CurrentCignaPolicy v081525

Pembrolizumab (Keytruda) prior authorization — coverage criteria and required request form

Defines prior authorization data collection and clinical assessment fields required by Cigna for pembrolizumab (Keytruda) across numerous tumor types and biomarker-driven indications; applies to providers requesting coverage/administration authorization. Affects prescribers, infusion sites, and specialty pharmacies.

Policy Summary

PayerCigna

PolicyPembrolizumab (Keytruda) prior authorization — coverage criteria and required request form

Policy CodePolicy v081525

Change TypeNo material change

Effective DateN/A

Next Review DateN/A

Key ActionSubmit the completed prior authorization request form with required J-code, medication details, and supportive documentation (genetic testing, chart notes, labs) via CoverMyMeds, SureScripts, or as directed.

SourceLink

POLICY UPDATE CHANGES

No material clinical or coverage changes in this revision.

~60listed tumor/diagnosis options on the request form

~7cancer areas with dedicated question branches

onlineCoverMyMeds / SureScripts

Accredonationally preferred specialty pharmacy

5 days

Trek Health ingests and normalizes Transparency in Coverage data and payer policy updates to give provider organizations a clear view of how commercial reimbursement behaves across markets, payers, and services. Our platform transforms raw payer disclosures into structured intelligence that supports contract evaluation, payer negotiations, and service line strategy. By combining market benchmarks with ongoing policy visibility, Trek helps teams identify variability, risk, and opportunity in commercial reimbursement. The result is faster insight, stronger negotiating positions, and more informed financial decisions.

standard prior authorization response time

Coverage Criteria and Condition-Specific Logic

Form-driven coverage criteria

Covered when ALL required documentation and form fields are provided and tumor-, biomarker-, stage-, prior therapy-, and intended-use-specific conditions on the request form are met.

General prerequisites: Required: completed request form with all required patient and physician demographic fields and attachments (supportive documentation such as genetic testing results, pathology/IHC/NGS reports, chart notes, and labs); indicate whether this is a new start or continuation and document response/progression status for continuation

See form instructions requiring supportive documentation; chunk 7

Biomarker-driven eligibility examples: Eligibility may be established by one of the following biomarker findings as indicated on the form: MSI-H/dMMR OR TMB-H (>=10 mutations per megabase) OR PD-L1 expression at tumor-specific CPS thresholds; attach test resultsTMB-H >= 10 mut/Mb; PD-L1 CPS thresholds per tumor

Form asks MSI-H/dMMR (chunk 7), TMB-H (chunk 11) and PD-L1 CPS (chunks 14,18)

Tumor- and use-specific conditions: For the requested diagnosis, provider must complete the branch-specific questions on the form documenting disease stage (resectable/unresectable/metastatic), prior lines of therapy and prior agents, whether pembrolizumab will be single-agent or combined with listed agents (e.g., pemetrexed+carboplatin, carboplatin+paclitaxel, carboplatin+fluoropyrimidine, lenvatinib, axitinib, trastuzumab, oral cyclophosphamide+bevacizumab), and additional condition-specific items (surgical candidacy, BCG history for NMIBC, radioactive iodine–refractory status for thyroid, performance status where required)

See tumor-specific conditional questions in chunks 13-14 and 17-23

Questionnaire-driven conditional coverage criteria

Coverage is determined by answers to tumor-specific questionnaire branches; each branch requires affirmative responses to the listed condition-specific items.

NSCLC (first-line, PD-L1+): Patient has NSCLC of the specified subtype; tumors express PD-L1 (CPS >=1 as indicated); when used first-line, document whether pembrolizumab is single-agent or used in combination (non-squamous: pemetrexed + carboplatin for first 4 cycles; squamous: carboplatin + paclitaxel/albumin-bound paclitaxel for first 4 cycles); document ALK, EGFR, and ROS1 testing status per form and stage where requestedPD-L1 CPS >=1

See chunks 18,17,19 for PD-L1, combination regimens, and genetic testing

NSCLC (metastatic, subsequent therapy): For metastatic subsequent-line NSCLC, document PD-L1 expression; if PD-L1 positive indicate ALK/EGFR/ROS1 status; if all negative, document prior platinum chemotherapy (carboplatin or cisplatin); if ALK/EGFR/ROS1 positive, document prior targeted TKI exposure as specified on the formPD-L1 CPS >=1 when applicable

See chunks 19 and 20 for subsequent therapy and prior agent questions

The request form documents the planned infusion site and related facility details and notes that, per some Cigna plans, infusion must occur in the lowest cost, medically appropriate setting. If the infusion is requested in a hospital outpatient-affiliated facility, the form asks whether the patient is a candidate for re-direction to an alternate lower-cost setting (for example, AIS, MDO, or home infusion) and requests a medical necessity rationale when re-direction is not appropriate. Providers should complete the facility and dispensing information and be prepared to justify higher-cost settings when applicable.

The form captures elective surgical options where clinically relevant (for example, for non‑muscle invasive bladder cancer it asks whether the patient is eligible to undergo cystectomy and whether the patient has elected not to undergo cystectomy). This item is recorded to document surgical candidacy and the patient’s decision; the form does not itself state coverage denial solely for electing against surgery but uses the response to inform the coverage determination.

The form requires submission of supportive documentation such as genetic testing, chart notes, and lab/test results. Requests submitted without the indicated supporting documents may be considered incomplete and insufficient for a coverage determination; providers should attach all relevant test reports and clinical records as prompted on the form to avoid delays or potential denial.

The form is structured to collect clinical information needed to determine medical necessity and does not include blanket statements declaring services not medically necessary. Instead, it requests the clinical details and required documentation that the reviewer will use to make a medical necessity decision.

Billing and Coding Fields

Form billing code fieldmixed

J-code

Field on form to supply the applicable J-code for the medication

inv-08: TMB-H threshold defined on form

TMB-H threshold on formDefined as tumor mutational burden-high (TMB-H): 10 or more mutations per megabase

Tumor types queried for TMB-HBreast, chordoma, chondrosarcoma, osteosarcoma, and other solid tumors as indicated on the form

Documentation requiredSupportive testing results (report showing mutations per megabase) must be attached with the request

Provider Required Actions and Submission Guidance

Prior Authorization

Form completion and drug procurement

Complete the Cigna prior authorization request form fully and indicate where the medication will be procured. The form must include the J-code, exact medication requested (strength/volume), quantity, duration, directions for use, and procurement details (e.g., Accredo Specialty Pharmacy, prescriber office stock, retail pharmacy, home infusion vendor).

Include J-Code and patient's current weight
Specify medication vial/strength (e.g., Keytruda 100mg/4ml) and quantity/duration
Select where medication will be obtained and supply specialty pharmacy details if applicable

Note

Submission method and response time

Submit requests via the methods listed on the form (CoverMyMeds, SureScripts, or as directed). Standard response time is 5 business days for prescription drug coverage requests. If the situation is urgent and may jeopardize life/health/function, mark Urgent on the form and call Cigna to expedite.

Submit online at www.covermymeds.com or via SureScripts in your EHR

Background and Purpose

This prior authorization request form is intended to collect the patient’s clinical features, disease stage, prior therapies, and biomarker status (for example, MSI‑H/dMMR, TMB‑H, and PD‑L1 results) so the payer can determine eligibility for pembrolizumab (Keytruda) across multiple tumor types. The form explicitly requires attachment of supporting documentation and concludes with a prescriber attestation acknowledging that the health plan or its designees may perform routine audits to verify the information provided.

Key Biomarker and Test Definitions

inv-18: MSI-H / dMMR definition and documentation requirement

DefinitionMSI-H (microsatellite instability-high) or dMMR (mismatch repair deficient) tumor status as indicated on the form

Which tumors prompted questionMSI-H/dMMR is queried across multiple solid tumors including CRC, BTC, ovarian, pancreatic, thyroid, endometrial, and others

Documentation requirementSupportive documentation (genetic testing, lab/test results, chart notes) must be attached with the request

inv-19: TMB-H — threshold definition as >= 10 mutations per megabase.

TMB-H threshold>= 10 mutations per megabase (as stated on the form)

Tumor-context notesForm asks TMB-H for breast cancer and for chondrosarcoma, chordoma, Ewing sarcoma, osteosarcoma, and other solid tumors not MSI-H/dMMR

Line of Therapy Criteria

first-line

First-line use must meet the form's first-line branch criteria and any tumor- and biomarker-specific prerequisites.

First-line vs subsequent indication capture: Form documents whether the requested use is first-line or subsequent therapy for many tumor types (including NSCLC, nasopharyngeal, cervical, gastric and others); for first-line use provider must indicate subtype, PD-L1 status when required, and planned combination regimen if applicable

See chunks 12,17,19

first-line | subsequent

When coverage may apply for either first-line or subsequent therapy, complete the relevant branch questions and document prior therapies or progression as requested.

First-line | subsequent therapy capture: Form asks whether medication is being used as first-line or subsequent therapy for multiple tumor types (NSCLC, BTC, pancreatic, ovarian, ATC and others); for subsequent use, document prior systemic treatments and whether disease progressed on those therapies; for first-line use, document PD-L1 and genetic testing status and planned combinations where applicable

Biomarker and Molecular Test Requirements

inv-23: MSI-H / dMMR biomarker requirement (form field).

Form fieldDoes your patient have microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) solid tumor? (Yes/No)

Follow-up branchingIf Yes, form asks whether tumor is colorectal cancer (CRC) or other listed diagnoses and further stage/prior therapy questions

Attachment requirementSupportive documentation (genetic testing, chart notes, lab/test results) must be attached when MSI-H/dMMR is indicated

inv-24: TMB-H biomarker requirement — >= 10 mutations per megabase.

Form field and thresholdDoes your patient have tumor mutational burden-high (TMB-H) tumors? Defined as 10 or more mutations per megabase

Tumor branches referencing TMB-H

Tumor- and Line-Specific Covered Regimens

Tumor / Indication	Allowed combination(s) on form	Notes / Line-specific use	Coverage status
Endometrial carcinoma	Carboplatin + paclitaxel; or single-agent pembrolizumab; or lenvatinib combinations (when dMMR/MSI-H negative)	Form asks whether used as single agent, in combination with carboplatin/paclitaxel followed by single-agent therapy, or with lenvatinib when not MSI-H/dMMR	Covered with criteria
Non‑squamous NSCLC	Pemetrexed (Alimta) + carboplatin for the first 4 cycles	Form specifically asks if medication is/will be used in combination with pemetrexed + carboplatin for first 4 cycles	Covered with criteria
Squamous / other NSCLC subtypes	Carboplatin + paclitaxel (or nab‑paclitaxel/Abraxane) when indicated; single agent options captured based on PD‑L1 status	Combination vs single‑agent choice depends on PD‑L1 and subtype per form branching	Covered with criteria
Esophageal / GEJ carcinoma	Platinum + fluoropyrimidine (e.g., carboplatin/cisplatin with capecitabine or 5‑FU) combinations	Form captures platinum/fluoropyrimidine combination selection and PD‑L1 (CPS) status for single‑agent use	Covered with criteria
Cutaneous SCC / SCCHN	Platinum + fluorouracil combinations when used first‑line with radiation or as indicated; single‑agent options when PD‑L1 positive	Form asks about curability, metastatic/unresectable status, and whether used first‑line with platinum/FU	Covered with criteria
Peritoneal / pleural mesothelioma	Pemetrexed + platinum (eg, pemetrexed/platinum) combinations	Form includes pemetrexed/platinum options for mesothelioma and peritoneal disease	Covered with criteria

Tumor / Indication	Specific combo(s) listed on form	Context / conditional questions	Coverage status
Non‑squamous NSCLC (first‑line)	Pemetrexed + carboplatin (Alimta + carboplatin) for the first 4 cycles	Form asks explicitly: 'Is/Was this medication (being) used in combination with Alimta (pemetrexed) and carboplatin for the first 4 cycles of therapy?'	Covered with criteria
Renal cell carcinoma (RCC)	Combination with axitinib (Inlyta) or lenvatinib (Lenvima)	Form asks whether patient will use pembrolizumab in combination with axitinib or lenvatinib and captures adjuvant intent, risk of recurrence, and nephrectomy status	Covered with criteria
Anaplastic thyroid carcinoma (ATC) / thyroid (TMB‑H or MSI‑H branches)	Combination with lenvatinib (Lenvima)	Form queries TMB‑H / MSI‑H status and whether disease is radioactive iodine‑refractory; lenvatinib combination is an option on the thyroid branch	Covered with criteria
Ovarian carcinoma (persistent or recurrent)	Oral cyclophosphamide + bevacizumab in combination with pembrolizumab	Form asks if patient will use pembrolizumab in combination with oral cyclophosphamide and bevacizumab and queries platinum‑resistance, CA‑125 trend, and prior chemotherapy	Covered with criteria

Policy Summary

PayerCigna

PolicyPembrolizumab (Keytruda) prior authorization — coverage criteria and required request form

Policy CodePolicy v081525

Change TypeNo material change

Effective DateN/A

Next Review DateN/A

SourceLink

On This Page

Stage- and management-specific NSCLC: For non-metastatic or stage-specific NSCLC branches, document stage (I–III), surgical candidacy or eligibility for definitive chemoradiation, and whether pembrolizumab is adjunctive following resection and platinum chemotherapy per form promptsstage-specific

See chunks 17 and 20 for stage and surgical candidacy questions

CLL/SLL: Document presence of del(17p)/TP53 mutation and whether patient is refractory to chemotherapy and unable to receive chemoimmunotherapygenetic testing

See chunk 20 for del(17p)/TP53 and chemo-refractory questions

NMIBC: Document high-risk disease features (including CIS), prior BCG exposure and BCG unresponsiveness when applicable, presence of papillary tumors, and cystectomy eligibility or reason for not undergoing cystectomyBCG attempted and unresponsive when applicable

See chunk 20 for NMIBC branch

RCC: Document whether pembrolizumab will be combined with axitinib or lenvatinib, whether use is adjuvant, intermediate-high or high risk of recurrence, and prior nephrectomy status per the RCC branchrisk status and prior nephrectomy

See chunk 21 for RCC-specific questions

BTC, thyroid, ovarian, pancreatic and other tumor-specific branches: For these tumor branches collect MSI-H/dMMR and TMB-H status, prior checkpoint inhibitor exposure, prior systemic therapy and progression, resectability or residual disease, disease stage (locally advanced vs metastatic), performance status where applicable, and whether single-agent or specific combination therapy is planned (e.g., lenvatinib for ATC; oral cyclophosphamide+bevacizumab for ovarian)MSI-H/dMMR or TMB-H where relevant

See chunks 22-23 for BTC, thyroid, ovarian, pancreatic conditional items

Standard turnaround: 5 business days

For urgent requests, check Urgent and call to request expedited review

Documentation Required

Documentation audit risk

Cigna or its designees may perform routine audits. By signing the attestation, the prescriber agrees the Health Plan may request medical records or other documentation to verify the accuracy of the information provided on the form.

Attestation and prescriber signature authorize potential medical record requests
Plan/designee may request supporting clinical documentation during audits

Prior Authorization

Required form fields and supporting documentation

Complete all required demographic and clinical fields on the form and attach supporting documentation. Required fields include patient identifiers (Cigna ID, DOB, address), prescriber identifiers (DEA, NPI or TIN), office contact, medication requested, J-code, directions, quantity, duration, ICD-10, and whether this is a new start or continuation.

All asterisked (*) items must be completed (e.g., Physician Name, DEA/NPI/TIN, Patient Name, Cigna ID, DOB)
Attach office contact, phone/fax, and prescriber signature/date
Provide ICD-10 and indicate new start vs continuation

Documentation Required

Required clinical documentation to attach

Attach pertinent clinical documentation with the request: disease stage, prior therapies (including dates, doses, and outcomes), performance status, tumor biomarker results (e.g., MSI-H/dMMR, TMB-H, PD-L1, ALK/EGFR/ROS1 status), chart notes, lab/test results, genetic testing reports, and full regimen details for concurrent agents.

Include disease stage and performance status
Attach prior therapy names, doses, dates, and reason for discontinuation/failure
Attach relevant biomarker/genetic testing and pathology reports

Prior Authorization

Alternative therapy documentation

For indications where a covered alternative exists (for example nasopharyngeal carcinoma where Loqtorzi/toripalimab may be a covered alternative), document prior use of the alternative or provide clear clinical rationale/contraindication if the alternative cannot be used. Include drug strength, dates taken, duration, response, intolerances, or contraindications.

If an alternative agent was tried, document strength, dates, duration, response, and adverse reactions
If the alternative was not tried, provide reasons/contraindications why it is not appropriate

Documentation Required

Prior therapy verification

The form includes questions to verify prior therapies specific to the indication (e.g., prior platinum chemotherapy for SCLC/UCC, prior targeted agents for ALK/EGFR/ROS1 positive NSCLC, prior VEGF/TKI therapy in RCC). Answer these items and attach documentation showing prior systemic therapies and whether disease progressed on those agents.

Respond to indication-specific prior therapy questions on the form
Attach records confirming prior systemic therapies and progression status where applicable

Answering the formProviders mark Yes/No to TMB-H based on reported mutations per megabase in the test report

inv-20: PD-L1 (CPS >=1) — definition for PD-L1 positivity where used.

PD-L1 (CPS) definitionPD-L1 positivity may be indicated by combined positive score (CPS) on IHC; CPS >=1 is used where specified on the form

Tumor contextsCervical, ESCC, non-squamous NSCLC, gastric/GEJ, metastatic NSCLC subsequent therapy and other tumor branches query PD-L1 CPS

How to answerYou may answer Yes if there is an indication that CPS is greater than or equal to the stated threshold on IHC results

See chunks 18,19,22,23 for branching logic on first-line vs subsequent

Breast cancer, chordoma, chondrosarcoma, osteosarcoma, BTC, ovarian, pancreatic, thyroid and other solid tumors query TMB-H where MSI-H/dMMR is not present

DocumentationAttach test report showing mutations per megabase to support TMB-H selection

inv-25: PD-L1 (CPS) — CPS thresholds (>=1 and CPS >=10 where specified).

Primary CPS thresholdCPS >=1 is the PD-L1 positivity threshold used across multiple tumor branches (may be indicated from IHC results)

Higher CPS threshold useFor certain breast (triple negative) questions the form uses CPS >=10 to define PD-L1 positive TNBC

How to reportYou may answer Yes if IHC indicates the CPS meets or exceeds the specified threshold (e.g., >=1 or >=10 where asked)

inv-26: PD-L1 — CPS >=1 (additional PD-L1 references across tumor branches).

PD-L1 CPS >=1 fieldIs your patient's cancer expressing PD-L1? (You may answer yes if CPS >=1 on IHC results)

Applicable branchesUsed for cervical, ESCC, non-squamous and squamous NSCLC branches, metastatic NSCLC subsequent therapy, and other tumor-specific questions

Response implicationPositive PD-L1 (CPS >=1) guides eligibility assessment and further branching on genetic testing and stage

inv-27: ALK testing requirement/field (NSCLC and related branches).

ALK testing fieldForm asks tumor genetic status: ALK-negative vs ALK-positive in NSCLC branches (first-line and subsequent); selectable options include ALK-negative, ALK-positive, or unknown/genetic testing not done

Branch implicationsALK status affects eligibility and follow-up questions regarding stage, prior therapies, and combination regimens

Related prior therapy questionsIf ALK-positive, form asks whether patient previously received ALK inhibitors (e.g., alectinib, ceritinib, crizotinib) in subsequent therapy branch

inv-28: EGFR testing requirement/field (NSCLC branches).

EGFR testing fieldForm asks EGFR-positive vs EGFR-negative status in NSCLC branches with selectable options and 'unknown/genetic testing not done'

Prior therapy follow-upIf EGFR-positive, form asks whether patient previously received EGFR-targeted agents (afatinib, erlotinib, gefitinib, osimertinib) when relevant

Stage and treatment impactEGFR status is used with PD-L1 and ALK/ROS1 status to determine stage-specific eligibility and prior treatment requirements

inv-29: ROS1 testing requirement/field.

ROS1 testing fieldForm asks whether tumors are ROS1-positive, ROS1-negative, or unknown in NSCLC subsequent and first-line branches

Prior therapy follow-upIf ROS1-positive, follow-up asks whether patient previously received crizotinib

Integration with other markersROS1 status is captured alongside ALK and EGFR to guide eligibility and prior targeted therapy history

inv-30: MSI-H/dMMR (additional branch reference).

MSI-H/dMMR additional branchMSI-H/dMMR is asked in tumor-specific branches including BTC, thyroid, ovarian, pancreatic and others to determine single-agent vs combination use and eligibility

Stage and prior therapy follow-upBranches ask whether MSI-H/dMMR patients have unresectable/metastatic disease, prior therapies, and progression status

Documentation must be attachedSupportive testing reports must be attached when MSI-H/dMMR is indicated on tumor branches

inv-31: TMB-H (additional branch reference).

TMB-H additional branch referencesTMB-H is queried for BTC, ovarian, pancreatic, thyroid and other tumor branches when MSI-H/dMMR is not present

Tumor-specific useForm asks whether TMB-H disease is present for these tumors and whether medication will be single-agent or part of combination therapy

Documentation requirementAttach laboratory or sequencing report showing mutations per megabase to support TMB-H selection

inv-32: del(17p)/TP53 testing requirement/field.

del(17p)/TP53 testing fieldFor CLL/SLL the form asks whether the patient has the del(17p)/TP53 mutation (Yes/No)

Clinical follow-upIf present, form further asks whether the patient is refractory to chemotherapy and unable to receive chemoimmunotherapy

Purposedel(17p)/TP53 status informs eligibility and selection of appropriate therapies for CLL/SLL branch