June 2014, Vol 3, No 4

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Simple Blood Test Predicts Response to Enzalutamide in Patients With Prostate Cancer


Results from a preliminary study from a highly respected group of researchers suggest that a simple blood test for the androgen receptor splice variant-7 (AR-V7) in the AR gene can identify men with castrate-resistant prostate cancer (CRPC) who will not respond to enzalutamide. If these results are confirmed in a larger population, the test could help differentiate whether patients would benefit from this drug, avoid unnecessary costs, and allow patients to move on to an effective drug. The data were presented for the first time at the 2014 American Association for Cancer Research annual meeting.

“AR-V7 is detectable in circulating T cells in a subset of CRPC patients and seems to predict resistance to enzalutamide. We believe these data have immediate clinical implications in that we can steer patients who test positive for this splice variant away from enzalutamide and offer them chemotherapy and radiation,” said Emmanuel S. Antonarakis, MD, assistant professor of oncology, Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD. “Further, the availability of a blood biomarker for AR-V7 could fuel the development of novel AR therapies,” Antonarakis added.

The use of enzalutamide for CRPC in the pre­docetaxel space is off-label. However, approval for this indication may be forthcoming. Currently, 3 other therapies are approved for this indication: abiraterone plus prednisone, radium-223, and sipuleucel-T.

“Even though enzalutamide is considered a very effective drug for some patients, about 20% of patients do not respond,” Antonarakis said. He noted that many potential reasons for resistance to the drug have been proposed, but he and his team have focused on splice variants of the AR gene. “Our studies suggest that AR-V7 is the most important variant related to resistance to enzalutamide,” Antonarakis said.

A 2-part assay was used to detect AR-V7 in circulating T cells: the Dana Test Prostate Cancer Select and the AdnaTest ProstateCancer Select kits. The study enrolled 31 men with CRPC who were planning to initiate treatment with enzalutamide. Circulating T-cell samples were provided at baseline, time of response, and time of resistance. The data presented by Antonarakis were derived from baseline circulating T-cell samples.

Of the 31 patients, 12 (39%) had detectable AR-V7 in their circulating T cells. Among patients previously treated with abiraterone, the risk of detectable AR-V7 increased to 55%, whereas it was detectable in only 9% of abiraterone-naive patients.

According to the RECIST, no tumor shrinkage was seen in any patient with detectable AR-V7. Every patient who had a prostate-specific antigen (PSA) response was wild-type for AR-V7, whereas only 1 of the patients with detectable AR-V7 had a PSA response. The presence of detectable AR-V7 was associated with a 7-fold risk of PSA progression and an 8.5-fold risk of clinical progression.

A multivariate analysis identified 3 factors associated with lack of response: detectable AR-V7, baseline PSA level, and previous abiraterone treatment. The 2 factors associated with progression-free survival were the presence of AR-V7 and previous treatment with abiraterone.

The Last Word - June 30, 2014

PMO and the PMC – A Collaboration to Advance Precision Medicine

Introducing Dr Edward Abrahams, President of PMC, as the Author of The Last Word Since the inception of Personalized Medicine in Oncology (PMO), we have offered the department The Last Word in which we sum up thoughts on various overriding themes in the world of personalized medicine. In this thought-provoking [ Read More ]

Uncategorized - June 30, 2014

FGFR Inhibitor Shows Promising Anticancer Activity

Inhibition of fibroblast growth factor receptors (FGFRs) 1, 2, 3, and 4 is showing promise in the treatment of cancers driven by FGFR alterations, especially bladder cancer and lung cancer, according to phase 1 studies presented at the 2014 American Association for Cancer Research annual meeting. A phase 1 study, [ Read More ]