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Browsing by Subject "metastatic castration-resistant prostate cancer"
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Item New Frontiers in Prostate Cancer Treatment: Are We Ready for Drug Combinations with Novel Agents?(MDPI, 2020-06-22) Aurilio, Gaetano; Cimadamore, Alessia; Santoni, Matteo; Nolè, Franco; Scarpelli, Marina; Massari, Francesco; Lopez-Beltran, Antonio; Cheng, Liang; Montironi, Rodolfo; Pathology and Laboratory Medicine, School of MedicineMedical treatment for metastatic castration-resistant prostate cancer (mCRPC) patients has progressively been evolving from a nonspecific clinical approach to genomics-oriented therapies. The scientific community is in fact increasingly focusing on developing DNA damage repair (DDR) defect-driven novel molecules, both as single-agent therapy and in combined treatment strategies. Accordingly, research is under way into combined drug therapies targeting different pathways, e.g. androgen receptor signaling (ARS) and poly (adenosine diphosphate [ADP]-ribose) polymerase (PARP) enzymes, immune checkpoint (IC) and PARP, IC, and ARS, and prostate-specific membrane antigen (PSMA). In an attempt to formulate evolving treatment paradigms in mCRPC patients, here we selected clinical research into patients undergoing therapies with emerging molecules, with particular emphasis towards PARP-, IC-, and PSMA-inhibitors. In order to focus on those molecules and drug combinations most likely to be translated into routine clinical care in the near future, we selected only those clinical studies currently recruiting patients. A PubMed search focusing on the keywords “prostate cancer”, “metastatic castration-resistant prostate cancer”, “DDR pathways”, “ARS inhibitors”, “PARP inhibitors”, “IC inhibitors”, “PSMA-targeting agents”, and “drug combinations” was performed.Item Randomized, Double-Blind, Placebo-Controlled Phase III Study of Tasquinimod in Men With Metastatic Castration-Resistant Prostate Cancer(American Society of Clinical Oncology, 2016-08-01) Sternberg C.; Armstrong A.; Pili R.; Ng S.; Huddart R.; Agarwal N.; Khvorostenko D.; Lyulko O.; Brize A.; Vogelzang N.; Delva R.; Harza M.; Thanos A.; James N.; Werbrouck P.; Bögemann M.; Hutson T.; Milecki P.; Chowdhury S.; Gallardo E.; Schwartsmann G.; Pouget J.-C.; Baton F.; Nederman T.; Tuvesson H.; Carducci M.; Department of Medicine, IU School of MedicinePURPOSE: Tasquinimod, a novel oral therapy targeting the tumor microenvironment, significantly improved progression-free survival (PFS) in a randomized, placebo-controlled phase II trial in men with metastatic castration-resistant prostate cancer (mCRPC). This phase III study was conducted to confirm the phase II results and to detect an overall survival (OS) benefit. PATIENTS AND METHODS: Men with chemotherapy-naïve mCRPC and evidence of bone metastases were assigned (2:1) to receive tasquinimod once per day or placebo until progression or toxicity. The primary end point was radiographic PFS (rPFS; time from random assignment to radiologic progression or death) per Prostate Cancer Working Group 2 criteria and RECIST 1.1. The study had 99.9% power to detect an rPFS hazard ratio (HR) of 0.6 with a two-sided alpha error of .05 and 80% power to detect a target HR of 0.8 for OS, the key secondary end point. RESULTS: In all, 1,245 patients were randomly assigned to either tasquinimod (n = 832) or placebo (n = 413) between March 2011 and December 2012 at 241 sites in 37 countries. Baseline characteristics were balanced between groups: median age, 71 years; Karnofsky performance status ≥ 90%, 77.3%; and visceral metastases, 21.1%. Estimated median rPFS by central review was 7.0 months (95% CI, 5.8 to 8.2 months) with tasquinimod and 4.4 months (95% CI, 3.5 to 5.5 months) with placebo (HR, 0.64; 95% CI, 0.54 to 0.75; P < .001). Median OS was 21.3 months (95% CI, 19.5 to 23.0 months) with tasquinimod and 24.0 months (95% CI, 21.4 to 26.9 months) with placebo (HR, 1.10; 95% CI, 0.94 to 1.28; P = .25). Grade ≥ 3 adverse events were more frequent with tasquinimod (42.8% v 33.6%), the most common being anemia, fatigue, and cancer pain. CONCLUSION: In chemotherapy-naïve men with mCRPC, tasquinimod significantly improved rPFS compared with placebo. However, no OS benefit was observed.