A randomized, double-blind, placebo-controlled phase II study of maintenance therapy with tasquinimod in patients with metastatic castration-resistant prostate cancer responsive to or stabilized during first-line docetaxel chemotherapy

Abstract

Background

This phase II study was conducted to assess clinical efficacy of tasquinimod maintenance therapy in patients with metastatic castrate-resistant prostate cancer not progressing during first-line docetaxel-based therapy.

Patients and methods

Patients were randomly assigned (1 : 1) to receive tasquinimod (0.25–1.0 mg/day orally) or placebo. The primary end point was radiologic progression-free survival (rPFS); secondary efficacy end points included: overall survival (OS); PFS on next-line therapy (PFS 2) and symptomatic PFS, assessed using the Brief Pain Inventory (BPI) questionnaire and analgesic use. Quality of life was measured by the Functional Assessment of Cancer Therapy-Prostate (FACT-P) questionnaire and by the EuroQol-5 Dimension Quality of Life Instrument (EQ-5D). Adverse events were recorded.

Results

A total of 219 patients were screened and 144 patients randomized. The median duration of treatment was 18.7 weeks (range 0.6–102.7 weeks) for the tasquinimod arm and 19.2 weeks (range 0.4–80.0 weeks) for the placebo arm. Median (90% CI) rPFS was 31.7 (24.3–53.7) and 22.7 (16.1–25.9) weeks in the tasquinimod and placebo arms, respectively [HR (90% CI) 0.6 (0.4–0.9), P = 0.0162]. The median OS was not reached because only 14 deaths occurred by the cut-off date. No statistically significant differences between treatment arms were noted for symptomatic PFS, PFS 2, BPI score, FACT-P score, or EQ-5D. The incidence of any treatment emergent adverse event (TEAE) was similar in the tasquinimod and placebo arms (97.2% versus 94.3%, respectively), whereas severe TEAEs (NCI-CTC Grade 3–5) incidence was higher in the tasquinimod group (50.7% versus 27.1%).

Conclusions

Randomized trials testing new drugs as maintenance can be successfully conducted after chemotherapy in castrate-resistant prostate cancer. Maintenance tasquinimod therapy significantly reduced the risk of rPFS by 40%.

ClinicalTrials

gov identifier NCT01732549.