CurrentNeighborhood Health Plan of Rhode IslandPolicy N/A

Xtandi (enzalutamide) coverage criteria for prostate cancer

Defines accepted indications, continuation and exclusion criteria, and coding for enzalutamide (Xtandi) requests processed by Evolent for Neighborhood Health Plan of Rhode Island across commercial and government lines of business.

Policy Summary

PayerNeighborhood Health Plan of Rhode Island

PolicyXtandi (enzalutamide) coverage criteria for prostate cancer

Policy CodePolicy N/A

Change TypeAdministrative/template conversion and wording clarifications (non-material)

Effective DateN/A

Next Review DateN/A

Key ActionProvide documentation showing the indication is supported by FDA labeling, CMS compendia, NCCN/ASCO guidelines, or acceptable peer‑reviewed literature per Medicare Benefit Policy Manual Chapter 15.

SourceLink

POLICY UPDATE CHANGES

Converted to new Evolent guideline template (Feb 2025) and prior update clarified clinical settings for use with LHRH analog or after orchiectomy (Feb 2024).

1J-code listed for enzalutamide

5Lines of business applicable

160Single dose maximum limit (mg)

120Monthly maximum 40 mg capsules/tablets

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Authorization and Medical Necessity Criteria for Enzalutamide (Xtandi)

General authorization requirements

Authorization is allowed when supported by FDA labeling, CMS compendia, NCCN/ASCO guidelines, or acceptable peer-reviewed literature; continuation exceptions are described separately.

ALL of the following

Request documentation must be supported by one of: FDA approved product labeling, CMS‑approved compendia, NCCN, ASCO clinical guidelines, or peer‑reviewed literature meeting CMS Medicare Benefit Policy Manual Chapter 15 requirements.

Continuation requests exemption to Evolent policy

Continuation requests for a medication that would otherwise be not‑approvable are exempt if ALL of the following are met:

ALL of the following

Member has not experienced disease progression on the requested medication
Requested medication was used within the last year without a lapse of more than 30 days of having an active authorization
No additional medication(s) are being added to the continuation request

Prostate cancer — permitted indications

Xtandi (enzalutamide) may be used for prostate cancer in the following clinical settings when combined with ADT (GnRH analog or post‑orchiectomy) or as noted:

One of the following indications

Non‑metastatic castration‑resistant prostate cancer (M0 disease; no visible metastases on conventional imaging) AND PSA doubling time ≤ 10 monthsPSA doubling time ≤ 10 months
Metastatic castration‑sensitive or castration‑resistant prostate cancer
Non‑metastatic castration‑sensitive prostate cancer (nmCSPC) with high‑risk biochemical recurrence (high‑risk BCR)

nmCSPC (high‑risk BCR) definition (ALL must be true as applicable to define nmCSPC)

High‑risk BCR criteria (any of the following qualify)

Exclusion criteria / Not eligible

Requests meeting any of the following exclusion criteria should be denied/not approved:

ANY of the following

Member has disease progression while on or after taking enzalutamide or a similar androgen receptor signaling inhibitor (e.g., apalutamide, darolutamide)
Member has BRCA1 and BRCA2 positive metastatic castration‑resistant prostate cancer (mCRPC) — enzalutamide is excluded in combination with talazoparib for BRCA1/2
Enzalutamide is being used concurrently with other anti‑cancer therapies including abiraterone, cabazitaxel, docetaxel, sipuleucel‑T, apalutamide, or darolutamide
Dosing exceeds single dose limit of 160 mgSingle dose maximum 160 mg

Relevant Billing Codes

Drug J-codeHCPCS

J8999

Unclassified biologics/chemotherapy — enzalutamide

Prior Authorization, Documentation, and Denial Risks

Prior Authorization

Authorization supported by evidence

Provide documentation that the requested enzalutamide (J8999) use is supported by FDA approved product labeling, CMS‑approved compendia, NCCN or ASCO clinical guidelines, or peer‑reviewed literature that meets the requirements of the Medicare Benefit Policy Manual Chapter 15. Include the HCPCS code J8999 on the request.

Affected code: J8999

Documentation Required

Continuation authorization criteria

For continuation requests that would otherwise be not‑approvable, document that the member has not experienced disease progression on enzalutamide, that the medication was used within the last year without a lapse of more than 30 days of active authorization, and that no additional medication(s) are being added to the continuation request. Include the HCPCS code J8999 on the request.

Continuation exemption criteria: no disease progression; prior use within last year without >30‑day lapse; no additional agents added

Clinical and Quantity Thresholds

Thresholds

Single dose maximum160 mg

Monthly maximum quantity120 (40 mg) capsules/tablets or 60 (80 mg) tablets

PSA doubling time for M0 CRPC≤ 10 months

PSA doubling time for high‑risk BCR (nmCSPC)< 9 months

PSA (post‑radical prostatectomy)> 1 ng/mL

PSA rise above nadir (post‑radiation therapy)≥ 2 ng/mL

Testosterone level threshold≥ 150 ng/mL

Clinical Context

Enzalutamide (Xtandi) is an androgen receptor signaling inhibitor indicated across multiple prostate cancer settings. It may be used for non‑metastatic castration‑resistant prostate cancer (M0 CRPC) in members with no visible metastases on conventional imaging and a PSA doubling time ≤ 10 months, and for metastatic castration‑sensitive or castration‑resistant prostate cancer where clinically appropriate.

Enzalutamide is also permitted for non‑metastatic castration‑sensitive prostate cancer (nmCSPC) with high‑risk biochemical recurrence (high‑risk BCR). High‑risk BCR is defined by any of the following: PSA doubling time < 9 months, PSA > 1 ng/mL after radical prostatectomy, PSA ≥ 2 ng/mL above the nadir after radiation therapy, or testosterone ≥ 150 ng/mL. Members treated with enzalutamide for nmCSPC may receive it with or without a concurrent GnRH analog.

Combination use of enzalutamide with the PARP inhibitor talazoparib (Talzenna) is allowed for HRR gene‑mutated metastatic castration‑resistant prostate cancer (mCRPC) when the tumor harbors one of the specified HRR gene alterations: ATM, ATR, BARD1, BRIP1, CDK12, CHEK1, CHEK2, FANCA, FANCL, or RAD51L4. An explicit exception excludes combination enzalutamide + talazoparib for patients with BRCA1 or BRCA2–positive mCRPC. When used in combination, members should also receive concurrent androgen deprivation therapy, either with a GnRH analog or following bilateral orchiectomy.

Authorization and continuation of enzalutamide require documentation supported by FDA labeling, CMS‑recognized compendia, NCCN/ASCO guidelines, or acceptable peer‑reviewed literature per Medicare Benefit Policy Manual Chapter 15. Continuation requests for otherwise not‑approvable therapy are allowed only if the member has not progressed on the medication, prior use occurred within the past year without a lapse greater than 30 days of active authorization, and no additional agents are being added.

Dose and quantity limits apply: do not exceed a single dose of 160 mg or monthly quantities greater than 120 (40 mg) capsules/tablets or 60 (80 mg) tablets. Requests that conflict with exclusion criteria — for example, disease progression on enzalutamide or concurrent use with excluded anticancer therapies — may be denied.

Defined Terms

Definitions

nmCSPCNon‑metastatic castration‑sensitive prostate cancer

M0 CRPCNon‑metastatic castration‑resistant prostate cancer (no visible metastases on conventional imaging)

High‑risk BCRBiochemical recurrence with factors such as rapid PSA doubling time, PSA thresholds post‑local therapy, or elevated testosterone as listed in policy

Policy Changes

2025-02administrativeLatest

Converted to the new Evolent guideline template; replaces prior UM ONC_1228 Xtandi (enzalutamide) guideline.

2024-02clarification

Updated clinical settings verbiage clarifying enzalutamide use in combination with an LHRH analog or after orchiectomy (ADT).

Policy Summary

PayerNeighborhood Health Plan of Rhode Island

PolicyXtandi (enzalutamide) coverage criteria for prostate cancer

Policy CodePolicy N/A

Change TypeAdministrative/template conversion and wording clarifications (non-material)

Effective DateN/A

Next Review DateN/A

SourceLink

On This Page

PSA doubling time < 9 monthsPSA doubling time < 9 months

PSA > 1 ng/mL (post‑radical prostatectomy)PSA > 1 ng/mL

PSA ≥ 2 ng/mL above the nadir (post‑radiation therapy)PSA ≥ 2 ng/mL above nadir

Testosterone level ≥ 150 ng/mLTestosterone ≥ 150 ng/mL

Members receiving Xtandi for nmCSPC may be treated with or without a GnRH analog concurrently

Combination with talazoparib for HRR‑mutated mCRPC

May be used with talazoparib for HRR gene‑mutated metastatic castration‑resistant prostate cancer (mCRPC) for the following genes: ATM, ATR, BARD1, BRIP1, CDK12, CHEK1, CHEK2, FANCA, FANCL, or RAD51L4
Exception: BRCA1 and BRCA2 mutation positive mCRPC are excluded from combination use of enzalutamide + talazoparib
Members receiving enzalutamide and talazoparib should also receive a GnRH analog concurrently or have had bilateral orchiectomy

Monthly quantity exceeds maximum: 120 (40 mg) capsules, 120 (40 mg) tablets, or 60 (80 mg) tablets per monthMonthly maximum quantity: 120 (40 mg) capsules/tablets or 60 (80 mg) tablets

Investigational use or off‑label indication lacking sufficient evidence per CMS compendia or acceptable peer‑reviewed literature

Affected code: J8999

Denial Risk

Combination therapy and mutation exclusions

Do not request concurrent use of enzalutamide (J8999) with the listed excluded anti‑cancer therapies; do not request combination enzalutamide + talazoparib for members with BRCA1 or BRCA2 positive mCRPC — requests meeting these conditions are exclusionary and may be denied.

Excluded concurrent therapies: abiraterone, cabazitaxel, docetaxel, sipuleucel‑T, apalutamide, darolutamide
Combination exclusion: enzalutamide + talazoparib for BRCA1/2 positive mCRPC
Affected code: J8999

Documentation Required

Dose and quantity limits

Ensure dosing and quantity do not exceed policy limits: single dose must not exceed 160 mg, and monthly quantities must not exceed the stated capsule/tablet maximums. Overruns are exclusionary and may lead to denial. Include HCPCS code J8999 on dosing documentation.

Single dose maximum: 160 mg
Monthly maximums: 120 × 40 mg capsules; 120 × 40 mg tablets; 60 × 80 mg tablets
Affected code: J8999