Roberto Pili, MD
The investigational compound tasquinimod significantly postpones disease progression and increases progression-free survival (PFS) in men with minimally symptomatic, metastatic castration-resistant prostate cancer (CRPC), according to the results of a phase II study.
Roberto Pili, MD, with Roswell Park Cancer Institute in Buffalo, New York, and associates randomized 201 chemotherapy-naïve patients in a 2:1 ratio to either oral once-daily tasquinimod (0.25 mg/day escalating to 1.0 mg/day over 4 wk) or placebo. Tasquinimod is a second-generation oral quinoline-3-carboxamide analog.
Current treatment options for men with metastatic CRPC include autologous cellular therapy with sipuleucel-T, docetaxel, and cabazitaxel, and secondary hormonal manipulations such as abiraterone acetate. Although all of these therapies have been shown to improve overall survival, treatments that slow metastatic progression and postpone the need for chemotherapy “are sought by both patients and healthcare providers,” the investigators said.
The primary endpoint was the percentage of patients without disease progression at 6 months, defined by Response Evaluation Criteria in Solid Tumors (RECIST), Prostate Cancer Working Group 2 (PCWG2), or pain criteria, excluding prostate-specific antigen (PSA).
The PFS at 6 months was 69% in the tasquinimod group compared with 37% in the placebo group (P
The median PFS was 7.6 months and 3.3 months for the 2 groups, respectively (P
= .0042; hazard ratio, 0.57; 95% CI, 0.39-0.85). The investigators described the finding as a “clinically meaningful halving of the ongoing risk of progression or death over time over placebo” and said that it is on a par with or better than PFS improvements observed with current therapies for metastatic CRPC approved by the FDA.
After 6 months of treatment, 31% of tasquinimod patients had progressed compared with 63% of placebo patients.
Pili and colleagues pointed out that men with metastatic CRPC represent a diverse population that can be assigned to prognostic subgroups depending on the location of metastases (ie, visceral, bone, or lymph nodes), as defined by the PCWG2. Importantly, tasquinimod slowed disease progression in all CRPC subgroups.
Tasquinimod also had an acceptable safety profile. Most adverse events were temporary and reversible and could be managed with dose reductions or supportive measures, with treatment continued at the maximal tolerated dose.
Finally, the authors said that, to their knowledge, the study is “the first positive-controlled phase II trial in men with CRPC that successfully incorporated new PCWG2 guidelines, which deemphasize PSA changes in the evaluation of novel agents and require confirmatory bone scans to reduce the risk of early discontinuation because of bone scan flare.”
A phase III trial to further explore the use of tasquinimod in a pre-docetaxel, metastatic CRPC population is presently underway and has a target recruitment of 1200 patients.
Pili R, Häggman M, Stadler WM, et al. Phase II randomized, double-blind, placebo-controlled study of tasquinimod in men with minimally symptomatic metastatic castrate-resistant prostate cancer [published online ahead of print September 19, 2011]. J Clin Oncol. 2011;29(30):4022-4028.