BlueCross BlueShield of Tennessee Medical Policy Manual

Pembrolizumab (Keytruda®)

NDC CODE(S)

00006-3026-XX KEYTRUDA 100 MG/4ML Solution (MERCK SHARP & DOHME)

DESCRIPTION

Pembrolizumab is a human programmed death receptor (PD-1)-blocking humanized monoclonal antibody.  It blocks the interaction between PD-1 and its ligands, PD-L1 and PD-L2 by binding to the PD-1 receptor which is found on T-cells.  This releases PD-1 pathway-mediated inhibition of the immune response, including the anti-tumor immune response, which results in decreased tumor growth.

POLICY

·         Pembrolizumab for the treatment of the following is considered medically necessary if the medical appropriateness criteria are met: (See Medical Appropriateness below.)

·         Pembrolizumab for the treatment of other conditions/diseases is considered investigational.

MEDICAL APPROPRIATENESS

INITIAL APPROVAL CRITERIA

·         Patient is at least 18 years of age (unless otherwise specified); AND

Universal Criteria

·         Patient has not received previous therapy with a programmed death (PD-1/PD-L1)-directed therapy (e.g., cemiplimab, avelumab, nivolumab, atezolizumab, durvalumab, etc.) unless otherwise specified; AND

Cutaneous Melanoma

·         Used as first-line therapy as a single agent for unresectable or metastatic disease; OR

·         Used as subsequent therapy for unresectable or metastatic* disease after disease progression or maximum clinical benefit from BRAF targeted therapy; AND

§  Anti-PD-1 immunotherapy was not previously used; OR

§  Used as re-induction therapy in patients who experienced disease control (i.e., complete response, partial response, or stable disease with no residual toxicity) from prior anti-PD-1 immunotherapy but subsequently have disease progression/relapse > 3 months after treatment discontinuation; OR

§  Used after progression on single-agent anti-PD-1 immunotherapy and combination ipilimumab/anti-PD-1 immunotherapy not previously used; OR

§  Used as re-induction therapy in patients who experienced disease control (i.e., complete response, partial response, or stable disease with no residual toxicity) from prior combination ipilimumab/anti-PD-1 immunotherapy, but subsequently have disease progression/relapse > 3 months after treatment discontinuation; OR

·         Used as a single agent for adjuvant treatment; AND

*Metastatic disease includes stage III clinical satellite/in transit metastases or local satellite/in-transit recurrence in

patients with limited resectable and unresectable disease, unresectable nodal recurrence, and disseminated (unresectable) distant metastatic disease

Uveal Melanoma

·         Used as a single agent; AND

·         Patient has distant metastatic disease

Gastric Cancer

·         Patient has recurrent, unresectable (or is not a candidate for surgery) locally advanced, or metastatic disease; AND

§  Patient has adenocarcinoma histology; AND

§  Tumor expresses PD-L1 (Combined Positive Score [CPS] ≥1) as determined by an FDA-approved or CLIA compliant test ❖; AND

§  Patient progressed on or after at least two prior systemic treatments

Esophageal Cancer or Gastroesophageal Junction Cancer

·         Used in combination with platinum- and fluoropyrimidine-based chemotherapy: AND

·         Used as a single agent; AND

§  Patient has squamous cell carcinoma; AND

Ø  Tumor expresses PD-L1 (CPS ≥ 10) as determined by an FDA-approved or CLIAcompliant test❖; AND

Ø  Patient progressed on or after at least one prior systemic treatment; OR

§  Patient has adenocarcinoma; AND

Ø  Tumor expresses PD-L1 (CPS ≥ 1) as determined by an FDA-approved or CLIA compliant test❖; AND

Ø  Used as palliative third-line or subsequent therapy

Merkel Cell Carcinoma (MCC)

·         Patient is at least 2 years of age; AND

·         Used as a single agent; AND

Non-Small Cell Lung Cancer (NSCLC)

·         Used for stage III disease; AND

·         Used for recurrent, advanced, or metastatic disease (excluding locoregional recurrence or symptomatic local disease without evidence of disseminated disease) or mediastinal lymph node recurrence with prior radiation therapy; AND

§  Used for one of the following:

Ø     PD-L1 expression-positive (TPS ≥1%) tumors, as detected by an FDA or CLIA compliant test❖ that are EGFR, ALK, ROS1, BRAF, NTRK1/2/3 gene fusion, MET exon 14 skipping mutation, and RET rearrangement negative*

Ø     Patients with performance status (PS) 0-1 who have EGFR, ALK, ROS1, BRAF, NTRK1/2/3 gene fusion, MET exon 14 skipping mutation, and RET rearrangement negative* tumors and PD-L1 expression <1%

Ø     Patients with PS 0-1 who are positive for one of the following molecular biomarkers: BRAF V600E mutation, NTRK1/2/3 gene fusion, MET exon 14 skipping mutation, or RET rearrangements; AND

§  Used in combination with pemetrexed AND either carboplatin or cisplatin for non-squamous cell histology; OR

§  Used in combination with carboplatin AND either paclitaxel or albumin-bound paclitaxel for squamous cell histology; OR

§  Used as single agent therapy (for PD-L1 expression-positive tumors ONLY); OR

§  Used in patients with tumors expressing PD-L1 (TPS ≥1%) as determined by an FDA-approved or CLIA compliant test ❖; AND

§  Used as single agent therapy; OR

§  Used for one of the following:

Ø     Patients with PS 0-1 who have EGFR, ALK, or ROS1 positive tumors and prior targeted therapy§

Ø     Patients with PS 0-1 who are positive for one of the following molecular    biomarkers: BRAF V600E mutations, NTRK1/2/3 gene fusions, MET exon 14 skipping mutation or RET rearrangements; AND

ù  Used in combination with carboplatin AND either paclitaxel or albumin-bound paclitaxel for squamous cell histology; OR

ù  Used in combination with pemetrexed AND either carboplatin or cisplatin for non-squamous cell histology; OR

§  Used in combination with pemetrexed following a first-line pembrolizumab/pemetrexed/(carboplatin or cisplatin) regimen for disease of nonsquamous cell histology; OR

§  Used as a single agent following a first-line pembrolizumab/carboplatin/(paclitaxel or nab-paclitaxel) regimen for disease of squamous cell histology; OR

§  Used as a single agent following a first-line pembrolizumab monotherapy regimen

 

* Note: If there is insufficient issue to allow testing for all of EGFR, ALK, ROS1, BRAF, NTRK1/2/3, MET and RET, repeat biopsy and/or plasma testing should be done. If these are not feasible, treatment is guided by available results and, if unknown, these patients are treated as though they do not have driver oncogenes.

Squamous Cell Carcinoma of the Head and Neck (SCCHN)

·         Patient has unresectable, recurrent/persistent, or metastatic disease; AND

§  Used as a single-agent for tumors expressing PD-L1 (CPS ≥1) as determined by an FDA-approved or CLIA-compliant test ❖; OR

§  Used in combination with fluorouracil and a platinum chemotherapy agent; OR

§  Used as a single-agent therapy for disease that has progressed on or after platinum-containing chemotherapy; OR

§  Used in combination with fluorouracil and a platinum chemotherapy agent in patients with non-nasopharyngeal disease and performance status 0-1

Adult Classical Hodgkin Lymphoma (cHL)

·         Used as a single agent for relapsed or refractory disease

Pediatric Classical Hodgkin Lymphoma

·         Patient is at least 2 years of age*; AND

·         Used as a single agent; AND

* Pediatric Classical Hodgkin Lymphoma may be applicable to adolescent and young adult (AYA) patients up to the age of 39 years.

Primary Mediastinal Large B-Cell Lymphoma (PMBCL)

·         Patient is at least 2 years of age; AND

·         Used as single agent; AND

·         Patient has relapsed or refractory disease; AND

·         Patient does not require urgent cytoreductive therapy

Urothelial Carcinoma (Bladder Cancer)

·         Patient has Bacillus Calmette-Guerin (BCG)-unresponsive, high-risk, non-muscle invasive bladder cancer (NMIBC) defined as one of the following:

* Adequate BCG therapy is defined as administration of at least five of six doses of an initial induction course AND

at least two of three doses of maintenance therapy or at least two of six doses of a second induction course

- OR -

·         Used as a single agent; AND

·         Patient has one of the following diagnoses:

§  Used for metastatic or recurrent disease (excluding recurrence of stage T3-4 disease

§  or palpable inguinal lymph nodes); OR

§  Used for clinical stage T3-4, cN1-2 disease, or cN1-2 palpable inguinal lymph nodes (first-line therapy only); AND

·         Used as subsequent therapy after previous platinum treatment*; OR

·         Used as first-line therapy in cisplatin-ineligible patients*; AND

* Note:

·         If platinum treatment occurred greater than 12 months ago, the patient should be re-treated with platinum-based therapy if the patient is still platinum eligible (see below for cisplatin- or carboplatin-ineligible comorbidities).

o    Cisplatin-ineligible comorbidities may include the following: GFR < 60 mL/min, PS ≥ 2, hearing loss of ≥ 25 decibels (dB) at two contiguous frequencies, or grades ≥ 2 peripheral neuropathy. Carboplatin may be substituted for cisplatin particularly in those patients with a GFR <60 mL/min or a PS of 2.

o    Carboplatin-ineligible comorbidities may include the following: GFR < 30 mL/min, PS ≥ 3, grade ≥ 3 peripheral neuropathy, or NYHA class ≥ 3, etc.

Cervical Cancer

·         Used as a single agent: AND

·         Patient has persistent, recurrent, or metastatic disease; AND

·         Tumor expresses PD-L1 (e.g., CPS ≥1) as determined by an FDA-approved or CLIA-compliant test❖; AND

·         Disease has progressed on or after chemotherapy

Microsatellite Instability-High (MSI-H) Cancer

·         Patient must be at least 2 years of age; AND

·         Used as a single agent; AND

·         Patient’s disease must be microsatellite instability-high (MSI-H) or mismatch repair

·         deficient (dMMR); AND

·         Pediatric patients must not have a diagnosis of MSI-H central nervous system cancer; AND

·         Patient has one of the following cancers:

 

§  Used as first-line therapy for unresectable (or medically inoperable) or metastatic disease; OR

§  Used as primary treatment for resectable liver and/or lung metastases (Rectal Cancer only); OR

§  Used as neoadjuvant therapy for resectable liver and/or lung metastases (Colon Cancer only); OR

§  Used for unresectable metastases that remain unresectable after primary systemic therapy; OR

§  Used for disease progression on non-intensive therapy with improvement in functional status (excluding patients previously treated with fluoropyrimidine); OR

§  Used for unresectable, advanced, or metastatic disease that has progressed following treatment with a fluoropyrimidine, oxaliplatin, and/or irinotecan

 

§  Used as subsequent therapy for locally advanced or metastatic disease after progression; OR

§  Used for recurrent or metastatic disease after resection; OR

§  Used as first-line therapy for metastatic disease for in patients with poor performance status (i.e., ECOG ≥2)

 

§  Used for unresectable or metastatic disease that has progressed following prior treatment; AND

§  Patient has no satisfactory alternative treatment options

 

§  Used as subsequent therapy for unresectable (or not a candidate for surgery) locally advanced, recurrent, or metastatic disease

 

§  Patient has carcinosarcoma, clear cell, endometrioid, mucinous, or serous histology; AND

§  Used for patients with persistent or recurrent disease; AND

§  Patient is not experiencing an immediate biochemical relapse (i.e., rising CA-125 with no radiographic evidence of disease)

 

§  Patient has recurrent, metastatic, or high-risk disease that has progressed following prior treatment

 

§  Used as subsequent treatment of unresectable or metastatic disease that has progressed following prior treatment; AND

§  Patient has no satisfactory alternative treatment options

 

§  Used as third-line therapy

§  Used as primary treatment for unresectable or metastatic disease; OR

§  Used for unresectable or metastatic disease that has progressed following prior treatment

 

§  Used for advanced, recurrent, or metastatic disease as second-line therapy

 

§  Used as second-line therapy for persistent, recurrent, or metastatic disease

 

§  Used for advanced or metastatic disease

 

§  Used for recurrent, metastatic, or unresectable disease that has progressed following prior treatment; AND

§  Patient has no satisfactory alternative treatment options

 

§  Used in symptomatic patients with PS 1-2 OR asymptomatic patients with PS 0 and aggressive disease; AND

§  Patient has adenocarcinoma or carcinoma not otherwise specified; AND

§  Patient has one of the following:

Ø  Axillary involvement in men if clinically indicated

Ø  Lung nodules or breast marker-negative pleural effusion

Ø  Resectable liver disease

Ø  Peritoneal mass or ascites with non-ovarian histology

Ø  Retroperitoneal mass of non-germ cell histology in selected patients

Ø  Unresectable liver disease or disseminated metastases

 

§  Patient has non-nasopharyngeal cancer

 

§  Patient has castration-resistant metastatic disease; AND

§  Patient will continue androgen deprivation therapy (ADT); AND

§  Patient previously received docetaxel or novel hormone therapy; OR

§  Patient previously received docetaxel and novel hormone therapy; AND

ù  Patient does not have visceral metastases

 

§  Used for unresectable or metastatic disease that progressed following prior treatment; AND

§  Patient has no satisfactory alternative treatment options

Vulvar Squamous Cell Carcinoma

·         Used as a single agent; AND

·         Patient has advanced, recurrent, or metastatic disease; AND

·         Tumor expresses PD-L1 (CPS ≥1) as determined by an FDA-approved or CLIA-compliant test❖; AND

·         Used as second-line therapy for disease progression on or after chemotherapy

Thymic Carcinoma

·         Used as a single agent; AND

Malignant Pleural Mesothelioma

·         Used as subsequent therapy as a single agent

Central Nervous System (CNS) Cancer

·         Used as single agent therapy; AND

·         Primary tumor is due to melanoma or PD-L1 positive non-small cell lung cancer (NSCLC); AND

T-Cell Lymphoma/Extranodal NK

·         Patient has relapsed or refractory nasal type disease; AND

·         Disease progressed following additional treatment with an alternative asparaginase-based chemotherapy regimen not previously used; AND

·         Participation in a clinical trial is unavailable

Anal Carcinoma

·         Patient has metastatic squamous cell disease; AND

·         Used as a single agent for subsequent therapy

Gestational Trophoblastic Neoplasia

·         Used as single-agent therapy for multiagent chemotherapy-resistant disease; AND

§  Patient has recurrent or progressive disease; AND

§  Patient was previously treated with a platinum/etoposide -containing regimen; OR

Hepatocellular Carcinoma (HCC)

·         Used as a single agent; AND

·         Patient progressed on or was intolerant to sorafenib; AND

·         Patient has Child-Pugh Class A liver impairment (i.e., excluding Child-Pugh Class B and C)

Mycosis Fungoides/Sezary Syndrome

·         Used as primary therapy OR for relapsed or persistent disease; AND

·         Used for disease refractory to multiple previous therapies

Renal Cell Carcinoma (RCC)

·         Patient has advanced, relapsed, or metastatic disease; AND

·         Patient has clear cell histology; AND

·         Used in combination with axitinib

Endometrial Carcinoma (Uterine Cancer)

·         Patient has advanced or recurrent disease; AND

·         Disease has progressed following prior systemic therapy; AND

·         Patient is not a candidate for curative surgery or radiation; AND

·         Used in combination with lenvatinib

Soft Tissue Sarcoma

·         Used as a single agent; AND

§  Used as subsequent therapy for advanced or metastatic disease

Tumor Mutational Burden-High (TMB-H) Cancer

·         Patient must be at least 2 years old; AND

·         Patient has solid tumors that are tumor mutational burden-high (TMB-H) [≥ 10 mutations/megabase (mut/Mb)] as determined by an FDA-approved or CLIA-compliant test❖; AND

·         Used as a single agent; AND

·         Pediatric patients must not have a diagnosis of TMB-H central nervous system cancer; AND

·         Patient has one of the following cancers:

 

§  Patient has unresectable or metastatic disease that progressed following prior treatment; AND

§  Patient has no satisfactory alternative treatment options

 

§  Patient has unresectable or metastatic disease that progressed following prior treatment; AND

§  Patient has no satisfactory alternative treatment options

 

§  Used as second-line therapy for unresectable or metastatic disease; AND

§  Patient has no satisfactory alternative treatment options

 

§  Used as subsequent therapy for unresectable (or not a candidate for surgery) locally advanced, recurrent, or metastatic disease

 

§  Used for recurrent metastatic disease in patients with a PS 0-3; OR

§  Used for unresectable locoregional recurrence or second primary with prior radiation therapy

 

§  Anaplastic Carcinoma

Ø  Patient has metastatic disease

§  Follicular Carcinoma, Papillary Carcinoma, Hürthle Cell Carcinoma

Ø  Used for unresectable recurrent, persistent, or metastatic disease not amenable to radioactive iodine (RAI)

§  Medullary Carcinoma

Ø   Patient has unresectable, recurrent, or persistent metastatic disease

 

§  Patient has unresectable or metastatic disease that progressed following prior treatment; AND

§  Patient has no satisfactory alternative treatment options

 

§  Used for advanced, recurrent, or metastatic disease as second-line therapy; AND

§  Patient has no satisfactory alternative treatment options

 

§  Used as third-line therapy

 

§  Used in symptomatic patients with PS 1-2 OR asymptomatic patients with PS 0 and aggressive disease; AND

Ø  Patient has squamous cell carcinoma; AND

ù  Patient has multiple lung nodules, pleural effusion, or disseminated metastases; OR

Ø  Patient has adenocarcinoma or carcinoma not otherwise specified; AND

ù  Patient has one of the following:

§  Axillary involvement in men if clinically indicated

§  Lung nodules or breast marker-negative pleural effusion

§  Resectable liver disease

§  Peritoneal mass or ascites with non-ovarian histology

§  Retroperitoneal mass of non-germ cell histology in selected patients

§  Unresectable liver disease or disseminated metastases

 

§  Patient has unresectable or metastatic disease that progressed following prior treatment; AND

§  Patient has no satisfactory alternative treatment options

 

Cutaneous Squamous Cell Carcinoma (cSCC)

·         Used as a single agent; AND

·         Patient has locally advanced, inoperable, or not fully resectable, recurrent, or metastatic disease that is not curable by surgery or radiation

Adrenal Gland Tumors

·         Patient has metastatic adrenocortical carcinoma (ACC)

Triple Negative Breast Cancer (TNBC)

·         Used in combination with chemotherapy; AND

·         Patient has recurrent unresectable or metastatic disease; AND

·         Tumor expresses PD-L1 (CPS ≥10) as determined by an FDA-approved or CLIA-compliant test❖

❖If confirmed using an immunotherapy assay-http://www.fda.gov/companiondiagnostics

 

Genomic Aberration Targeted Therapies

(not all inclusive, refer to guidelines for appropriate use)

Sensitizing EGFR mutation-positive tumors

Afatinib

Dacomitinib

Erlotinib

Gefitinib

Osimertinib

 

ALK rearrangement-positive tumors

Alectinib

Brigatinib

Ceritinib

Crizotinib

Lorlatinib

 

ROS1 rearrangement-positive tumors

Ceritinib

Crizotinib

Entrectinib

 

BRAF V600E-mutation positive tumors

Dabrafenib±Trametinib

Vemurafenib

 

NTRK Gene Fusion positive tumors

Entrectinib

Larotrectinib

 

PD-L1 expression-positive tumors (≥1%)

Atezolizumab

Entrectinib

Pembrolizumab

 

MET Exon-14 skipping mutations

Capmatinib

Crizotinib

 

RET rearrangement-positive tumors

Cabozantinib

Selpercatinib

Vandetanib

 

RENEWAL CRITERIA

·         Patient continues to meet universal and other indication-specific relevant criteria identified in Initial Approval Criteria; AND

·         Disease response with treatment as defined by stabilization of disease or decrease in size of tumor or tumor spread; AND

·         Absence of unacceptable toxicity from the drug. Examples of unacceptable toxicity include: severe infusion reactions, severe immune-mediated adverse reactions (e.g., pneumonitis, hepatitis, colitis, endocrinopathies, nephritis and renal dysfunction, dermatologic adverse reactions/rashes, hypophysitis, thyroid disorders, etc.), hepatoxicity when used in combination with axitinib, etc.; AND

·         For the follow indications, patient has not exceeded a maximum of twenty-four (24) months of therapy:

Cutaneous Melanoma (adjuvant treatment)

·         Patient has not exceeded a maximum of twelve (12) months of therapy

Cutaneous Melanoma (subsequent treatment after prior anti-PD-1 immunotherapy)

·         Refer to Initial Approval Criteria

Continuation Maintenance Therapy for NSCLC

·         Refer to Initial Approval Criteria

DOSAGE/ADMINISTRATION

INDICATION

DOSE

NSCLC, HCC, SCCHN, Gastric, GEJ, Esophageal, Cervical, Bladder Cancer/ Urothelial Carcinoma, RCC, Endometrial Carcinoma (that is NOT MSI-H/dMMR), cSCC, & TNBC

200 mg intravenously every 3 weeks or 400 mg intravenously every 6 weeks up to a maximum of 24 months in patients without disease progression or unacceptable toxicity

 

*NMIBC treatment may continue up to a maximum of 24 months in patients without persistent or recurrent disease, disease progression, or unacceptable toxicity.

Thymic Carcinoma & Vulvar Carcinoma

200 mg intravenously every 3 weeks up to a maximum of 24 months in patients without disease progression or unacceptable toxicity

Cutaneous Melanoma

Single agent therapy (excluding adjuvant treatment):

200 mg intravenously every 3 weeks or 400 mg every 6 weeks

until disease progression or unacceptable toxicity

In combination with ipilimumab:

200 mg intravenously every 3 weeks up to a maximum of 24 months in patients without disease progression or unacceptable toxicity

Adjuvant treatment:

200 mg intravenously every 3 weeks or 400 mg every 6 weeks up to a maximum of 12 months in patients without disease recurrence or unacceptable toxicity

Uveal Melanoma

2 mg/kg intravenously every 3 weeks until up to a maximum of 24 months in patients without disease progression or unacceptable toxicity

CNS metastases

10 mg/kg intravenously every 2 weeks until progression or unacceptable toxicity

cHL, PMBCL, MCC, MSI-H/dMMR Cancer, TMB-H Cancer

Adults*:

200 mg intravenously every 3 weeks or 400 mg every 6 weeks

Pediatrics*:

2 mg/kg (up to 200 mg) intravenously every 21 days

*Up to a maximum of 24 months in patients without disease progression or unacceptable toxicity

MPM

10 mg/kg intravenously every 2 weeks for up to 24 months or until confirmed progression or unacceptable toxicity

NK/T-Cell Lymphoma

2 mg/kg intravenously every 3 weeks

MF/SS

2 mg/kg intravenously every 3 weeks up to a maximum of 24 months in patients without disease progression or unacceptable toxicity

Gestational Trophoblastic Tumor

200 mg intravenously every 3 weeks or 400 mg intravenously every 6 weeks

Soft Tissue Sarcoma & Adrenal Gland Tumors (NOT MSIH/dMMR)

200 mg intravenously every 3 weeks

Anal Carcinoma

200 mg intravenously every 3 weeks or 400 mg intravenously every 6 weeks or 2 mg/kg intravenously every 3 weeks, up to a maximum of 24 months in patients without disease progression or unacceptable toxicity

Dosing should be calculated using actual body weight and not flat dosing (as applicable) based on the following:

·         Standard dose 200 mg IV every 3 weeks for patients > 50 kg

·         Use 100 mg IV every 3 weeks for patients ≤ 50 kg

-OR-

·         Standard dose 400 mg IV every 6 weeks for patients weighing > 82.5 kg

·         Use 300 mg IV every 6 weeks for patients weighing between 56 to 82.5 kg

·         Use 200 mg IV every 6 weeks for patients weighing ≤ 55 kg

Note: This information is not meant to replace clinical decision making when initiating or modifying medication therapy and should only be used as a guide. Patient-specific variables should be taken into account.

LENGTH OF AUTHORIZATION

Coverage will be provided for six months and may be renewed (unless otherwise specified).

·         SCCHN, cHL, NSCLC, HCC, Bladder Cancer/Urothelial Carcinoma, MPM, MSIH/dMMR, PMBCL, Cervical, Anal, Vulvar, MCC, Mycosis Fungoides/Sezary Syndrome, RCC, Thymic, Esophageal, GEJ, Gastric, Uveal Melanoma, TMB-H Cancer, cSCC, Endometrial Carcinoma, TNBC and Cutaneous Melanoma (in combination with ipilimumab) can be authorized up to a maximum of twenty-four (24) months of therapy.

·         Adjuvant therapy in cutaneous melanoma can be authorized up to a maximum of twelve (12) months of therapy.

DOSING LIMITS

Max Units (per dose and over time) [HCPCS Unit]:

Indication

Billable Units (BU)

Per unit

time (days)

SCCHN, cHL, NSCLC, Melanoma, Urothelial, Gastric, Esophageal, GEJ, PMBCL, Cervical, Vulvar, MSI- H/dMMR, MCC, RCC, Thymic, HCC, Gestational Trophoblastic Tumor, Soft Tissue Sarcoma, TMB-H Cancer, cSCC, Endometrial Carcinoma (that is not MSI-H/dMMR), Adrenal Gland Tumors (that are not MSI-H/dMMR), & TNBC

 

200 BU

 

21 days

MPM & CNS metastases

1150 BU

14 days

Anal Carcinoma, NK/T-Cell Lymphoma, MF/SS, & Uveal Melanoma

250 BU

21 days

APPLICABLE TENNESSEE STATE MANDATE REQUIREMENTS

BlueCross BlueShield of Tennessee’s Medical Policy complies with Tennessee Code Annotated Section 56-7-2352 regarding coverage of off-label indications of Food and Drug Administration (FDA) approved drugs when the off-label use is recognized in one of the statutorily recognized standard reference compendia or in the published peer-reviewed medical literature.

IMPORTANT REMINDER

We develop Medical Policies to provide guidance to Members and Providers.  This Medical Policy relates only to the services or supplies described in it.  The existence of a Medical Policy is not an authorization, certification, explanation of benefits or a contract for the service (or supply) that is referenced in the Medical Policy.  For a determination of the benefits that a Member is entitled to receive under his or her health plan, the Member's health plan must be reviewed.  If there is a conflict between the Medical Policy and a health plan, the express terms of the health plan will govern.

ADDITIONAL INFORMATION  

For appropriate chemotherapy regimens, dosage information, contraindications, precautions, warnings, and monitoring information, please refer to one of the standard reference compendia (e.g., the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) published by the National Comprehensive Cancer Network®, Drugdex Evaluations of Micromedex Solutions at Truven Health, or The American Hospital Formulary Service Drug Information).

SOURCES

1.     Keytruda [package insert]. Whitehouse Station, NJ; Merck & Co, Inc; March 2021. Accessed March 2021.

2.     Referenced with permission from the NCCN Drugs & Biologics Compendium (NCCN Compendium®) pembrolizumab. National Comprehensive Cancer Network, 2021. The NCCN Compendium® is a derivative work of the NCCN Guidelines®. NATIONAL COMPREHENSIVE CANCER NETWORK®, NCCN®, and NCCN GUIDELINES® are trademarks owned by the National Comprehensive Cancer Network, Inc. To view the most recent and complete version of the Compendium, go online to NCCN.org. Accessed March 2021.

3.     Alley EW, Lopez J, Santoro A, et al. Clinical safety and activity of pembrolizumab in patients with malignant pleural mesothelioma (KEYNOTE-028): preliminary results from a non-randomised, open-label, phase 1b trial. Lancet Oncol. 2017 May;18(5):623-630.

4.     Ott PA, Bang YJ, Berton-Rigaud D, et al. Safety and Antitumor Activity of Pembrolizumab in Advanced Programmed Death Ligand 1-Positive Endometrial Cancer: Results From the KEYNOTE-028 Study. J Clin Oncol. 2017 Aug 1;35(22):2535-2541.

5.     Ott PA, Piha-Paul SA, Munster P, et al. Safety and antitumor activity of the anti-PD-1 antibody pembrolizumab in patients with recurrent carcinoma of the anal canal. Ann Oncol. 2017 May 1;28(5):1036-1041. Doi: 10.1093/annonc/mdx029.

6.     Zinzani PL, Ribrag V, Moskowitz CH, et al. Safety and tolerability of pembrolizumab in patients with relapsed/refractory primary mediastinal large B-cell lymphoma. Blood. 2017 Jul 20;130(3):267-270. Doi: 10.1182/blood-2016-12-758383. Epub 2017 May 10.

7.     U.S. Food and Drug Administrations (FDA). Division of Drug Information. Health Alert. http://s2027422842.t.en25.com/e/es?s=2027422842&e=88882&elqTrackId=B1F0B909CCF90C71B9C490C37BFE6647&elq=3f0714083e82421a8af346a664bedbfb&elqaid=3588&elqat=1. Accessed May 2018

8.     Balar AV, Castellano D, O’Donnell PH, et al. First-line pembrolizumab in cisplatin-ineligible patients with locally advanced and unresectable or metastatic urothelial cancer (KEYNOTE-052): a multicenter, single-arm, phase 2 study. Lancet Oncol 2017; 18: 1483–92.

9.     Referenced with permission from the NCCN Drugs & Biologics Compendium (NCCN Compendium®) Merkel Cell Carcinoma. Version 1.2020. National Comprehensive Cancer Network, 20201. The NCCN Compendium® is a derivative work of the NCCN Guidelines®. NATIONAL COMPREHENSIVE CANCER NETWORK®, NCCN®, and NCCN GUIDELINES® are trademarks owned by the National Comprehensive Cancer Network, Inc. To view the most recent and complete version of the Compendium, go online to NCCN.org. Accessed January 2021.

10.  Referenced with permission from the NCCN Drugs & Biologics Compendium (NCCN Compendium®) Bladder Cancer. Version 6.2020. National Comprehensive Cancer Network, 20201. The NCCN Compendium® is a derivative work of the NCCN Guidelines®. NATIONAL COMPREHENSIVE CANCER NETWORK®, NCCN®, and NCCN GUIDELINES® are trademarks owned by the National Comprehensive Cancer Network, Inc. To view the most recent and complete version of the Compendium, go online to NCCN.org. Accessed January 2021.

11.  Referenced with permission from the NCCN Drugs & Biologics Compendium (NCCN Compendium®) Non-Small Cell Lung Cancer. Version 82.20201. National Comprehensive Cancer Network, 20201. The NCCN Compendium® is a derivative work of the NCCN Guidelines®. NATIONAL COMPREHENSIVE CANCER NETWORK®, NCCN®, and NCCN GUIDELINES® are trademarks owned by the National Comprehensive Cancer Network, Inc. To view the most recent and complete version of the Compendium, go online to NCCN.org. Accessed January 2021.

12.  Ghori E, Kaur B, Fisher RA, et al. Pembrolizumab is effective for drug-resistant gestational trophoblastic neoplasia. Lancet. 2017 Nov 25;390(10110):2343-2345.

13.  Chung HC, Lopez-Martin JA, Kao S, et al. Phase 2 study of pembrolizumab in advanced small-cell lung cancer (SCLC): KEYNOTE-158. J Clin Oncol 2018;36: Abstract 8506

14.  National Institutes of Health. Study of Pembrolizumab (MK-3475) Versus Placebo After Complete Resection of High-Risk Stage III Melanoma (MK-3475-054/KEYNOTE-054). Available at: http://clinicaltrials.gov/show/NCT02362594.

15.  Khodadoust M, Rook AH, Porcu P, et al. Pembrolizumab in Relapsed and Refractory Mycosis Fungoides and Sézary Syndrome: A Multicenter Phase II Study. J Clin Oncol. 2020 Jan 1;38(1):20-28. Doi: 10.1200/JCO.19.01056. Epub 2019 Sep 18.

16.  Giaccone, G, Kim C, Thompson J, et al. Pembrolizumab in patients with thymic carcinoma: a single-arm, single-centre, phase 2 study. Lancet. Volume 19, ISSUE 3, P347-355, March 01, 2018.

17.  Cho J, Kim HS, Ku BM, et al. Pembrolizumab for Patients With Refractory or Relapsed Thymic Epithelial Tumor: An Open-Label Phase II Trial. J Clin Oncol. 2018 Jun 15:JCO2017773184. Doi: 10.1200/JCO.2017.77.3184. [Epub ahead of print]

18.  Gupta S, Sonpavde G, Grivas P, et al. Defining “platinum-ineligible” patients with metastatic urothelial cancer (mUC). J Clin Oncol. 2019 Mar 1;37(7_suppl):451.

19.  Fahrenbruch R, Kintzel P, Bott AM, et al. Dose Rounding of Biologic and Cytotoxic Anticancer Agents: A Position Statement of the Hematology/Oncology Pharmacy Association. J Oncol Pract. 2018 Mar;14(3):e130-e136.

20.  Hematology/Oncology Pharmacy Association (2019). Intravenous Cancer Drug Waste Issue Brief. Retrieved from http://www.hoparx.org/images/hopa/advocacy/Issue-Briefs/Drug_Waste_2019.pdf

21.  Bach PB, Conti RM, Muller RJ, et al. Overspending driven by oversized single dose vials of cancer drugs. BMJ. 2016 Feb 29;352:i788.

22.  Schachter J, Ribas A, Long GV, et al. Pembrolizumab versus ipilimumab for advanced melanoma: final overall survival results of a multicentre, randomised, open-label phase 3 study (KEYNOTE-006). Lancet. 2017 Oct 21;390(10105):1853-1862. Doi: 10.1016/S0140-6736(17)31601-X. Epub 2017 Aug 16.

23.  Ribas A, Puzanov I, Dummer R, et al. Pembrolizumab versus investigator-choice chemotherapy for ipilimumab-refractory melanoma (KEYNOTE-002): a randomised, controlled, phase 2 trial. Lancet Oncol. 2015 Aug;16(8):908-18. Doi: 10.1016/S1470- 2045(15)00083-2. Epub 2015 Jun 23.

24.  Eggermont AMM, Blank CU, Mandala M, et al. Adjuvant Pembrolizumab versus Placebo in Resected Stage III Melanoma. N Engl J Med. 2018 May 10;378(19):1789-1801. Doi: 10.1056/NEJMoa1802357. Epub 2018 Apr 15.

25.  Gandhi L, Rodríguez-Abreu D, Gadgeel S, et al. Pembrolizumab plus Chemotherapy in Metastatic Non-Small-Cell Lung Cancer. N Engl J Med. 2018 May 31;378(22):2078-2092. Doi: 10.1056/NEJMoa1801005. Epub 2018 Apr 16.

26.  Paz-Ares L, Luft A, Vicente D, et al. Pembrolizumab plus Chemotherapy for Squamous Non-Small-Cell Lung Cancer. N Engl J Med. 2018 Nov 22;379(21):2040-2051. Doi: 10.1056/NEJMoa1810865. Epub 2018 Sep 25.

27.  Mok TSK, Wu YL, Kudaba I, et al. Pembrolizumab versus chemotherapy for previously untreated, PD-L1-expressing, locally advanced or metastatic non-small-cell lung cancer (KEYNOTE-042): a randomised, open-label, controlled, phase 3 trial. Lancet. 2019 May 4;393(10183):1819-1830. Doi: 10.1016/S0140-6736(18)32409-7. Epub 2019 Apr 4.

28.  Reck M, Rodríguez-Abreu D, Robinson AG, et al. Pembrolizumab versus Chemotherapy for PD-L1-Positive Non-Small-Cell Lung Cancer. N Engl J Med. 2016 Nov 10;375(19):1823-1833. Epub 2016 Oct 8.

29.  Herbst RS, Baas P, Kim DW, et al. Pembrolizumab versus docetaxel for previously treated, PD-L1-positive, advanced non-small-cell lung cancer (KEYNOTE-010): a randomised controlled trial. Lancet. 2016 Apr 9;387(10027):1540-1550. Doi: 10.1016/S0140-6736(15)01281-7. Epub 2015 Dec 19.

30.  Ott PA, Elez E, Hiret S, et al. Pembrolizumab in Patients With Extensive-Stage Small-Cell Lung Cancer: Results From the Phase Ib KEYNOTE-028 Study. J Clin Oncol. 2017 Dec 1;35(34):3823-3829. Doi: 10.1200/JCO.2017.72.5069. Epub 2017 Aug 16.

31.  Burtness B, Harrington KJ, Greil R, et al. Pembrolizumab alone or with chemotherapy versus cetuximab with chemotherapy for recurrent or metastatic squamous cell carcinoma of the head and neck (KEYNOTE-048): a randomised, open-label, phase 3 study. Lancet. 2019 Nov 23;394(10212):1915-1928. Doi: 10.1016/S0140-6736(19)32591-7. Epub 2019 Nov 1.

32.  Chow LQM, Haddad R, Gupta S, et al. Antitumor Activity of Pembrolizumab in Biomarker-Unselected Patients With Recurrent and/or Metastatic Head and Neck Squamous Cell Carcinoma: Results From the Phase Ib KEYNOTE-012 Expansion Cohort. Antitumor Activity of Pembrolizumab in Biomarker-Unselected Patients With Recurrent and/or Metastatic Head and Neck Squamous Cell Carcinoma: Results From the Phase Ib KEYNOTE-012 Expansion Cohort.

33.  Chen R, Zinzani PL, Fanale MA, et al. Phase II Study of the Efficacy and Safety of Pembrolizumab for Relapsed/Refractory Classic Hodgkin Lymphoma. J Clin Oncol. 2017 Jul 1;35(19):2125-2132. Doi: 10.1200/JCO.2016.72.1316. Epub 2017 Apr 25.

34.  Armand P, Rodig S, Melnichenko V, et al. Pembrolizumab in Relapsed or Refractory Primary Mediastinal Large B-Cell Lymphoma. J Clin Oncol. 2019 Dec 1;37(34):3291-3299. Doi: 10.1200/JCO.19.01389. Epub 2019 Oct 14.

35.  Powles T, Gschwend JE, Loriot Y, et al. Phase 3 KEYNOTE-361 trial: Pembrolizumab (pembro) with or without chemotherapy versus chemotherapy alone in advanced urothelial cancer. DOI: 10.1200/JCO.2017.35.15_suppl.TPS4590 Journal of Clinical Oncology 35, no. 15_suppl. Published online May 30, 2017.

36.  Bellmunt J, de Wit R, Vaughn DJ, et al. Pembrolizumab as Second-Line Therapy for Advanced Urothelial Carcinoma. N Engl J Med. 2017 Mar 16;376(11):1015-1026. Doi: 10.1056/NEJMoa1613683. Epub 2017 Feb 17.

37.  Balar AV, Kulkarni GS, Uchio, EM, et al. Keynote 057: Phase II trial of Pembrolizumab (pembro) for patients (pts) with high-risk (HR) nonmusical invasive bladder cancer (NMIBC) unresponsive to bacillus calmette-guérin (BCG). DOI: 10.1200/JCO.2019.37.7_suppl.350 Journal of Clinical Oncology 37, no. 7_suppl (March 01, 2019) 350-350. Published online February 26, 2019.

38.  Le DT, Kim TW, Van Cutsem E, et al. Phase II Open-Label Study of Pembrolizumab in Treatment-Refractory, Microsatellite Instability-High/Mismatch Repair-Deficient Metastatic Colorectal Cancer: KEYNOTE-164. J Clin Oncol. 2020 Jan 1;38(1):11-19. Doi: 10.1200/JCO.19.02107. Epub 2019 Nov 14.

39.  Fuchs CS, Doi T, Jang RW, et al. Safety and Efficacy of Pembrolizumab Monotherapy in Patients With Previously Treated Advanced Gastric and Gastroesophageal Junction Cancer: Phase 2 Clinical KEYNOTE-059 Trial. JAMA Oncol. 2018 May 10;4(5):e180013. Doi: 10.1001/jamaoncol.2018.0013. Epub 2018 May 10.

40.  Kojima T, Muro K, Francois E, et al. Pembrolizumab versus chemotherapy as second-line therapy for advanced esophageal cancer: Phase III KEYNOTE-181 study. DOI: 10.1200/JCO.2019.37.4_suppl.2 Journal of Clinical Oncology 37, no. 4_suppl (February 01, 2019) 2-2. Published online January 29, 2019.

41.  Shah M, Kojima T, Hochhauser D, et al. Efficacy and Safety of Pembrolizumab for Heavily Pretreated Patients With Advanced, Metastatic Adenocarcinoma or Squamous Cell Carcinoma of the Esophagus: The Phase 2 KEYNOTE-180 Study. JAMA Oncol . .550-546:)4(5;2019Doi:10.1001/jamaoncol.2018.5441.

42.  Chung HC, Ros W, Delord JP, et al. Efficacy and Safety of Pembrolizumab in Previously Treated Advanced Cervical Cancer: Results From the Phase II KEYNOTE-158 Study. J Clin Oncol. 2019 Jun 10;37(17):1470-1478. Doi: 10.1200/JCO.18.01265. Epub 2019 Apr 3.

43.  Zhu AX, Finn RS, Edeline J, et al. Pembrolizumab in patients with advanced hepatocellular carcinoma previously treated with sorafenib (KEYNOTE-224): a non-randomised, open label phase 2 trial. Lancet Oncol. 2018 Jul;19(7):940-952. Doi: 10.1016/S1470-2045(18)30351-6. Epub 2018 Jun 3.

44.  Nghiem P, Bhatia S, Lipson EJ, et al. Durable Tumor Regression and Overall Survival in Patients With Advanced Merkel Cell Carcinoma Receiving Pembrolizumab as First-Line Therapy. J Clin Oncol. 2019 Mar 20;37(9):693-702. Doi: 10.1200/JCO.18.01896. Epub 2019 Feb 6.

45.  Rini BI, Plimack ER, Stus V, et al. Pembrolizumab plus Axitinib versus Sunitinib for Advanced Renal-Cell Carcinoma. N Engl J Med. 2019 Mar 21;380(12):1116-1127. Doi: 10.1056/NEJMoa1816714. Epub 2019 Feb 16.

46.  Makker V, Taylor MH, Aghajanian C, et al. Lenvatinib (LEN) and pembrolizumab (PEMBRO) in advanced endometrial cancer (EC). Annals of Oncology, Volume 30, Issue Supplement_5, October 2019, MDZ250.002, https://doi.org/10.1093/annonc/mdz250.002.

47.  Goldberg SB, Gettinger SN, Mahajan A, et al. Pembrolizumab for patients with melanoma or non-small-cell lung cancer and untreated brain metastases: early analysis of a nonrandomized, open-label, phase 2 trial. Lancet Oncol. 2016 Jul;17(7):976-983. Doi: 10.1016/S1470-2045(16)30053-5. Epub 2016 Jun 3.

48.  Kwong YL, Chan TSY, Tan D, et al. PD1 blockade with pembrolizumab is highly effective in relapsed or refractory NK/T-cell lymphoma failing l-asparaginase. Blood. 2017 Apr 27;129(17):2437-2442. Doi: 10.1182/blood-2016-12-756841. Epub 2017 Feb 10.

49.  Referenced with permission from the NCCN Drugs & Biologics Compendium (NCCN Compendium®) Central Nervous System Cancers. Version 3.2020. National Comprehensive Cancer Network, 20201. The NCCN Compendium® is a derivative work of the NCCN Guidelines®. NATIONAL COMPREHENSIVE CANCER NETWORK®, NCCN®, and NCCN GUIDELINES® are trademarks owned by the National Comprehensive Cancer Network, Inc. To view the most recent and complete version of the Compendium, go online to NCCN.org. Accessed January 2021.

50.  Kluger HM, Chiang V, Mahajan A, et al. Long-Term Survival of Patients With Melanoma With Active Brain Metastases Treated With Pembrolizumab on a Phase II Trial. J Clin Oncol. 2019 Jan 1;37(1):52-60. doi: 10.1200/JCO.18.00204. Epub 2018 Nov 8.

51.  Marabelle A, Le DT, Ascierto PA, et al. Efficacy of Pembrolizumab in Patients With Noncolorectal High Microsatellite Instability/Mismatch Repair-Deficient Cancer: Results From the Phase II KEYNOTE-158 Study. J Clin Oncol. 2020 Jan 1;38(1):1-10. doi: 10.1200/JCO.19.02105. Epub 2019 Nov 4.

52.  Referenced with permission from the NCCN Drugs & Biologics Compendium (NCCN Compendium®) Anal Carcinoma. Version 2.2020. National Comprehensive Cancer Network, 20201. The NCCN Compendium® is a derivative work of the NCCN Guidelines®. NATIONAL COMPREHENSIVE CANCER NETWORK®, NCCN®, and NCCN GUIDELINES® are trademarks owned by the National Comprehensive Cancer Network, Inc. To view the most recent and complete version of the Compendium, go online to NCCN.org. Accessed January 2020.

53.  Kottschade LA, McWilliams RR, Markovic SN, et al. The Use of Pembrolizumab for the Treatment of Metastatic Uveal Melanoma. Melanoma Res. 2016 Jun;26(3):300-3. doi: 10.1097/CMR.0000000000000242.

54.  Algazi AP, Tsai KK, Shoushtari AN, et al. Clinical Outcomes in Metastatic Uveal Melanoma Treated With PD-1 and PD-L1 Antibodies. Cancer. 2016 Nov 15;122(21):3344-3353. doi: 10.1002/cncr.30258.

55.  Referenced with permission from the NCCN Drugs & Biologics Compendium (NCCN Compendium®) Gestational Trophoblastic Neoplasia. Version 3.2020. National Comprehensive Cancer Network, 20201. The NCCN Compendium® is a derivative work of the NCCN Guidelines®. NATIONAL COMPREHENSIVE CANCER NETWORK®, NCCN®, and NCCN GUIDELINES® are trademarks owned by the National Comprehensive Cancer Network, Inc. To view the most recent and complete version of the Compendium, go online to NCCN.org. Accessed January 2021.

56.  Burgess MA, Bolejack V, Van Tine BA, et al. Multicenter phase II study of pembrolizumab (P) in advanced soft tissue (STS) and bone sarcomas (BS): Final results of SARC028 and biomarker analyses. J Clin Oncol 2017; 35, no. 15_suppl (May 20, 2017) 11008-11008.

57.  Marabelle A, Fakih M, Lopez J, et al. Association of Tumor Mutational Burden with Outcomes in Patients with Select Advanced Solid Tumors Treated with Pembrolizumab in KEYNOTE-158. Ann Oncol. 2019;30(suppl_5):v475-v532. doi: 10.1093/annonc/mdz253.

58.  Grob J, Gonzalez Mendoza R, Basset-Seguin N, et al. Pembrolizumab for recurrent/metastatic cutaneous squamous cell carcinoma (cSCC): Efficacy and safety results from the phase II KEYNOTE-629 study. Ann Oncol. 2019;30(suppl_5):v908. doi: 10.1093/annonc/mdz394.069.

59.  Andre T, Shiu KK, Kim TW, et al. Pembrolizumab versus chemotherapy for microsatellite instability-high/mismatch repair deficient metastatic colorectal cancer: The phase 3 KEYNOTE-177 Study. J Clin Oncol. 2020;38(18_suppl):LBA4-LBA4.

60.  Geoerger B, Kang HJ, Yalon-Oren M, et al. Pembrolizumab in paediatric patients with advanced melanoma or a PD-L1-positive, advanced, relapsed, or refractory solid tumour or lymphoma (KEYNOTE-051): interim analysis of an open-label, single-arm, phase 1-2 trial. Lancet Oncol. 2020;21(1):121-133. doi:10.1016/S1470-2045(19)30671-0.

61.  Pembrolizumab Improves Progression-Free Survival in Relapsed/Refractory Hodgkin Lymphoma. Oncologist. 2020;25 Suppl 1(Suppl 1):S18-S19. doi:10.1634/theoncologist.2020-0561.

62.  Raj N, Zheng Y, Kelly V, et al. PD-1 Blockade in Advanced Adrenocortical Carcinoma. J Clin Oncol. 2020 Jan 1;38(1):71-80. doi: 10.1200/JCO.19.01586.

63.  Naing A, Meric-Bernstam F, Stephen B, et al. Phase 2 study of pembrolizumab in patients with advanced rare cancers [published correction appears in J Immunother Cancer. 2020 Apr;8(1):]. J Immunother Cancer. 2020;8(1):e000347. doi:10.1136/jitc-2019-000347.

64.  Crtes J, Cescon DW, Rugo HS, et al. KEYNOTE-355: Randomized, double-blind, phase III study of pembrolizumab + chemotherapy versus placebo + chemotherapy for previously untreated locally recurrent inoperable or metastatic triple-negative breast cancer. Journal of Clinical Oncology38, no. 15_suppl(May 20, 2020)1000-1000.

65.  Olson D, Luke JJ, Poklepovic AS, et al. Significant antitumor activity for low-dose ipilimumab (IPI) with pembrolizumab (PEMBRO) immediately following progression on PD1 Ab in melanoma (MEL) in a phase II trial. J Clin Oncol 2020;38(15_suppl): abstract 10004.

66.  Kato K, Shah MA, Enzinger P, et al. KEYNOTE-590: Phase III study of first-line chemotherapy with or without pembrolizumab for advanced esophageal cancer. Future Oncol. 2019 Apr;15(10):1057-1066. doi: 10.2217/fon-2018-0609.

67.  Lexicomp Online. (2021, February). AHFS DI. Pembrolizumab. Retrieved April 20, 2021 from Lexicomp Online with AHFS.

68.  MICROMEDEX Healthcare Series. Drugdex Evaluations. (2021, April). Pembrolizumab. Retrieved April 20, 2021.

ORIGINAL EFFECTIVE DATE:  12/1/2016

MOST RECENT REVIEW DATE:    8/31/2021

ID_MRx

Policies included in the Medical Policy Manual are not intended to certify coverage availability. They are medical determinations about a particular technology, service, drug, etc. While a policy or technology may be medically necessary, it could be excluded in a member's benefit plan. Please check with the appropriate claims department to determine if the service in question is a covered service under a particular benefit plan. Use of the Medical Policy Manual is not intended to replace independent medical judgment for treatment of individuals. The content on this Web site is not intended to be a substitute for professional medical advice in any way. Always seek the advice of your physician or other qualified health care provider if you have questions regarding a medical condition or treatment.

This document has been classified as public information