ASCO 2017: A randomized phase II study of pelareorep (REO) plus docetaxel vs. docetaxel alone in patients with metastatic castration resistant prostate cancer (mCRPC): Canadian Cancer Trials Group study IND 209
Prior in vitro studies using established prostate cancer cell lines have also demonstrated synergistic activity with microtubule targeting agents, and in particular with taxanes. In men with castration-resistant prostate cancer (CRPC), docetaxel chemotherapy has been a mainstay of treatment since 2004. However, alternative agents that target the androgen axis have been introduced in the past decade that have demonstrated survival benefit in the same population. In this particular study, the authors evaluate whether adding REO to docetaxel chemotherapy provides any oncologic benefit.
Study design:
This was a randomized, open-label Phase II study. Patients received docetaxel 75mg/m2 on day 1 of a 21-day cycle in combination with REO given as 3x1010 TCID50 IV daily on days 1-5 (arm A) or alone (arm B). Primary outcome was 12-week lack of disease progression (LDP) rate. Secondary outcomes included objective response rate (ORR), survival, circulating tumor cell (CTC) counts at 0, 6 and 12 weeks, and PSA response rate.
Results:
Eighty-five pts were included and randomized - median age 69, ECOG performance status (PS) was 0/1/2 in 31%/66%/3% of patients, and bone/regional lymph node/liver metastases were present in 98%/24%/6%. This represented a good mix of CRPC patients. Forty-one patients received combination therapy (Arm A) and 44 patients received docetaxel monotherapy (Arm B). Of these, 18 and 29 were alive at the time of the analysis, respectively.
While the median number of cycles delivered for arms A/B was similar (7 and 9), patients in arm A were less likely to receive the planned dose intensity of docetaxel compared to patients in arm B (51% vs. 76%). Adverse events (AE) were also more prevalent in arm A, including a higher rate of grade 4 febrile neutropenia.
The 12-week LDP was not significantly different between the groups (61% and 52.4% in A/B respectively, p = 0.51). Overall survival was worse in arm A vs. B (19.1 months vs. 21.1 months, respectively, p=0.06). No survival benefit of REO with D was found in any subset from the biomarker analysis.
Limitations:
1. More patients in arm A had poor prognostic factors for survival at baseline (median prognostic index 1.44 vs. 1.29). As patients were randomized, it is unclear how this bias was introduced. This may contribute to the worse OS, but not the LDP.
A sensitivity analysis for OS accounting for age and prognostic factors still demonstrated no significant difference between the arms.
Ultimately, with higher side effects and higher discontinuation rates, in conjunction with no significant survival benefit, REO cannot be recommended as a supplemental therapy for docetaxel in CRPC patients.
Presented By: Bernhard J. Eigl
Co-Authors: Eric Winquist, Dongsheng Tu, Sebastien J. Hotte, Christina M. Canil, Richard William Gregg, Muhammad Zulfiqar, Scott A. North, Susan Ellard, Joseph D. Ruether, Lyly H. Le, Ankineedu Saranya Kakumanu, Ashley Theis, Christopher M. Booth, Kylea R. Potvin, Kim N. Chi, Lesley Seymour
Institution(s): BC Cancer Agency, Vancouver, BC, Canada; London Health Sciences Centre, London, ON, Canada; Canadian Cancer Trials Group, Kingston, ON, Canada; Escarpment Cancer Research Institute, Juravinski Cancer Centre, Hamilton, ON, Canada; Ottawa Regional Cancer Centre, Manotick, ON, Canada; Cancer Centre of Southeastern Ontario, Kingston, ON, Canada; BC Cancer Agency, Abbotsford, BC, Canada; Cross Cancer Institute, Edmonton, AB, Canada; BCCA, Kelowna, BC, Canada; Tom Baker Cancer Centre, Calgary, AB, Canada; BC Cancer Agency, Surrey, BC, Canada; Allan Blair Cancer Center, Regina, SK, Canada; Division of Cancer Care and Epidemiology, Cancer Research Institute, Queen's University, Kingston, ON, Canada; University of Western Ontario, London, ON, Canada; British Columbia Cancer Agency, Vancouver, BC, Canada; Queen's University, Kingston, ON, Canada
Written By: Thenappan Chandrasekar, MD, Clinical Fellow, University of Toronto, Princess Margaret Cancer Centre
Twitter: @tchandra_uromd
at the 2017 ASCO Annual Meeting - June 2 - 6, 2017 – Chicago, Illinois, USA