Washington, DC (UroToday.com) With the recent report of the CHAARTED study demonstrating a 13-month benefit in overall survival with docetaxel at first diagnosis of mHSPC (Sweeney et al NEJM 2015), chemotherapy has been moved forward in the treatment algorithm for newly diagnosed metastatic hormone sensitive prostate cancer (mHSPC). Armed with these data, there has been rapid adoption and increased use of chemotherapy earlier in the systemic therapy algorithm. In this session, Dr. Agarwal takes a critical look at the trials that have informed clinical practice in this setting.
GETUG AFU-15 trial randomized patients with mHSPC to androgen deprivation therapy (ADT) versus ADT + 9 cycles of docetaxel (Gravis et al, Lancet Oncol 2013). The primary endpoint was OS and there was no difference between the two arms for this endpoint. When stratified by disease severity, patients with high volume disease had trend toward improvement, although this did not reach statistical significance.
One arm of the STAMPEDE study randomized newly diagnosed or node positive or locally advanced prostate cancer patients to ADT+/- radiation therapy (standard of care, SOC) or
SOC +docetaxel (James et al, Eur Urol 2015). For patients with metastatic disease, a 22-month improvement in overall survival benefit was noted.
SWOG 9346 randomized 1749 patients with mHSPC to intermittent versus SOC of continuous ADT (Hussain et al, NEJM 2013). OS in the intermittent group was 5.1 years versus 5.8 years in the continuous ADT group. The confidence interval for OS exceeded the upper limit for non-inferiority and therefore continuous ADT remains the recommended approach. A subanalysis of this study demonstrated that PSA response at 7 months predicts survival. (Hussain et al, JCO 2006).
When one looks at CHAARTED, GETUG AFU-15, STAMPEDE, and SWOG 9346 together, the following observations can be made. Age at presentation in these studies was 64, 63, 65, and 70 years, respectively. Metastases were present at diagnosis in 71%, 73%, 72%, and 50% of patients, respectively. OS on ADT in high volume patients were 35 months, 32 months on the two former studies, but not reported on the two latter studies.
So is chemotherapy applicable to all? At the ASCO meeting earlier this year, Ian Tannock observed that the first three trials do not represent men with slowly progressive disease who develop metastases several years after diagnosis. Perhaps in these patients, chemotherapy makes sense and indeed docetaxel may be offered to these fit patients deemed to have high volume disease per clinical judgment. However, one should not feel compelled to offer chemo in patients who are unfit, hesitant about undergoing chemotherapy, have low volume disease, or fall into good prognosis group based on initial response to ADT (Higano et al, Nat Rev Urol 2015)
Neeraj Agarwal, MD
University of Utah
Benjamin T. Ristau, MD. from the Society of Urologic Oncology Meeting - December 2 - 4, 2015 – Washington, DC.
Fox Chase Cancer Center, Temple University Health System, Philadelphia, PA