Prostate Cancer Therapies: From Fast-Track to Graveyard-Bound

An exploratory analysis favored whole pelvic vs. prostate-only radiation for overall survival (HR, 0.90; P = .57) and DSS (HR, 0.65; P = .15), but Dr. Mason called this finding hypothesis generating.

He remarked that combined ADT plus RT is enshrined in the European Association of Urology and National Comprehensive Cancer Network guidelines, "but that uptake is uncertain, and we have concerns as to whether this has been taken up as much as it should have been."

Dr. Small agreed with the authors’ conclusion that ADT and RT should be offered to all men with locally advanced prostate cancer suitable for RT, but said the absolute difference in 10-year overall-survival is modest, at 6%. Because accrual took place 10 years ago, the results also cannot be fully extrapolated to the increasingly common high-risk patients seen in the United States, who tend to be at a high grade and lower stage.

He pointed out that the combination arm had a 5% absolute increase in deaths because of secondary malignancies, which warrants exploration. "It makes you wonder what the radiation is doing here," he added.

Still, Dr. Small commended the authors for persevering with what he described as a tough study to do with a nonradiation arm. "This study is a demonstration of the power of the cooperative groups, and in an era of shrinking resources, points out that undersourcing the cooperative groups – as has been advocated by some – is shortsighted," he said.

Atrasentan Flops Again

Dr. David I. Quinn had the unenviable task of delivering the final word on atrasentan (Xinlay) as a prostate cancer therapy. The selective endothelin blocker failed as monotherapy in two previous phase III trials, and was so ineffective in combination with docetaxel that the phase III Southwest Oncology Group S0421 trial in advanced castration-resistant disease was halted early last year.

Dr. David I. Quinn

A new post hoc analysis from S0421 identified an 8-month survival benefit with atrasentan in a distinct subset of poor-prognosis patients with skeletal metastases and four bone metabolism biomarkers (median, 13 months vs. 5 months; P = .02).

Still, the drug proved futile when compared with docetaxel plus placebo in the entire cohort for time to progression (median, 9 months for both; HR, 1.03; P = .71) and overall survival (median, 18 months for both; HR, 1.04; P = .61). The 2-year progression-free survival was 18% in both groups, and overall survival rates were 37% and 38%, respectively.

"Endothelin blockade with currently available drugs such as atrasentan and zibotentan, which has three negative studies, is now a failed experiment," said Dr. Quinn, coleader of genitourinary medical oncology at the University of Southern California, Los Angeles. "It has been superseded by osteoblast-targeted therapy that actually works, like radium-223."

Dr. Parker reported consulting or advising for Algeta and receiving honoraria from Bayer; his coauthors reported financial relationships including employment with Algeta, which initiated the ALSYMPCA trial. Dr. Saad reported consulting or advising for and receiving honorarium and research funding from Amgen. Dr. Mason reported no disclosures. Dr. Quinn reported financial relationships with several firms. SWOG S0421 was supported by the Eastern Cooperative Oncology Group and Cancer and Leukemia Group B. Dr. Small reported consulting or advising for Dendreon and receiving research funding from Genzyme and Sanofi.