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

Mené sur 144 patients atteints d'un cancer métastatique de la prostate résistant à la castration et n'ayant pas progressé durant un traitement de première ligne à base de docétaxel, cet essai de phase II évalue, du point de vue de la survie sans progression radiologique et de la survie globale, l'efficacité d'un traitement d'entretien par tasquinimod

Résumé en anglais

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