The oral immunotherapy tasquinimod improved radiographic progression-free survival (rPFS) in men with metastatic castration-resistant prostate cancer (mCRPC), but the drug failed to improve overall survival (OS), according to results from a large, multinational phase III trial.
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Median rPFS was 7.0 months (95% CI, 5.8-8.2 months) for the tasquinimod group and 4.4 months (95% CI, 3.5-5.5 months) for placebo (HR, 0.64; 95% CI, 0.54-0.75; P less than .001). However, median OS was similar for the two groups: 21.3 months (19.5-23.0) for tasquinimod and 24.0 months (21.4-26.9) for placebo (HR, 1.10; 95% CI, 0.94 to 1.28; P = .25). At a median follow-up of 30 months, 96% of patients had discontinued treatment, most commonly because of progression (radiographic and symptomatic) and adverse events (J Clin Oncol. 2016 June 13. doi: 10.1200/JCO.2016.66.9697).
The 36% reduced risk of progression with tasquinimod versus placebo confirmed the phase II trial results, but the significant rPFS benefit did not translate to improved OS. The authors note that among one of several explanations for the lack of OS benefit is the availability of effective salvage therapies, many of which were not available during the phase II study.
“The current availability of such agents (e.g., abiraterone and enzalutamide) may have had an impact on the course of disease because patients in the placebo group gained access before those in the tasquinimod group on account of their earlier withdrawal from study treatment. Indeed, posttreatment use of abiraterone and enzalutamide was more common among patients in the placebo group,” wrote Dr. Cora Sternberg, chair of the department of medical oncology at San Camillo Forlanini Hospital, Italy, and colleagues.
The randomized, double-blind, placebo-controlled phase III study enrolled 1,245 patients from 241 sites in 37 countries. Patients with prostate adenocarcinoma with evidence of bone metastasis who had not received cytotoxic chemotherapy for 2 years were randomly assigned 2:1 to receive tasquinimod (n = 832) or placebo (n = 413).
Radiographic- and PSA-based secondary outcomes favored tasquinimod over placebo. By contrast, symptomatically assessed outcomes, such as time to symptomatic progression, time to opiate use, and deterioration of QoL, favored placebo. A greater proportion of the tasquinimod group discontinued treatment because of adverse events (17.7% vs. 10.2%), mainly decreased appetite, fatigue, asthenia, or nausea.
Tasquinimod affects the tumor microenvironment to counteract tumor growth. Preclinical evidence suggests it has an inhibitory effect on myeloid-derived suppressive cells and M2-polarized tumor-associated macrophages. Identification of immunologic biomarkers may help patient selection and determination of a rational combination strategy, according to the authors. Due to the lack of OS benefit, further clinical development of tasquinimod in this patient population was not pursued.
Dr. Sternberg reported having financial ties to Pfizer, Novartis, Janssen Pharmaceuticals, Sanofi, GlaxoSmithKline, Bristol-Myers Squibb, Bayer HealthCare Pharmaceuticals, Astellas Pharma, Eisai, Exelixis, Medivation, Active Biotech, and Genentech. Several of her coauthors reported ties to industry sources.