CurrentNeighborhood Health Plan of Rhode IslandPolicy N/A

Keytruda (pembrolizumab) — oncology indications and authorization criteria

Defines covered oncology indications, prior authorization documentation, exclusions, and authorization durations for pembrolizumab (Keytruda) for Neighborhood Health Plan of Rhode Island members.

Policy Summary

PayerNeighborhood Health Plan of Rhode Island

PolicyKeytruda (pembrolizumab) — oncology indications and authorization criteria

Policy CodePolicy N/A

Change TypeNo material changes noted

Effective DateN/A

Next Review DateN/A

Key ActionSubmit prior authorization with required documentation of tumor histology, staging, and relevant biomarker status (PD‑L1, MSI‑H/dMMR, or TMB‑H ≥10 mut/Mb) to support FDA‑approved or compendial indications.

SourceLink

POLICY UPDATE CHANGES

No material clinical or coverage changes in this revision.

20+FDA & compendial indications

6 monthsTypical authorization period

TMB≥10TMB threshold

CPS/TPSPD‑L1 thresholds referenced

Covered Indications and Authorization Criteria

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Urothelial carcinoma — continued treatment and BCG‑unresponsive clause

Authorization and continued treatment rules for urothelial carcinoma, including special provisions for BCG‑unresponsive non‑muscle invasive bladder cancer (NMIBC).

ALL of the following

Authorization of 6 months may be granted as a single agent for treatment of urothelial carcinoma when used in any of the following subtypes:
Subtypes / settings
- Urothelial carcinoma of the bladder in any of the following settings: - First line therapy for locally advanced or metastatic disease in members who are not eligible for any platinum containing chemotherapy. - Subsequent therapy (post‑platinum or other chemotherapy). - Treatment of members with high‑risk, non‑muscle invasive bladder cancer (NMIBC) with carcinoma in situ (CIS) when disease is BCG‑unresponsive, and member will not undergo cystectomy.
- Primary carcinoma of the urethra with locally advanced, recurrent or metastatic disease post‑platinum or other chemotherapy or for members who are not eligible for any platinum‑containing chemotherapy.
- Urothelial carcinoma of the upper genitourinary tract or urothelial carcinoma of the prostate with metastatic disease post‑platinum or other chemotherapy or for members who are not eligible for any platinum‑containing chemotherapy.
Authorization of 6 months may be granted for the treatment of stage II, recurrent, locally advanced or metastatic urothelial carcinoma in combination with enfortumab vedotin‑ejfv.

Prior Authorization, Documentation, and Denial Risks

Documentation Required

Breast cancer receptor testing required

Breast cancer receptor testing: confirm TNBC by documenting tumor testing negative for HER-2, estrogen, and progesterone receptors; include PD‑L1 expression report when required by indication (e.g., recurrent/metastatic TNBC).

TNBC requires documentation of negative HER-2, estrogen, and progesterone receptor testing.
Provide PD‑L1 testing result when the indication requires tumor PD‑L1 expression.

Documentation Required

Urothelial carcinoma reauthorization documentation

Urothelial carcinoma reauthorization: for requests when enfortumab vedotin combination is used, document absence of disease progression and no unacceptable toxicity; for high‑risk BCG‑unresponsive NMIBC reauthorization, document non‑persistence/non‑recurrence of disease. Include prior platinum eligibility or reason platinum was not appropriate when relevant.

For enfortumab vedotin-ejfv combinations, include evidence the member has not progressed and has not had unacceptable toxicity.
For high‑risk BCG‑unresponsive NMIBC, include documentation that disease is not persistent or recurrent to support continued authorization.

Step Therapy

Step / previous therapy considerations

Step/previous therapy considerations: requests must document prior lines of therapy and reasons for use in the current setting; exclude members with progression while on prior PD‑1/PD‑L1 therapy except specified melanoma exception; document prior platinum therapy or clinical rationale when platinum is not appropriate.

Document prior systemic therapies and line of therapy (first‑line, subsequent, adjuvant, etc.).
Requests are excluded for members who progressed on prior PD‑1/PD‑L1 therapy unless meeting the melanoma exception (combination with ipilimumab after progression on single‑agent anti‑PD‑1).
When indication requires post‑platinum or non‑platinum eligibility, include prior platinum use or clinical justification that platinum was inappropriate.

Prior Authorization

Subsequent therapy / intolerance — document progression or intolerance

Subsequent therapy / intolerance: when authorizing subsequent‑line or single‑agent use, document disease progression on prior regimens or intolerance to first‑line combinations; when claiming intolerance, provide clinical notes detailing adverse events leading to discontinuation.

For subsequent therapy requests, include documentation of disease progression on prior therapy or intolerance to prior regimens.
If claiming intolerance, submit clinical notes describing the adverse event(s) and why alternative agents were not used.

Prior Authorization

Subsequent / single‑agent therapy authorizations

Subsequent/single‑agent therapy authorizations: single‑agent use is allowed in many listed indications (cutaneous melanoma, NSCLC subsequent therapy, HNSCC, urothelial carcinoma, many MSI‑H/TMB‑H tumor types, RCC nonclear cell, adjuvant continuity in select cancers); include tumor histology, PD‑L1/MSI‑H/TMB results, prior treatment history, and line of therapy.

Single‑agent authorization examples: cutaneous melanoma (unresectable/metastatic), NSCLC single‑agent subsequent therapy for PD‑L1+ disease, HNSCC single‑agent first‑line for PD‑L1/MSI‑H/TMB‑H tumors, many MSI‑H/TMB‑H solid tumors as subsequent therapy.
Provide tumor histology, staging/setting, biomarker reports (PD‑L1, MSI‑H/dMMR, TMB‑H), and documentation of prior lines of therapy for all single‑agent requests.

Permitted Combination Regimens

Regimen	Indication / Setting	Coverage status
Pembrolizumab + pemetrexed + platinum (carboplatin or cisplatin)
First-line treatment of metastatic nonsquamous NSCLC (no EGFR/ALK aberrations); also neoadjuvant for resectable tumors ≥4 cm or node positive when given with platinum chemo then continued as adjuvant
Covered when FDA‑approved criteria and documentation are met

Regimen	Tumor type / setting	Coverage status
Pembrolizumab + carboplatin + paclitaxel (or paclitaxel protein‑bound)
First‑line treatment of metastatic squamous NSCLC
Covered when FDA‑approved criteria and documentation are met

Regimen	Tumor type / setting	Coverage status
Pembrolizumab + gemcitabine + cisplatin
Locally advanced unresectable, resected gross residual (R2) or metastatic biliary tract cancers
Pembrolizumab + axitinib or pembrolizumab + lenvatinib

Regimen	Indication / setting	Coverage status
Pembrolizumab (single agent)
Primary mediastinal large B‑cell lymphoma — relapsed or refractory disease; single‑agent use may be authorized
Pembrolizumab in combination with brentuximab vedotin

Regimen	Indication / reauthorization condition	Coverage status
Pembrolizumab + enfortumab vedotin‑ejfv
Stage II, recurrent, locally advanced or metastatic urothelial carcinoma — continued treatment reauthorization when member has not experienced disease progression or unacceptable toxicity
Reauthorization may be granted in 6‑month intervals (up to continuous limits when criteria met)

Testing Thresholds and Required Biomarker Evidence

PD-L1 thresholds (TPS/CPS) — summary values

PD-L1 Tumor Proportion Score (TPS)TPS ≥1% for NSCLC and select indications

PD-L1 Combined Positive Score (CPS)CPS ≥1 for multiple tumor types (e.g., HNSCC, cervical, gastric HER2+); CPS ≥10 where specified (e.g., esophageal squamous)

Context/usage notePD-L1 may be reported as TPS or CPS depending on tumor type and FDA‑approved test

Tumor Mutational Burden (TMB) threshold

TMB-H numeric threshold>= 10 mutations per megabase (mut/Mb)

Indication scopeApplies to adult and pediatric unresectable or metastatic solid tumors meeting TMB-H criteria (exceptions for pediatric CNS as noted)

Documentation requirementLaboratory report confirming high tumor mutational burden (≥10 mut/Mb) required where applicable

MSI-H / dMMR — biomarker requirement reference

Biomarker definedMSI‑H (microsatellite instability‑high) or dMMR (mismatch repair deficient) status required for multiple tumor‑agnostic and tumor‑specific indications

DocumentationLaboratory report confirming MSI‑H or dMMR tumor status required where applicable

Usage examplesMSI‑H/dMMR used for tumor‑agnostic approvals and specific cancers such as colorectal, gastric, biliary, pancreatic, endometrial

PD-L1 (CPS) thresholds called out in indications

CPS ≥1 usesCPS ≥1 required for HNSCC first‑line, cervical cancer indications, and select gastric/GEJ HER2+ settings

CPS ≥10 usesCPS ≥10 required for esophageal squamous cell carcinoma subsequent therapy and other specified squamous indications

DocumentationPD‑L1 tumor expression by CPS must be provided via FDA‑approved test when CPS thresholds are listed

TMB-H restated (≥10 mut/Mb) across tumor-agnostic and tumor-specific uses

TMB‑H numeric thresholdTMB‑H defined as ≥10 mut/Mb across tumor‑agnostic and tumor‑specific indications

Applies toUnresectable/metastatic solid tumors progressed after prior treatment and select tumor types (e.g., anaplastic thyroid, biliary, pancreatic, ovarian, testicular)

LimitationsSafety/effectiveness not established for pediatric TMB‑H CNS cancers (exclusion)

PD-L1 (CPS) specific notes for vulvar and TNBC scenarios

Vulvar cancer noteVulvar cancer: authorization if MSI‑H/dMMR/TMB‑H (≥10 mut/Mb) OR disease progressed on/after chemotherapy with tumor PD‑L1 CPS ≥1

TNBC noteTriple‑negative breast cancer: tumor must be confirmed TNBC (HER2/estrogen/progesterone negative) and tumor must express PD‑L1 (no numeric CPS threshold provided in the TNBC section)

DocumentationConfirmatory lab/pathology reports required for receptor negativity and PD‑L1 status in TNBC and CPS in vulvar cancer

TMB numeric threshold reference (repeat)

Numeric threshold>= 10 mut/Mb

Clinical applicationUsed to qualify tumors for single‑agent pembrolizumab in numerous tumor types (e.g., anaplastic thyroid, ovarian, pancreatic, testicular)

Required evidenceLaboratory report confirming TMB ≥10 mut/Mb must be submitted when applicable

Indication-Specific Line of Therapy

first-line | adjuvant | neoadjuvant | subsequent — top-level mapping

Mapping of first‑line, adjuvant/neoadjuvant, and subsequent therapy designations across tumor types.

First‑line / adjuvant / neoadjuvant / subsequent mapping: Policy specifies first‑line, adjuvant/neoadjuvant, and subsequent settings depending on tumor type and regimen (e.g., NSCLC first‑line PD‑L1+ and perioperative/neoadjuvant uses; gastric/esophageal first‑line combinations; RCC first‑line combinations with axitinib or lenvatinib; TNBC neoadjuvant + adjuvant; many tumor‑agnostic uses reserved for subsequent lines).

See chunks cited for tumor‑specific mapping

mixed — mapping with two top-level nodes

Mixed mapping with two top‑level nodes reflecting first‑line and subsequent uses across indications.

Mixed — first‑line and subsequent: Several tumor types include both first‑line and subsequent therapy authorization pathways (for example: NSCLC, HNSCC, urothelial carcinoma, gastric, esophageal/EGJ, and testicular cancer third‑line biomarker‑selected use).

Chunks 18,19,21,29,30,34

second-line | subsequent — mapping

Second‑line / subsequent therapy mapping — single top‑level node.

Second‑line / subsequent: Many indications are defined for subsequent or later‑line therapy, including anal carcinoma, HCC after sorafenib, thymic carcinoma when first‑line combos not tolerated, and small cell lung cancer relapsed/progressive disease.

Chunks 36,41,44,54

first-line | adjuvant | neoadjuvant mapping

First‑line, adjuvant, and neoadjuvant mappings where two top‑level nodes are present.

First‑line combinations and neoadjuvant/adjuvant: Examples include RCC first‑line combinations with axitinib or lenvatinib, and TNBC neoadjuvant in combination with chemotherapy followed by adjuvant single‑agent use for high‑risk early‑stage disease.

Chunks 43 and 52

subsequent — single top-level mapping

Subsequent therapy mapping — single top‑level node for various single‑agent subsequent uses.

Subsequent uses: Authorization of 6 months may be granted as single‑agent subsequent therapy for relapsed or progressive disease in multiple tumor types (e.g., small cell lung cancer, Kaposi sarcoma, others listed in Section IV).

Chunks 54,57

salvage therapy mapping

Salvage therapy mapping — single top‑level node for pediatric hypermutant glioma settings.

Salvage: Authorization of 6 months may be granted as adjuvant or salvage treatment for hypermutant pediatric diffuse high‑grade glioma or for recurrent/progressive disease.

Chunk 55

Key Biomarker Thresholds and Coding Facts

Tumor Mutational Burden (TMB) numeric threshold

TMB numeric threshold>=10 mutations/megabase (mut/Mb)

Policy noteDefines tumor mutational burden‑high (TMB‑H) for adult and pediatric unresectable/metastatic solid tumors eligible after prior treatment

ExclusionPediatric TMB‑H CNS cancers excluded from coverage due to unestablished safety/effectiveness

PD-L1 expression thresholds summary (TPS/CPS)

PD‑L1 TPSTPS ≥1% for NSCLC first‑line and other specified NSCLC settings (as determined by an FDA‑approved test)

PD‑L1 CPSCPS ≥1 for multiple tumor types (e.g., HNSCC, cervical, gastric HER2+); CPS ≥10 where specified (e.g., esophageal squamous)

ReportingPD‑L1 must be documented by an FDA‑approved test and included with prior authorization when applicable

TMB-H threshold (repeat)

TMB‑H threshold≥10 mutations per megabase (mut/Mb)

Applies toTumor‑agnostic TMB‑H indication and multiple tumor‑specific single‑agent uses

EvidencePrior authorization requires lab report confirming TMB‑H where indicated

PD-L1 CPS thresholds (CPS ≥1; CPS ≥10 where specified)

CPS ≥1PD‑L1 CPS ≥1 required for HNSCC first‑line and cervical cancer indications (and gastric HER2+ in some settings)

CPS ≥10 where specifiedPD‑L1 CPS ≥10 required for esophageal squamous cell carcinoma subsequent therapy and other enumerated squamous settings

DocumentationPD‑L1 CPS result must be provided from an FDA‑approved test when CPS thresholds are specified

TMB restated (>= 10 mut/Mb)

Restated threshold>= 10 mut/Mb

Use casesDesignates TMB‑H for policy‑eligible tumor types including ovarian, biliary, pancreatic, testicular, ampullary, occult primary, and others

Prior auth noteSubmit lab report confirming TMB ≥10 mut/Mb when applicable

Tumor mutational burden threshold note (>= 10 mut/Mb)

TMB threshold note>= 10 mutations/megabase (mut/Mb)

Policy scopeApplies broadly to TMB‑H tumor‑agnostic uses and to listed tumor‑specific indications such as ampullary adenocarcinoma

Documentation requirementLaboratory confirmation of TMB‑H required for prior authorization when indicated

Key Terms and Biomarker Definitions

PD-L1 TPS/CPS, MSI-H/dMMR, TMB-H definitions

PD‑L1 definitionsPD‑L1 reported as TPS or CPS depending on tumor type; TPS ≥1% for NSCLC and CPS thresholds (≥1, ≥10) used in other tumor types

MSI‑H / dMMR definitionMicrosatellite instability‑high (MSI‑H) or mismatch repair deficient (dMMR) tumor status used as a biomarker requirement across tumor‑agnostic and tumor‑specific indications

TMB‑H definitionTumor mutational burden‑high (TMB‑H) is defined as ≥10 mutations per megabase (mut/Mb)

TMB-H definition (>=10 mut/Mb)

TMB‑H numeric definition≥10 mutations per megabase (mut/Mb)

ApplicabilityUsed to define high tumor mutational burden for tumor‑agnostic and tumor‑specific coverage criteria

DocumentationLaboratory report confirming TMB‑H required for applicable prior authorizations

PD-L1 CPS definition and thresholds

PD‑L1 CPS descriptionCombined Positive Score (CPS) is the PD‑L1 metric used in multiple tumor types with thresholds such as CPS ≥1 or CPS ≥10

Clinical examplesCPS ≥1 for HNSCC and cervical cancer; CPS ≥10 for esophageal squamous and other specified settings

Testing requirementPD‑L1 CPS must be measured by an FDA‑approved test when required by the indication

MSI-H / dMMR definition

MSI‑H / dMMR definitionMSI‑H indicates microsatellite instability‑high; dMMR indicates mismatch repair deficient — both required biomarkers for multiple indications

UsageUsed for tumor‑agnostic approvals and in specific cancers (e.g., colorectal, gastric, biliary, pancreatic, ovarian, endometrial)

DocumentationSubmit laboratory report confirming MSI‑H or dMMR where applicable

TMB-H restated

TMB‑H restatedTMB‑H defined consistently in policy as ≥10 mut/Mb

SignificanceThreshold used across tumor‑agnostic and tumor‑specific coverage rules to identify candidates for pembrolizumab

Exclusion reminderPediatric TMB‑H CNS cancers excluded from coverage per policy exclusions

MSI-H / dMMR restated

MSI‑H / dMMR restatedMSI‑H/dMMR recognized as required biomarker for multiple indications; laboratory confirmation required

Role in tumor‑agnostic useMSI‑H/dMMR qualifies tumors for single‑agent pembrolizumab across tumor types when criteria met

DocumentationPrior authorization must include lab report confirming MSI‑H/dMMR where applicable

Triple-negative breast cancer (TNBC) definition

DefinitionTriple‑negative breast cancer (TNBC) = cancer testing negative for HER2, estrogen receptor, and progesterone receptor

PD‑L1 requirementPolicy requires tumor to express PD‑L1 for listed TNBC indications (PD‑L1 positivity required; numeric CPS not specified in TNBC section)

DocumentationPathology report confirming receptor negativity and PD‑L1 expression must be submitted

TMB‑H definition (repeat)

TMB‑H repeated definitionTMB‑H = ≥10 mutations per megabase (mut/Mb)

Policy applicationsUsed as eligibility criterion for tumor‑agnostic and tumor‑specific indications listed throughout the policy

Laboratory evidencePrior authorization requires lab confirmation of TMB‑H when applicable

MSI‑H / dMMR short definition

MSI‑H short definitionMSI‑H = microsatellite instability‑high; dMMR = mismatch repair deficient

Clinical roleShort biomarker descriptor for use in clinical documentation and prior authorization submissions

TestingLaboratory confirmation required when indicated by the coverage criteria