BlueCross BlueShield of Tennessee Medical Policy Manual

Pembrolizumab

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.)

• • Bladder Cancer/Urothelial Carcinoma

  • Central Nervous System Cancer

  • Gastric cancer

  • Hodgkin Lymphoma

  • Melanoma

  • Merkel cell carcinoma

  • Mesothelioma

  • Microsatellite Instability-High (MSI-H)/ Mismatch Repair Deficient (dMMR) Cancers

  • Non-small cell lung cancer (NSCLC)

  • Squamous Cell Carcinoma of the Head and Neck (SCCHN)

  • T-Cell Lymphoma/Extranodal NK

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

MEDICAL APPROPRIATENESS

INITIAL APPROVAL

• Pembrolizumab is considered medically appropriate if ALL of the following:

• • Individual is 18 years of age or older unless otherwise specified

  • Individual has not received previous therapy with a programmed death ligand (PD-1/PD-L1) -directed therapy (e.g., avelumab, nivolumab, atezolizumab, durvalumab, etc.) unless otherwise specified

  • Diagnosis of ANY ONE of the following:

  • • Anal cancer in second-line therapy as a single agent for metastatic disease

    • B-Cell lymphoma further diagnosed as relapsed or refractory primary mediastinal large B-cell lymphoma

    • Bladder Cancer/Urothelial Carcinoma if ANY ONE of the following:

    • • Used as first-line therapy in cisplatin-ineligible patients OR as subsequent therapy after previous platinum treatment in patients with a diagnosis of ANY ONE  of the following:

      • • Locally advanced or metastatic Urothelial Carcinoma

        • Disease recurrence post-cystectomy

        • Recurrent or metastatic Primary Carcinoma of the Urethra

      • Used as first-line therapy in cisplatin-ineligible patients in patients with a diagnosis of ANY ONE of the following:

      • • Metastatic Upper GU Tract Tumors

        • Metastatic Urothelial Carcinoma of the Prostate

    • Central Nervous System Cancer if used as a single agent for recurrent disease for brain metastases and pembrolizumab is active against the primary melanoma or NSCLC tumor

    • Gastric cancer if ALL of the following:

    • • Used as a single agent

      • Diagnosis of gastric or gastro-esophageal junction (GEJ) adenocarcinoma

      • Disease is recurrent, locally advanced or metastatic

      • Tumor expresses PD-L1 (CPS ≥1%) as determined by an FDA-approved test

      • Disease progression on or after minimum of two prior systemic treatments which must have included a fluoropyrimidine and platinum-containing regimen

      • Individuals with HER2 positive disease must have previously failed on HER2 directed therapy

    • Hodgkin lymphoma, diagnosed as classical Hodgkin lymphoma (cHL) for ALL of the following:

    • • Individual is 2 years of age or older

      • Disease is relapsed or refractory

      • Used as a single agent

      • Used after three or more prior lines of therapy in individuals less than 60 years old

    • Melanoma as a single agent, if disease is metastatic or unresectable (including re-induction treatment in individuals who experienced disease control, but subsequently disease progression/relapse > 3 months after treatment discontinuation)

    • Merkel cell carcinoma as a single agent for distant metastatic disease

    • Mesothelioma, Malignant Pleural if used as subsequent therapy as a single agent

    • Microsatellite Instability-High (MSI-H) or mismatch repair deficient (dMMR) Cancer if ALL of the following:

    • • Used as a single agent

      • Individual is 2 years of age or older

      • Disease must be microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR)

      • Pediatric individuals must NOT have a diagnosis of MSI-H central nervous system cancer

      • Disease is ANY ONE of the following:

      • • Bone Cancer (Ewing Sarcoma, Mesenchymal Chondrosarcoma, Osteosarcoma, Dedifferentiated Chondrosarcoma, or High-Grade Undifferentiated Pleomorphic Sarcoma)  Used for unresectable or metastatic disease after progression following prior treatment and individual has no satisfactory alternative treatment options

        • Colorectal Cancer for initial therapy in individuals with unresectable or metastatic disease who are not candidates for intensive therapy OR Used as primary treatment in patients with unresectable or metastatic disease who failed adjuvant treatment with FOLFOX (fluorouracil, leucovorin and oxaliplatin) or CapeOX (capecitabine-oxaliplatin) in the previous 12 months OR for unresectable or metastatic disease that has progressed following treatment with a fluoropyrimidine, oxaliplatin and irinotecan

        • Gastric adenocarcinoma OR esophageal/esophagogastric junction adenocarcinoma or squamous cell carcinoma  for Subsequent therapy for unresectable (or not a candidate for) locally advanced, recurrent, or metastatic disease

        • Ovarian Cancer/Fallopian Tube Cancer/Primary Peritoneal Cancer - Epithelial Ovarian Cancer/Fallopian Tube Cancer/Primary Peritoneal Cancer for persistent disease or recurrence

        • Pancreatic Adenocarcinoma for Second-line therapy for unresectable or metastatic disease after progression for patients with good performance status

        • Testicular Cancer for third-line therapy or after progression with high-dose chemotherapy

        • Uterine Cancer (Endometrial Carcinoma) for individuals with high risk tumors, or recurrent or metastatic disease, that have progressed following prior cytotoxic chemotherapy

        • Penile Cancer for subsequent treatment of unresectable or metastatic disease that is progressive and there are no other satisfactory treatment options

        • Other Solid Tumor for disease progression following prior treatment and there are no satisfactory alternative treatment options

    • Non-small cell lung cancer for ANY ONE of the following:

    • • Metastatic or recurrent disease with a tumor that has high PD-L1 expression (Tumor Proportion Score [TPS] ≥50%) as determined by an FDA-approved test as a single agent for first-line therapy for genomic tumor aberration (e.g., EGFR, ALK, ROS1 and BRAF) negative or unknown

      • Metastatic disease with tumor that  has PD-L1 expression  (TPS ≥1%) as determined by an FDA-approved test with ALL of the following:

      • • Used as a single agent

        • Disease progression on or after cytotoxic therapy

        • Individual with genomic tumor aberrations must have progressed following systemic therapy for those aberrations (e.g., EGFR, ALK, etc.)

      • Used in combination with pemetrexed and carboplatin for metastatic or recurrent disease of nonsquamous histology for ANY ONE of the following:

      • • First-line therapy for genomic tumor aberration (e.g., EGFR, ALK, ROS1 and, BRAF) negative or unknown, and PD-L1 expression <50% or unknown

        • First-line therapy for BRAF V600E-mutation positive tumors

        • Subsequent therapy for genomic tumor aberration (e.g., EGFR, BRAF V600E, ALK, and ROS1) positive and prior targeted therapy (See Targeted Therapies chart below)

        • Subsequent therapy if PD-L1 expression-positive (≥50%) and, for genomic tumor aberration (e.g., EGFR, ALK, ROS1 and BRAF) negative or unknown

    • Squamous cell carcinoma of the head and neck (SCCHN) if ALL of the following:

    • • Disease progression on or after platinum-containing chemotherapy

      • Used as a single agent

      • Disease is unresectable, recurrent, persistent or metastatic

    • T-Cell Lymphoma/Extranodal NK if ALL of the following:

    • • Individual has nasal type disease that is relapsed or refractory

      • Disease progressed following additional treatment with asparaginase-based chemotherapy, clinical trials or other best supportive care

RENEWAL CRITERIA

• Pembrolizumab is considered medically appropriate for renewal if ALL of the following criteria are met:

• • Individual continues to meet initial approval criteria

  • Tumor response as defined by lack of tumor progression, improvement in tumor size and/or improvement in symptoms

  • Absence of unacceptable toxicity from the agent, e.g., severe infusion reactions, immune-mediated adverse reactions such as pneumonitis, hepatitis, colitis, endocrinopathies, nephritis and renal dysfunction, skin reactions, etc.

  • For a diagnosis of ANY ONE of the following, the individual has not exceeded a maximum of twenty-four (24) months of therapy

  • • Classical Hodgkin Lymphoma (cHL)

    • Gastric/GEJ Adenocarcinoma

    • Malignant Pleural Mesothelioma

    • MSI-H/dMMR Cancer

    • Non-small cell lung cancer (NSCLC)

    • Squamous Cell Carcinoma of the Head and Neck (SCCHN)

    • Urothelial Carcinoma/Bladder Cancer

  • Melanoma Re-Induction (metastatic or unresectable disease) if ALL of the following:

  • • Individual with a performance status of 0-2 experienced disease control, but subsequent disease progression/relapse > 3 months after treatment discontinuation

LENGTH OF AUTHORIZATION

Coverage will be provided for six months and may be renewed.

SCCHN, cHL, NSCLC, Urothelial Carcinoma, MPM, MSI-H/dMMR & Gastric/GEJ Cancer can be authorized up to a maximum of 24 months of therapy.

Click here to view DOSAGE LIMITS

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).

No controlled studies were found in the published literature that validate the use of pembrolizumab for the treatment or prevention of other conditions or diseases.

SOURCES

Eastern Cooperative Oncology Group. (2015, May) ECOG Performance Status. Retrieved May 1, 2015 from http://ecog-acrin.org/resources/ecog-performance-status.

Lexicomp Online. (2018). AHFS DI. Pembrolizumab. Retrieved February 23, 2018 from Lexicomp Online with AHFS.

MICROMEDEX Healthcare Series. Drugdex Evaluations. (2017, December). Pembrolizumab. Retrieved February 23, 2018.

National Comprehensive Cancer Network. (2018). NCCN Drugs & Biologics Compendium®. Pembrolizumab. Retrieved February 23, 2018 from the National Comprehensive Cancer Network.

U. S. Food and Drug Administration. (2017, November). Center for Drug Evaluation and Research. Keytruda® (pembrolizumab) for injection. Retrieved February 23, 2018 from https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/125514s031lbl.pdf. 

ORIGINAL EFFECTIVE DATE:  9/18/2014

MOST RECENT REVIEW DATE:  5/8/2018

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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.