Tasquinimod Improves OS, PFS in CRPC, Data Show

Andrew J. Armstrong, MD

Tasquinimod, an experimental immunotherapy and anti-angiogenic agent, prolongs not just progression-free survival (PFS) but also overall survival (OS) in certain men with castration-resistant prostate cancer (CRPC), investigators have found after following participants in a phase II trial for a median 37 months.

More than 2 years after reporting that patients who participated in the randomized, placebo-controlled trial experienced improved PFS on tasquinimod, investigators led by a doctor at the Duke Cancer Institute published data November 19 indicating that the secondgeneration oral quinoline-3-carboxamide analog had also sparked improvements in OS. The latest results appeared in the journal Clinical Cancer Research.¹

Men with metastatic CRPC can be treated with sipuleucel-T, docetaxel, cabazitaxel, and/or abiraterone acetate, all of which have been shown to improve overall survival. However, treatments that slow metastatic progression and postpone the need for chemotherapy “are sought by both patients and healthcare providers,” investigators said in discussing the initial results of the trial in January 2012.

Tasquinimod works by binding to S100A9, which has a role in cancer through myeloid-derived suppressor cell function, the authors wrote. Tasquinimod also blocks angiogenesis.

In the study, 201 men with minimally symptomatic, metastatic CRPC were assigned in a 2:1 ratio to tasquinimod or placebo. OS results were evaluated after 111 deaths.

Median OS was 33.4 months in the tasquinimod group versus 30.4 months for those taking placebo, investigators Armstrong et al reported. Results were best for the subgroup of 136 men in the study who had bone metastases; they experienced a 34.2 month OS as compared to 27.1 months for those who took placebo, the authors wrote.

PFS lasted an average 7.6 months for men taking tasquinimod, as compared with 3.3 months for those on placebo; among men with bone metastases, those numbers rose to 8.4 months in the experimental group versus 3.4 months in the control group, Duke reported in an announcement about the findings.²

Based on a multivariable analysis, patients in the study who took tasquinimod had an adjusted hazard ratio of 0.52 for PFS (95% confidence interval [CI], 0.35-0.78; P = .001) and an adjusted hazard ratio of 0.64 for OS (95% CI, 0.42-0.97; P = .034), the researchers found. Time to symptomatic progression improved on tasquinimod with a hazard ratio of 0.42 and a P value of .039, they wrote.

The investigators described toxicities associated with tasquinimod as mild, with improvements occurring over time. Symptoms included mild gastrointestinal problems, pains in muscles and joints, and fatigue, according to the Duke article.

The team conducted exploratory biomarker studies at baseline and throughout the study to help identify predictors of benefit with tasquinimod.

“Biomarker analyses suggested a favorable impact on bone alkaline phosphatase and lactate dehydrogenase over time and a transient induction of inflammatory biomarkers, VEGF-A, and thrombospondin-1 levels with tasquinimod,” the investigators reported. “Baseline levels of thrombospondin-1 less than the median were predictive of treatment benefit.”

The study’s findings indicate that, in this population, prolonging PFS with tasquinimod may lead to a survival advantage, especially in men with skeletal metastases, and that the agent has a favorable risk/benefit ratio, the authors wrote.

Based on those findings, tasquinimod is being tested in a phase III trial in men with CPRC and bone metastases. According to Duke, it is likely the drug will also be tested in other cancers.

References

1. Armstrong AJ, Haggman M, Stadler WM, et al. Long-term survival and biomarker correlates of tasquinimod efficacy in a multicenter randomized study of men with minimally symptomatic metastatic castration-resistant prostate cancer. Clinical Cancer Research. Published online ahead of print, November 13, 2013.
2. Duke Medicine. Oral Drug May Improve Survival in Men with Metastatic Prostate Cancer. DukeHealth.org. http://tinyurl.com/nw4pj2b. Published November 13, 2013. Accessed November 26, 2013.