Based on the controversial nature of the SWOG 9346 findings, presented at the 2012 Annual Meeting Plenary Session, ASCO intiated a pilot program at the meeting for a “town hall” type of discussion, where attendees could voice their concerns and questions, and where presenter Maha Hussain, MD, University of Michigan Comprehensive Cancer Center, Ann Arbor, and discussant William K. Oh, MD, Mount Sinai School of Medicine, New York, could respond.
At the post-plenary discussion, Dr. Hussain recapped the results of the study and acknowledged that the study was not designed to look at extensive vs minimal disease prospectively.
“I was surprised at the data. Intermittent androgen deprivation is thought to be most appropriate in patients with less metastatic disease burden, yet our results based on the secondary analysis suggest that intermittent therapy was especially inferior in the minimal disease group of patients. However, based on the primary results of the study, continuous therapy is the continued standard. Patients choosing intermittent therapy should be counseled regarding the data from this trial and the risks vs benefits of treatment,” she noted.
‘Difficult to Interpret’
Dr. Oh said, “These results are difficult to interpret. We want the best for our patients. These data from a large, well-powered, randomized controlled trial are not what we expected. But there is a risk of looking for information in a subset analysis. That guidance would be wrong.”
That being said, he called these results “important,” and added, “It is clinically relevant if an option is up to 20% worse [in overall survival]. We want to balance quality of life with the primary objective: to control cancer and keep the men alive. This is the only study with sufficient power to compare these two options in this setting.”
Speaking from the audience, Ian F. Tannock, MD, FRCPC, PhD, Princess Margaret Hospital, Toronto, said, “My concern is that the investigators did not show that intermittent androgen deprivation is inferior. The confidence interval clearly includes 1.0, so there is no significant difference in survival between the arms. You did not prove noninferiority, but that is not the same thing as showing inferiority. It is dangerous to conclude that intermittent therapy is inferior. I agree we should discuss this trial with patients, but in my opinion, intermittent therapy remains a valid option for metastatic prostate cancer.”
In response, Dr. Hussain said, “The point is that the study was designed to assess if intermittent therapy is noninferior. The data clearly show that intermittent therapy failed to meet the prespecified criteria for noninferiority, which specified that the upper bound of the confidence interval exclude 1.2. This is why we do randomized trials—so that we can use evidence in counseling patients, not our biases. Furthermore, in my presentation, I was very careful to point out that the subgroup analysis is exploratory. Patients need to hear the evidence in total to make their decisions. Prostate cancer therapy is not necessarily ‘one-size-fits-all’.”
Another attendee said, “These findings could be consequences of a type 1 or type 2 error. We should not reject a treatment that improves quality of life, decreases costs, and spares patients from frequent contact with doctors.”
Another oncologist in the audience said that using an arbitrary confidence interval to call a treatment inferior does not make clinical sense. “You have to consider the individual patient. If a patient wants extra survival at all costs, that is one scenario. But if a patient doesn’t want to increase his frailty and suffer the side effects of continuous therapy, that is another scenario. The longest survival is not necessarily the best outcome.”
Dr. Oh, in his plenary discussion, had suggested that the amount of time that patients spent off of hormone therapy on the intermittent arm was approximately one-third, and that testosterone recovery often takes months. The quality-of-life data presented by Moinpour et al in the poster discussion session at this meeting suggested modest improvements in sexual function, libido, and emotional functioning in the intermittent arm.1
Lawrence H. Einhorn, MD, Lance Armstrong Foundation Distinguished Professor of Medicine at Indiana University School of Medicine, Indianapolis, called it a “scare tactic” to say that patients with minimal risk will have decreased survival on intermittent therapy. “It would be a mistake to use data from an unplanned subset analysis to guide treatment decisions. Minimal-risk disease is an artificial designation. It makes no biological sense and doesn’t advance the discussion,” he said.
“With any treatment in any cancer, there are harms and benefits. You have to ask yourself whether there may be a minimal benefit with continuous androgen deprivation, but it might be a quality-of-life issue for patients who will want to go off hormonal therapy until the PSA is rising,” Dr. Einhorn added.
Dr. Oh said the discussion about this study will continue. He acknowledged that the findings concerning extensive vs minimal disease may or may not be real. “The basic issue is whether we have enough consensus to say a treatment is standard of care,” he added. “I would submit that this study established continuous androgen deprivation as standard of care, and future studies with newer agents, such as abiraterone and MDV3100, should build on that.” ■
Disclosure: Drs. Tannock and Einhorn reported no potential conflicts of interest.
1. Moinpour C, Berry DL, Ely B, et al: Preliminary quality-of-life outcomes for SWOG-9346: Intermittent androgen deprivation in patients with hormone-sensitive metastatic prostate cancer (HSM1PC)—phase III. 2012 ASCO Annual Meeting. Abstract 4571. Presented June 4, 2012.