ASCO 2018: SPCG-13: A Randomized Phase III Trial Between Adjuvant Docetaxel and Surveillance after Radical Radiotherapy for Intermediate and High-Risk Prostate Cancer

Chicago, IL (UroToday.com) Pirkko-Liisa I. Kellokumpu-Lehtinen, MD, from Finland presented the first results of the SPCG-13 phase III RCT, testing docetaxel vs surveillance among men with intermediate and high-risk prostate cancer treated with radical radiotherapy. Dr. Kellokumpu-Lehtinen noted that the hypothesis for this trial was developed secondary to:

  1. Response rates for chemotherapy in metastatic breast cancer of 40-70%, with survival benefits in the adjuvant setting
  2. Response rates for chemotherapy in metastatic colorectal cancer of 20-40%, with survival benefits in the adjuvant setting
  3. Docetaxel combined with ADT has improved OS in advanced prostate cancer [1-2]
This randomized trial evaluated if six courses of docetaxel improve biochemical disease-free survival (BDFS) after radical radiotherapy for intermediate or high-risk prostate cancer.

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
Key exclusion criteria included: (i) M+ or N+ (either clinical or pathological), (ii) previous pelvic radiotherapy, (iii) previous chemotherapy within 5 years, and (iv) previous systemic corticosteroids within six months of randomization. Patients were followed for 5 years with PSA every 3 months for two years and thereafter every 6 months. The study was powered for 89% to detect a difference between groups and the sample size calculation accounted for T2/T3 distribution (12%/15% difference in BDFS was assumed for T2/T3 patients).

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
Clinical trial information: NTC006653848.

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
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