Top Takeaways from ASCO: Prostate Cancer

Docetaxel data require consideration of implementation methods in clinical practice.

Issue: August 10, 2015

CHICAGO – The efficacy of systemic docetaxel for the treatment of prostate cancer is “perhaps the most exciting data for prostate cancer” to come out over the last year, according to Jorge Garcia, MD, who leads the advanced prostate cancer research program at the Taussig Cancer Institute at the Cleveland Clinic. Here, Garcia discusses the Top Takeaways from two docetaxel studies presented at the ASCO 2015 Annual Meeting.

Results from RTOG 0521

This trial, authored by Howard M. Sandler, MD, MS, FASTRO, and colleagues, examined patients with high-risk prostate cancer who underwent local definitive radiation therapy, according to Garcia. Researchers hypothesized that the addition of adjuvant docetaxel and prednisone to long-term androgen suppression and radiation therapy would improve OS. The trial aimed to detect improvement in 4-year OS, which went from 86% to 93% with a 51% hazard reduction (HR = 0.49).

Five hundred sixty-two patients with a median age of 66 years were followed for a median of 5.5 years. Patients were randomized 1:1 to either radiation therapy plus the combination of LH-RH agonist and oral anti-androgen therapy or the same therapy plus radiation and androgen deprivation therapy, followed by six cycles of docetaxel, Garcia said. The length of duration of androgen deprivation therapy was 24 months.

According to Garcia, OS favored patients who received radiation plus 24 months of androgen deprivation therapy followed by six cycles of adjuvant docetaxel-based therapy. At 4 years, 93% of patients who received docetaxel-based therapy were alive (HR = .70; P = .04), compared with 89% of patients in the radiation and hormones-alone arm.

The trial also evaluated metastasis-free survival as well as PSA failure and biochemical failure, Garcia said. “Patients in the docetaxel arm had a longer time to biochemical reoccurrence as well as time to distant metastasis.”

Garcia said the “biggest question” is the interpretation of the results of this trial and how clinicians will incorporate this data into their routine clinical practice.

Jorge Garcia

“I think the challenge of this data is that time to distant metastasis or time to biochemical reoccurrence in the context of localized or locally advanced disease is not the most appropriate endpoint in clinical trials, as its impact in overall survival is unknown,” he said. “Also, if you look at the P value and hazard ratio in the trial, although there was a difference in overall survival, the primary endpoints of the studies were not met, as the expected HR was not met. The long-term follow-up for this trial is still immature, so we still need to look for a little bit longer follow-up to find out whether or not docetaxel in this setting is something we can really afford to do for all patients with locally advanced disease or if this is simply for a very selected group of patients destined to do poorly regardless of the primary therapy received.”

Results from STAMPEDE

This trial, authored by Nicholas David James, MD, PhD, and colleagues, assessed the addition of various treatment approaches to standard therapy for men with metastatic, hormone-naive/sensitive prostate cancer and also for men with high risk, locally advanced disease. The presentation focused on primary survival results for three research comparisons that recruited through all their intermediate analyses: use of docetaxel, use of zoledronic acid and a combination of the two medications. Stratified randomization allocated patients 2:1:1:1 to standard therapy (the control group), standard therapy plus docetaxel, standard therapy plus zoledronic acid or standard therapy plus a combination of the two.

“The uniqueness about the STAMPEDE trial is that two-thirds of the patients actually were randomized to multiple different arms with a sort of design that allows the trial to actually integrate new compounds that become more attractive agents through the natural history of drug development in prostate cancer,” Garcia told Healio.com. “This report looked at whether or not androgen deprivation plus docetaxel-based chemotherapy is better than androgen deprivation alone. On top of that, it also looks at the impact on bisphosphonate — in this case, zoledronic acid — against [ADT] alone and zoledronic acid plus docetaxel plus [ADT] against [ADT] and docetaxel alone.”

According to Garcia, the important question this trial raises is what the survival impact will be with regard to docetaxel.

“The data is quite impressive. Patients who received docetaxel-based chemotherapy plus [ADT] had a greater survival benefit compared with [ADT] alone,” Garcia said. “The difference is 22 months, which is quite striking. Again, if you think of these results, it actually complements results from CHAARTED trial (ECOG 3805) data that demonstrated a significant survival benefit when docetaxel is added upfront in men with advanced disease in the hormone-naive/sensitive setting.

“I think this data really puts the up-front chemotherapy controversy to rest. That means that, for any men who walk into the office with advanced prostate cancer in the hormone-naive state, or [who are] about to start hormones or [are] within 3 months of androgen deprivation initiation, those patients deserve to go on and get docetaxel-based chemotherapy. We are still defining who the specific subset of patients is that benefits the most from up-front chemo; low-volume vs. high-volume. Although this trial did not address this relevant question, in my opinion, any men with objective metastases should hear a very detailed discussion as to the role of chemotherapy for their disease.” – by Julia Ernst, MS

References:

James ND, et al. Abstract 5001.

Sandler HM, et al. Abstract LBA5002.

Both presented at: ASCO Annual Meeting; May 29-June 2, 2015; Chicago.

Disclosure: The RTOG 0521 study was funded by AstraZeneca, the NIH and Sanofi. STAMPEDE was funded in part by Astellas, Janssen, Novartis, Pfizer and Sanofi-Aventis. Garcia reports serving on an advisory board as a consultant for Sanofi.