In a phase III trial reported in the Journal of Clinical Oncology, Sternberg et al found that tasquinimod, an oral therapy targeting components of the tumor microenvironment, increased radiographic progression-free survival but not overall survival vs placebo in men with chemotherapy-naive metastatic castration-resistant prostate cancer. As a result, the investigators are not pursuing further clinical development of tasquinimod in this patient population.
In this double-blind trial, 1,245 patients with metastatic castration-resistant prostate cancer and evidence of bone metastases from 241 sites in 37 countries were randomized 2:1 between March 2011 and December 2012 to receive tasquinimod (n = 832) or placebo (n = 413) once daily. The starting dose was 0.25 mg/d for at least 2 weeks, with an increase to 0.5 mg/d for 2 weeks and then to 1 mg/d if tolerated.
Patients had a median age of 71 years, Karnofsky performance status was ≥ 90 in 77%, and 21% had visceral metastases. Median time since diagnosis was shorter in the tasquinimod group (46 vs 58 months). The primary endpoint was radiographic progression-free survival (on Prostate Cancer Working Group 2 and RECIST [Response Evaluation Criteria in Solid Tumors] 1.1 criteria).
At final analysis, median follow-up was 30.0 months in the tasquinimod group and 30.7 months in the placebo group, with 96% of patients having discontinued study treatment. Estimated median radiographic progression-free survival on central review was 7.0 months (95% confidence interval [CI] = 5.8–8.2 months) in the tasquinimod group vs 4.4 months (95% CI = 3.5–5.5 months) in the placebo group (HR = 0.64, P < .001). Median overall survival was 21.3 months (95% CI = 19.5–23.0 months) in the tasquinimod group vs 24.0 months (95% CI = 21.4–26.9 months) in the placebo group (HR = 1.10, P = .25).
Median time to the start of salvage therapy (11.4 vs 8.1 months, P = .001) and time to further cytotoxic therapy (25.8 vs 16.0 months, P = .021) were longer in the tasquinimod group. Few patients had received abiraterone (Zytiga) or enzalutamide (Xtandi) prior to the study; after withdrawal, abiraterone was used by 25% of tasquinimod and 31% of placebo patients, and enzalutamide was used by 8% and 12%. Docetaxel was used by 34% and 40%, respectively.
Grade ≥ 3 adverse events occurred in 42.8% of tasquinimod patients and 33.6% of placebo patients, with the most common in the tasquinimod group being anemia (8.3% vs 7.5%), fatigue (3.4% vs 2.2%), and cancer pain (3.3% vs 2.4%). The most common adverse events of any grade in the tasquinimod group were cancer pain (31.8% vs 31.4%), decreased appetite (30.1% vs 16.3%), nausea (26.7% vs 21.7%), and fatigue (26.1% vs 17.5%).
The investigators concluded: “In chemotherapy-naive men with metastatic castration-resistant prostate cancer, tasquinimod significantly improved [radiographic progression-free survival] compared with placebo. However, no [overall survival] benefit was observed…. On the basis of the lack of [overall survival] benefit observed in this study, further clinical development of tasquinimod in this patient population was not pursued.”
The study was supported by Active Biotech.
Michael Carducci, MD, of Johns Hopkins University School of Medicine, is the corresponding author of the Journal of Clinical Oncology article.
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