The LCD Title was changed from MolDX: Oncotype DX AR-V7 Nucleus Detect for Men with Metastatic Castrate Resistant Prostate Cancer (MCRPC) to MolDX: Androgen Receptor Variant (AR-V7) Protein Test.
Under Coverage Indications, Limitations and/or Medical Necessity changed verbiage to read: “Men with metastatic castration resistant prostate cancer (mCRPC) have multiple life extending, FDA- approved therapeutics options. However, there is no clear consensus on the therapeutic sequencing after initial exposure to an androgen receptor signaling inhibitors (ARSi), such as such as apalutamide, abiraterone, or enzalutamide or others to be developed. The response rate for a second ARSi, Abiraterone after Enzalutamide, or Enzalutamide after Abiraterone is lower than the initial exposure. Therefore, the most common clinical decision focuses on whether to start a second ARSi or taxane chemotherapy. It is therefore important to identify patients who will not respond to a 2nd ARSi in order to 1) avoid giving an ineffective therapy, and 2) delaying giving a more effective therapy, such as taxane chemotherapy, taxane combination therapies, Radium-223, PARP inhibitors, and platinum chemotherapy.
AR-V7 protein results from alternative androgen receptor (AR) mRNA splicing, which produces a constitutively active receptor that is associated with resistance to ARSi such as abiraterone and enzalutamide.1,2 A growing body of evidence suggests that patients with AR-V7 positive mCRPC do not benefit from ARSi therapy but may respond to taxanes, such as docetaxel.3-5 Supporting observations include that 1) AR-V7 positivity is associated with resistance to androgen receptor-targeted therapies4; 2) taxanes are equally effective in AR-V7–positive and AR-V7–negative mCRPC patients3,5 ; and 3) AR-V7 status may change during therapy.6 For these reasons, the National Comprehensive Cancer Network (NCCN) suggests that AR-V7 is a biomarker that may help guide therapy in mCRPC. 7
AR signaling requires that the AR transcriptional elements bind to DNA within the nucleus of the cancer cell. Therefore, the nuclear localization of the AR-V7 truncated protein may improve the clinical specificity of predicting ARSi resistance.8 Analysis of AR-V7 localization scoring guides has demonstrated that currently only nuclear AR-V7 protein expression improves the clinical specificity of predicting ARSi resistance, and importantly, is associated with improved overall survival with taxane chemotherapy.9”
Under Analysis of Evidence changed verbiage to read: “Numerous prior Medicare coverage decisions have considered the evidence in the hierarchical framework of Fryback and Thornbury 11where Level 2 addresses diagnostic accuracy, sensitivity, and specificity of the test; Level 3 focuses on whether the information produces change in the physician's diagnostic thinking; Level 4 concerns the effect on the patient management plan and Level 5 measures the effect of the diagnostic information on patient outcomes. To apply this same hierarchical framework to analyze an in vitro diagnostic test, we utilized the ACCE Model Process for Evaluating Genetic Tests.12 The practical value of a diagnostic test can only be assessed by taking into account subsequent health outcomes. When a proven, well established association or pathway is available, intermediate health outcomes may also be considered. For example, if a particular diagnostic test result can be shown to change patient management and other evidence has demonstrated that those patient management changes improve health outcomes, then those separate sources of evidence may be sufficient to demonstrate positive health outcomes from the diagnostic test.”
Under Bibliography references were revised to reflect changes in this LCD.
At this time 21st Century Cures Act will apply to new and revised LCDs that restrict coverage which requires comment and notice. This revision is not a restriction to the coverage determination; and, therefore not all the fields included on the LCD are applicable as noted in this policy.
- Provider Education/Guidance
- Creation of Uniform LCDs With Other MAC Jurisdiction