June 2014, Vol 3, No 4
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.
Highest Response Rate to Date With a Third-Line VEGF Inhibitor, Pazopanib, in Metastatic Renal Cell Carcinoma
Almost 50% of patients with metastatic renal cell carcinoma (mRCC) had objective responses to third-line treatment with the angiogenesis inhibitor pazopanib, according to the results from a small clinical trial reported at the 2014 American Association for Cancer Research annual meeting. Overall, 12 of 28 patients achieved objective responses (including [ Read More ]
Preliminary results suggest that an investigational antibody-drug conjugate called DEDN6526A has activity against melanoma, including cutaneous, mucosal, and ocular melanoma, which is considered difficult to treat. The new drug comes on the heels of trastuzumab emtansine, the first antibody-drug conjugate approved by the FDA for the treatment of breast cancer. [ Read More ]