At this year's annual meeting of the American Society of Clinical Oncology, a group from the University of Michigan led by Maha Hussain, MD reported results of an international phase III trial showing that intermittent hormonal therapy is less effective than continuous therapy in patients with metastatic prostate cancer who have minimal disease.
On average, patients with minimal disease spread who received continuous therapy lived for nearly 2 years longer than those receiving intermittent therapy. For patients who had extensive disease spread, those in the intermittent therapy arm of the trial lived about 6 months longer than those in the continuous therapy arm. However, the latter results were not found to be statistically significant.
According to Dr. Hussain, for the past ten years or so, “the conventional belief has been that intermittent therapy should be done in the ‘good prognosis’ patients, so what we’re seeing now is something unusual.”
Dr. Hussain presented research from S9346 (INT-0162), an international phase III trial that included more than 1,500 patients whose prostate-specific antigen (PSA) fell to 4 ng/ml or lower after 7 months on continuous hormonal therapy. The men were randomized to either continuous or intermittent therapy, and ultimately the men on intermittent therapy received half the dose received by those in the continuous therapy group. The primary objective of the study was to assess if overall survival with intermittent therapy achieved comparable survival with continuous therapy in men with metastatic prostate cancer.
Dr. Hussain explained the study’s rationale, saying, “It is virtually a fact that when patients go on hormone treatment, over 90% will go on progressing, and this progression happens because the cancer cells adapt. When you deprive them of the male hormone, the cells say, ‘Well, we don’t care.’ Some of them die, but some of them are injured and they begin to self-protect.”
She went on to say that when the researchers designed the trial the thinking was that it was best to deplete the androgen, and then, when the cells are injured, reintroduce the hormone so that the cells will stay addicted to it. In this way, clinicians hoped to continue to prolong the duration of response. In trials that tested this earlier on, there was no appearance of harm. Dr. Hussain thinks that the reason they were able to detect harm in this new study was because of the large patient sample and due to the fact that it contained the purest population with regard to disease stage.
After a follow-up of 9.2 years, men with minimal disease spread had a median overall survival of 7.1 years in the continuous group and 5.2 in the intermittent group. Conversely, those who had extensive disease spread had a median overall survival of 4.4 years in the continuous group and 5 years in the intermittent group. For men with extensive disease, intermittent therapy was found to be noninferior to continuous therapy, while in men with minimal disease continuous therapy is the preferred treatment.
Several new treatment agents have emerged since Hussain’s study began, and Hussain points out that “because of the new discoveries, there are trials being planned to bring in some of the new drugs that are hormonally based into this population, to see if we can push the bar up.” Hussain went on to say that “if you delay the cancer from progressing on primary hormone treatment—if you delay death, and then death occurs because of something else,”—unrelated to the cancer—“then the mission is accomplished in terms of controlling the cancer.”
1. Hussain M, Tangen CM, Higano CS, et al. Intermittent (IAD) versus continuous androgen deprivation (CAD) in hormone sensitive metastatic prostate cancer (HSM1PC) patients (pts): Results of S9346 (INT-0162), an international phase III trial. J Clin Oncol. 2012;30:(suppl; abstr 4).