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CTC AR-V7 Assay Shows Promise as Treatment Guide in mCRPC

Jason Harris
Published: Tuesday, Jul 17, 2018

Howard I. Scher, MD
Howard I. Scher, MD
An assay for nuclear-localized androgen receptor splice variant 7 (AR-V7) protein in circulating tumor cells (CTCs) identified patients with metastatic castration-resistant prostate cancer (mCRPC) who had better outcomes from treatment with taxanes, and those who did better with androgen receptor-signaling (ARS) inhibitors. AR-V7–positive patients had superior outcomes with taxanes while AR-V7–negative patents had better outcomes with ARS inhibitor treatment.1

For patients who were positive for AR-V7 according to the Oncotype DX AR-V7 Nucleus Detect test, developed by Epic Sciences, the median overall survival (OS) was 14.3 months with taxane-based chemotherapy compared with 7.3 months for those who received ARS inhibitors (HR, 0.62; 95% CI, 0.28-1.39;  =  .25).

Conversely, patients who were negative for AR-V7 had a superior median OS when treated with ARS inhibitors (19.8 vs. 12.8 months; HR, 1.67; 95% CI, 1.00-2.81; P  =  .05).

Investigators concluded that the assay may help physicians choose the appropriate treatment for this patient population.

“This liquid biopsy test addresses a critical unmet need at a decision point in management to predict and select the therapy that is most likely to extend a patient's life,” lead author Howard Scher, MD, co-chair of the Center for Mechanism Based Therapy and head of the Biomarker Development Initiative at Memorial Sloan Kettering Cancer Center, said in a statement.

“During the treatment of metastatic prostate cancer, physicians will now be able to use AR-V7 status to determine when a patient's cancer has become resistant to androgen receptor–directed therapy and will respond better to chemotherapy, enabling the patient to live longer,” he added.

Previous study results have shown that AR-V7 is linked with resistance to enzalutamide (Xtandi) and abiraterone acetate (Zytiga), ARS inhibitors demonstrated to improve survival in this patient population.2 Approximately 10% to 20% of chemotherapy-naïve men are refractory to ARS inhibitors.

Scher et al included blood samples from 142 patients undergoing a change in systemic therapy for progressive disease. Seventy-two samples were collected before initiation of taxane therapy and 70 before the start of therapy with an ARS inhibitor. Seventy men were deemed high risk per standard prognostic factors.

Patients were not randomly assigned to treatment, but treating physicians were blinded to the patient’s AR-V7 status and CTC count. Physicians elected to use ARS inhibitors more often as a second-line treatment and use taxanes for later lines of therapy.

Scher et al found that median age, hemoglobin levels, albumin levels, and the presence of lung and/or liver metastases before therapy did not affect treatment choice. However, patients in the taxane arm had higher levels of lactate dehydrogenase (245.0 vs 203.0 U/L;  < .001), PSA (133.4 vs 30.3 ng/mL;  < .001), and alkaline phosphatase (126.5 vs 9.5 U/L; P  =  .01).

Rates of AR-V7 positivity were similar between the validation (34 of 142; 23.9%) and training (31 of 123; 25.2%) cohorts.

Overall, patients in the ARS inhibitor arm had superior median survival time (16.0 vs 12.9 months), but investigators did not observe a significant difference in survival rates between the treatment groups (P  =  .18).

Investigators developed a patient-specific risk score from the training cohort and calculated estimated median survival based on AR-V7 status, risk score, and choice of treatment. The median risk score was –0.632.

Among high-risk AR-V7–negative patients, the median OS was superior for those treated with ARS inhibitors (16.9 vs 9.7 months; HR, 2.38; 95% CI, 1.12-5.06; P  =  .02). Taxanes induced superior median OS among high-risk AR-V7–positive patients (14.3 vs 5.6 months; HR 0.35; 95% CI, 0.14-0.88; P = .03).

There were not enough low-risk, AR-V7–positive patients to evaluate survival rates by biomarker result.

Study coauthor Ryan Dittamore, chief of medical innovation at Epic Sciences, said in a statement that investigators developed this study specifically to help patients and physicians when making treatment decisions.

“This question weighs heavily on doctors and patients, but now, with the Oncotype DX AR-V7 test, we can provide them the confidence to know whether continuing with hormonal therapy or switching to chemotherapy will result in better survival outcomes,” he said. “In addition, the survival benefit gained through the utilization of our AR-V7 test could make the test as valuable to a patient's outcome as a blockbuster cancer drug.”

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