Vol. 9 • No. 1 • 2016
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Taxanes retain efficacy against mCRPC resistant to AR-antagonists
IN THIS ISSUE
Cancer prevention field riding high into the new year
BY NEIL OSTERWEIL Frontline Medical News
AR-V7 may potentially serve as a treatment
At the Genitourinary Cancers Symposium, San Francisco T he variant, labelledAR-47, is a truncated form of the androgen receptor that is missing the ligand- binding domain, to which both androgens and androgen receptor inhibitors such as abiraterone and enzalutamide normally bind. AR-V7 has been detected in about one-third of men with metastatic castration-resistant prostate cancer (mCRPC). But a study of circulating tumour cells (CTCs) from 37 men with mCRPC shows that patients whose tumour cells are positive for AR-V7 retain their sensitivity to taxanes. “In this particular study, there was a 41% re- sponse rate to taxanes if a man was AR-V7-positive, compared to a 0% response to abiraterone or en- zalutamide in this setting,” said Dr Emmanuel S. Antonarakis from the Johns Hopkins Sidney Kimmel Comprehensive Cancer Centre, Baltimore. Dr An- tonarakis presented the study in a briefing prior to its presentation in a poster session at the Genitourinary Cancers Symposium sponsored by the American Society of Clinical Oncology. Testing for the presence of AR-V7 could in the future help guide clinicians when choosing thera- pies for men with mCRPC, Dr Antonarakis said. The investigators used a quantitative
reverse-transcriptase polymerase chain reaction (qRT-PCR) assay selection marker for men with metastatic castration- resistant prostate cancer seeking therapy with either taxanes or enzalutamide/ abiraterone.
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had significantly better progression-free survival when treated with taxanes, compared with androgen receptor antagonists. The hazard ratio (HR) for PFS with taxanes was 0.21 (P = 0.003). In contrast, PFS was similar for AR-V7-negative men treated with either taxanes or abiraterone/enzalutamide. “AR-V7 may potentially serve as a treatment se- lection marker for men with metastatic castration- resistant prostate cancer seeking therapy with either taxanes or enzalutamide/abiraterone. However, be- fore the data become clinically actionable, we need to prospectively validate this finding in at least one multicentre clinical trial,” Dr Antonarakis said. He noted that there is currently no commercial assay for AR-V7.
to detect and quantify levels of AR-V7 in the CTCs of 37 men with mCRPC who were scheduled to start taxane-based chemotherapy with docetaxel or cabazitaxel. For the primary endpoint of a prostate specific antigen (PSA) response, they found that 7 of 17 men (41%) who were positive for AR-V7 had a response to taxane therapy, compared with 13 of 20 (65%) men with the wild type of the androgen receptor (that is, AR-V7 negative). The difference in response rates between AR-V7-positive and -nega- tive men was not significant. When they included data from an earlier study of 62 men treated with abiraterone or enzalutamide, the investigators found that AR-V7-positive men
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Nonalcoholic fatty liver disease linked to liver cancer without cirrhosis
had cirrhosis, compared with 91% of patients with chronic HCV infection, 92% of HCV-infected pa- tients, and 88% of patients with an alcohol use disorder. Notably, the odds of HCC in the absence of cirrhosis were more than five times higher when patients had NAFLD (odds ratio [OR], 5.4; 95% confidence interval [CI], 3.4–8.5) or metabolic syndrome (OR, 5.0; 95% CI, 3.1–7.8) compared with HCV infection. Patients with cirrhosis often go unscreened for HCC even though they are at greatest risk of this can- cer. Therefore, trying to screen all patients with NAFLD for HCC would be “logistically impractical,” particu- larly when the absolute risk of HCC in noncirrhotic patients is unknown and no one has examined the best ways to screen this population, the investigators said. Instead, clinicians could prioritise screening and treating NAFLD patients for diabetes mellitus and obesity, both of which are associ- ated with HCC. “There is evidence to suggest that metformin reduces the
patients to this disease entity ( Arch Pathol Lab Med 2008;132:1761–6). But few studies have systematically examined risk factors for HCC with- out cirrhosis in the general population, the investigators said. Therefore, they randomly selected 1500 patients from the US. Veterans Affairs system who were diagnosed with HCC between 2005 and 2010 on the basis of histo- pathology or established imaging cri- teria ( Hepatology 2005;42:1208–36). They reviewed complete medical records for these patients, and classi- fied those who did not have cirrhosis according to the quality of supporting histology, laboratory, and imaging data ( Clin Gastroenterol Hepatol 2015. doi: 0.1016/j.cgh.2015.07.019). In all, 3% of the cohort had level 1 (“highest-quality”) evidence for not having cirrhosis, while another 10% had level 2 evidence for no cirrhosis, the investigators said. “Compared with HCC in the presence of cirrho- sis, these patients were more likely to have metabolic syndrome or NAFLD or no identifiable risk factor, and less likely to have alcohol abuse or HCV infection,” they added. Only two- thirds of NAFLD patients with HCC
BY AMY KARON Frontline Medical News From Clinical Gastroenterology and Hepatology A bout 13% of US veterans with hepatocellular carcinoma had no evidence of preexisting cirrhosis, according to a report published in the January issue of Clinical Gastroenter- ology and Hepatology. “The main risk factors for this entity were nonalcoholic fatty liver disease [NAFLD] or metabolic syndrome” – not hepatitis C virus infection [HCV], HBV [hepatitis B virus] infection, or al- cohol abuse, said Dr Sahil Mittal of the Michael E. DeBakey Veterans Affairs Medical Centre and Baylor College of Medicine in Houston. Screening all patients with NAFLD for hepatocel- lular carcinoma [HCC] is impractical, so studies should seek “actionable risk factors” or biomarkers that reliably identify NAFLD patients who are at particular risk of HCC, wrote Dr Mit- tal and his coinvestigators. Researchers have debated whether chronic HCV infection or alcohol abuse can lead to HCC in the absence of cirrhosis, while at least one study has shown that NAFLD can predispose
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risk of HCC among diabetics,” they added. “Studies of these and other risk factors of HCC among NAFLD patients with and without cirrhosis are needed.” Most patients in the study were male, potentially limiting the general- isability of the findings, the research- ers noted. The American National Cancer In- stitute, the Houston Veterans Affairs Health Services Research and Develop- ment Centre of Excellence, the Michael E. DeBakey Veterans Affairs Medical Centre, and the Dan Duncan Cancer Centre funded the study. The research- ers had no disclosures.
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