A randomized, double blind, placebo controlled phase 2 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 endpoint was radiologic progression-free survival (rPFS); secondary efficacy endpoints 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 (AEs) 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 = .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 AE (TEAE) was similar in the tasquinimod and placebo arms (97.2% v 94.3%, respectively) while severe TEAEs (NCI-CTC Grade 3-5) incidence was higher in the tasquinimod group (50.7% v 27.1%).

Conclusions

Randomized trials testing new drugs as maintenance can be successfully conducted after chemotherapy in CRPC. Maintenance tasquinimod therapy significantly reduced the risk of rPFS by 40%.ClinicalTrials.gov identifier NCT01732549