bit more specific about prostate cancer, although a lot of the symptoms that it talks about may be considered to be related to hormone therapy as well as early treatments. We decided that we'd like patients to repeat this quality of life questionnaire at multiple time points. So each followup appointment, they completed one of these questionnaires. This meant we had questionnaires six weekly in the first six months, then 12 weekly until two years. And then after that, they only did it six monthly. At this point in the trial, patients continue the quality of life questionnaires after progression, although we didn't chase them. So our data set post-progression is not as good as our data set pre-progression.
Alicia Morgans: Okay. So what did you find when you looked at the quality of life, both within each arm, the chemo hormonal arm and the abiraterone arm, and then the comparison between the arms?
Hannah Rush: So we decided to look at different aspects of the quality of life. So our main outcome was looking at the global quality of life, which is really the broadest overview of how men are feeling about their quality of life. It was just based on two questions. And from this analysis, we found that patients in both arms over time, their quality of life did slightly decrease compared to where they started. The abiraterone deterioration was sort of a slow, steady deterioration. But for patients treated with docetaxel, there was a sharper decline particularly in the first 18 weeks, which is the period of treatment with docetaxel.
What we were surprised to see was that it took a little longer for patients' quality of life to recover and catch up with those treated with abiraterone. And we had wondered whether in the second year when patients who were initially treated with docetaxel and now just on the hormone therapy alone, therefore having less ongoing treatments, whether their quality of life might overtake that of the patients on abiraterone. And we didn't see that, which was a little bit of a surprise.
Alicia Morgans: Wow. So when you think about these data, did you also assess things like pain?
Hannah Rush: Yes. So we tried to focus on things that we felt would really distinguish between the treatments. We looked at what are called functional domains, which is trying to establish how treatments are impacting on different aspects of a patient's life. So there are five key ones. Physical, which is checking if guys can sort of walk and do normal activities. There's role functioning, which is your ability to carry out your self-caring activities. And your social functioning, which is going out and spending time with your family. And we found all of those were superior for patients treated with abiraterone. The other two sort of functioning domains were cognitive and emotional domains, and those are exactly the same for both treatments.
Alicia Morgans: Very interesting.
Hannah Rush: And then you mentioned symptoms. We only looked at two in our analysis, which were pain and fatigue. We found that pain scores were higher for patients treated with docetaxel, indicating they had higher levels of pain. Also, fatigue scores were higher, but that did not reach the level of clinically meaningful difference for the fatigue scores.
Alicia Morgans: So how do you think about these findings in the context of your clinical practice?
Hannah Rush: That is a really interesting question. As I just alluded to at the end, we predetermined something called clinically meaningful difference and this was based on other research and quality of life work. In our primary outcome, the difference between the two arms over a whole two year period was just below the level we set to indicate the clinically meaningful difference. So I don't think it's a slam dunk that one is better than the other. However, I do think that there is a general pattern across many domains, including the global one, there's three functioning ones I mentioned and some of the symptoms. There seems to be a trend that generally patients treated with abiraterone reported better quality of life.
Alicia Morgans: Interesting. So when I think about this, I also always think that it's good to have a shared decision, but I'm in a situation in a medical system where I actually have access to abiraterone and docetaxel, as well as apalutamide and enzalutamide in the metastatic hormone-sensitive population where this work was done. You don't necessarily have that luxury at this point and to have those options, but it seems like an ideal opportunity. At least, I'd love to hear your thoughts on whether you think it's a reasonable opportunity to have a shared decision around all of the things that patients may experience, all the adverse events, all the quality of life data that you've now shared with us, and of course things like financial toxicity, to have a well-rounded discussion when you do have options in this clinical situation.
Hannah Rush: I think talking to our patients is the most important thing that we can do about with any treatment decision in any treatment setting. I think more data is useful as long as we can try and explain it in a clear way for our patients so they can weigh out the pros and cons. I was reading some really interesting research recently that was looking at men with earlier prostate cancer and they reported that they would trade about 6% maximum quantity of life for a better quality of life. So this is something that is really important for our patients to understand and be aware of. Although the difference did not exceed that clinically meaningful cutoff we made, I think it's still a big enough change that we should be talking about this with our patients.
Alicia Morgans: I absolutely agree. And I commend you and the team for analyzing this data, for thinking about it so carefully, and for sharing it with us. I sincerely look forward to the paper as well and to having these conversations with my patients in the clinic. Thank you.
Hannah Rush: Thank you very much.