- Response rates for chemotherapy in metastatic breast cancer of 40-70%, with survival benefits in the adjuvant setting
- Response rates for chemotherapy in metastatic colorectal cancer of 20-40%, with survival benefits in the adjuvant setting
- Docetaxel combined with ADT has improved OS in advanced prostate cancer [1-2]
For this trial, a total of 376 patients were randomized to receive either six cycles of adjuvant docetaxel 75mg/m2 every three weeks without continuous prednisone (Arm A, n = 188) or surveillance (Arm B, n = 188) after radiotherapy. Neoadjuvant/adjuvant ADT was mandatory for all patients. The primary end-point was a rising PSA ≥ 2 ng/ml above the nadir PSA value. Intermediate or high-risk prostate cancer was defined as one of the following:
- T2 with Gleason 4+3, PSA 10-70 ng/mL
- T2, Gleason 8-10, ≤70 ng/mL
- Any T3
All six cycles of docetaxel were completed in 147 (78.2%) of patients in arm A, and remaining baseline characteristics were comparable between the two groups. Overall, 75.0 % had T3 disease, and 46.3% had Gleason 8-10 disease. Over a median follow up was 59.4 months (range 1 to 111 months). The primary endpoint was reached in 30.7% of patients: 31.0% in Arm A and 30.3% in Arm B. In a Kaplan-Meier analysis there showed no difference between the BDFS curves (p = 0.631) between treatment groups. The HR for the docetaxel arm vs surveillance arm was 1.14 (95%CI, 0.79-1.64). There were 52% of patients in Arm A that experienced treatment-related side effects from docetaxel, including 16% experiencing febrile neutropenia. No deaths were related to docetaxel treatment. There were 43 deaths during the trial (20 in Arm A and 23 in Arm B) of which 16 (9 in Arm A and 7 in Arm B) were secondary to prostate cancer. In a multivariable Cox regression model, Gleason score was the only significant predictor of PSA progression (HR 1.55, 95%CI 1.27-1.90).
Kellokumpu-Lehtinen concluded with several take-home messages for SPCG-13:
- Adjuvant docetaxel without prednisone did not improve BDFS after radical radiotherapy with ADT for intermediate or high-risk prostate cancer
- Biochemical progression was lower than expected at five years in both arms of the trial
- Docetaxel has proven to be effective in other prostate cancer disease states, but why it was not significant in the adjuvant setting deserves future preclinical and clinical focus
References:
1. Sweeney CJ, Chen YH, Carducci M, et al. Chemohormonal Therapy in Metastatic Hormone-Sensitive Prostate Cancer. N Engl J Med. 2015;373(8):737-746.
2. James ND, Sydes MR, Clarke NW, et al. Addition of docetaxel, zoledronic acid, or both to first-line long-term hormone therapy in prostate cancer (STAMPEDE): survival results from an adaptive, multiarm, multistage, platform randomised controlled trial. Lancet. 2016;387(10024):1163-1177.
Presented by: Pirkko-Liisa I. Kellokumpu-Lehtinen, MD, Department of Oncology, Tampere University Hospital, Tampere, Finland
Co-Authors: Marie Hjälm-Eriksson, Lennart Astrom, Timo Marttila, Camilla Thellenberg-Karlsson, Sten Nilsson, Widmark Anders, Teppo Huttunen, Claes Ginman; Capio St; Görans Hospital, Karolinska Institute, Stockholm, Sweden, Solna, Sweden; Uppsala University Hospital, Uppsala, Sweden; Seinajoki Central Hospital, Seinajoki, Finland; Umea University, Umea, Sweden; Karolinska University Hospital, Stockholm, Sweden; Department of Radiation Sciences, Umeå, Sweden; 4Pharma, Turku, Finland; Karlstad Central Hospital, Karlstad, Sweden
Written By: Zachary Klaassen, MD, Urologic Oncology Fellow, University of Toronto, Princess Margaret Cancer Centre, Twitter: @zklaassen_md at the 2018 ASCO Annual Meeting - June 1-5, 2018 – Chicago, IL USA