Notification



Notification Issue Date:



Medical Policy Bulletin


Title:Programmed Death Receptor-1 (PD-1) Antagonists (e.g., Keytruda®, Opdivo®) and Programmed Death-Ligand 1 (PD-L1) Antagonists (e.g., Tecentriq®, Bavencio®, Imfinzi™)

Policy #:08.01.20j

This policy is applicable to the Company’s commercial products only. Policies that are applicable to the Company’s Medicare Advantage products are accessible via a separate Medicare Advantage policy database.


The Company makes decisions on coverage based on Policy Bulletins, benefit plan documents, and the member’s medical history and condition. Benefits may vary based on contract, and individual member benefits must be verified. The Company determines medical necessity only if the benefit exists and no contract exclusions are applicable.

When services can be administered in various settings, the Company reserves the right to reimburse only those services that are furnished in the most appropriate and cost-effective setting that is appropriate to the member’s medical needs and condition. This decision is based on the member’s current medical condition and any required monitoring or additional services that may coincide with the delivery of this service.

This Medical Policy Bulletin document describes the status of medical technology at the time the document was developed. Since that time, new technology may have emerged or new medical literature may have been published. This Medical Policy Bulletin will be reviewed regularly and be updated as scientific and medical literature becomes available. For more information on how Medical Policy Bulletins are developed, go to the About This Site section of this Medical Policy Web site.



Policy

Coverage is subject to the terms, conditions, and limitations of the member's contract.

MEDICALLY NECESSARY

ATEZOLIZUMAB (TECENTRIQ®)
Urothelial Carcinoma

Atezolizumab (Tecentriq®) is considered medically necessary and, therefore, covered as single-agent therapy for the treatment of one of the following indications:
  • Locally advanced or metastatic urothelial carcinoma in individuals who:
    • have disease progression in one of the following scenarios:
      • during or following platinum-containing chemotherapy
      • within 12 months of neoadjuvant or adjuvant treatment
    • are not eligible for cisplatin-containing chemotherapy
  • As single agent therapy for clinical stage T4b or T2-T4a, N1-3 bladder cancer, for recurrence post-cystectomy, or for metastatic disease as subsequent systemic therapy or first-line therapy in cisplatin-ineligible individuals.
  • As subsequent systemic therapy, or first-line therapy in cisplatin-ineligible individuals for metastatic disease for one of the following conditions:
    • primary carcinoma of the urethra
    • upper genitourinary (GU) tract tumors
    • urothelial carcinoma of the prostate

Non-Small Cell Lung Cancer (NSCLC)

Atezolizumab (Tecentriq®) is considered medically necessary and, therefore, covered as a National Comprehensive Cancer Network (NCCN)--preferred single-agent therapy for the treatment of individuals with metastatic non-small cell lung cancer (NSCLC) when the individual meets all of the following criteria:
  • Eastern Cooperative Oncology Group (ECOG) performance status 0-2
  • Progression on or after a first-line platinum-based chemotherapy, or further progression on other systemic therapy
  • Other systemic immune checkpoint inhibitors (e.g., nivolumab [Opdivo®], pembrolizumab [Keytruda®], avelumab [Bavencio®], durvalumab (Imfinzi]) were not previously given
  • Disease progression on a US Food and Drug Administration (FDA)--approved therapy for EGFR or ALK genomic tumor aberrations, if individual has tested positive (e.g., afatinib [Gilotrif], alectinib [Alecensa], ceritinib [Zykadia®], crizotinib [Xalkori®], erlotinib [Tarceva®], gefitinib [Iressa®], osimertinib [Tagrisso®])

NIVOLUMAB (OPDIVO®)
Melanoma

Nivolumab (Opdivo®) is considered medically necessary and, therefore, covered as single-agent therapy or in combination with ipilimumab (Yervoy®) for the treatment of individuals with unresectable or metastatic melanoma in one of the following regimens:
  • First-line therapy
  • Second-line or subsequent therapy for disease progression for individuals with Eastern Cooperative Oncology Group (ECOG) performance status 0-2 if not previously used
  • After maximum clinical benefit from BRAF-targeted therapy for individuals with PS 0-2
  • Re-induction therapy for individuals with PS 0-2 who experience disease control and have no residual toxicity but experience progression/relapse more than 3 months after treatment discontinuation.

Non-Small Cell Lung Cancer (NSCLC)

Nivolumab (Opdivo®) is considered medically necessary and, therefore, covered as single-agent therapy for the treatment of individuals with metastatic non-small cell lung cancer (NSCLC) and ECOG 0-2 who had progression on or after platinum-based chemotherapy or other systemic therapy.
  • Prior to receiving nivolumab (Opdivo®), individuals with EGFR or ALK genomic tumor aberrations should have disease progression on a US Food and Drug Administration (FDA)--approved therapy (e.g., afatinib [Gilotrif], alectinib [Alecensa], ceritinib [Zykadia], crizotinib [Xalkori], erlotinib [Tarceva], gefitinib [Iressa], osimertinib [Tagrisso])

Renal Cell Carcinoma (RCC)

Nivolumab (Opdivo®) is considered medically necessary and, therefore, covered as single-agent therapy for the treatment of individuals with advanced renal cell carcinoma (RCC) who have received prior anti-angiogenic therapy (e.g., sorafenib [Nexavar®], sunitinib [Sutent®], bevacizumab [Avastin®], pazopanib [Votrient®], axitinib [Inlyta®]).

Classical Hodgkin's Lymphoma (cHL)

Nivolumab (Opdivo®) is considered medically necessary and, therefore, covered as single-agent therapy for:
  • the treatment of adult individuals with classical Hodgkin's lymphoma that have relapsed or progressed after either of the following:
    • autologous hematopoietic stem cell transplantation (HSCT) and brentuximab vedotin (Adcetris)
    • 3 or more lines of systemic therapy that includes autologous HSCT
  • additional therapy for refractory disease if Deauville 4-5 or relapsed disease in individuals previously treated with brentuximab vedotin (Adcetris)
  • palliative therapy for relapsed or refractory disease in older (age 60 and above) individuals

Head and Neck Squamous Cell Carcinoma (HNSCC)

Nivolumab (Opdivo®) is considered medically necessary and, therefore, covered as single-agent therapy for the treatment of:
  • recurrent or metastatic squamous cell carcinoma of the head and neck with disease progression on or after a platinum-based therapy
  • recurrent or metastatic non-nasopharyngeal squamous cell carcinoma of the head and neck with disease progression on or after a platinum-based therapy in:
    • newly diagnosed T4b, any N, M0 disease, unresectable nodal disease with no metastases, or individuals unfit for surgery and performance status (PS) 3
    • metastatic (M1) disease at initial presentation or recurrent/persistent disease with distant metastases, or unresectable locoregional recurrence or second primary with prior radiation therapy (RT) and PS 0-2
    • unresectable locoregional recurrence without prior RT and PS 3

Urothelial Carcinoma

Nivolumab (Opdivo®) is considered medically necessary and, therefore, covered as single-agent therapy for the treatment of one of the following indications:
  • locally advanced or metastatic urothelial carcinoma in individuals with disease progression, in one of the following scenarios:
    • during or following platinum-containing chemotherapy
    • within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy
  • A single agent therapy for clinical stage T4b or T2-T4a, N1-3 bladder cancer, for recurrence post cystectomy, or for metastatic disease as subsequent systemic therapy.
  • As subsequent systemic therapy for metastatic disease for one of the following conditions:
    • primary carcinoma of the urethra
    • upper genitourinary tract tumors
    • urothelial carcinoma of the prostate

Small Cell Lung Cancer

Nivolumab (Opdivo®) is considered medically necessary and, therefore, covered as single-agent or in combination with ipilimumab (Yervoy®), in individuals with performance status 0-2 therapy as subsequent systemic therapy for the treatment of primary progressive small cell lung cancer, or for relapse within 6 months following complete or partial response or stable disease with initial treatment.

Microsatellite Instability-High Cancer

Nivolumab (Opdivo®) is considered medically necessary and, therefore, covered as a single agent for one of the following:
  • treatment for individuals ages 12 years and older with unresectable advanced or metastatic colorectal cancer (MSI-H) following previous oxaliplatin-, irinotecan-, and/or fluoropyrimidine-based therapy
  • primary treatment for individuals with unresectable metachronous metastases (defective mismatch repair/high microsatellite instability only) that has progressed after previous adjuvant treatment with FOLFOX (fluorouracil, leucovorin, and oxaliplatin) or CAPEOX (capecitabine and oxaliplatin) within the last 12 months
  • initial treatment for individuals with unresectable advanced or metastatic colorectal cancer (MSI-H) who are not appropriate for intensive therapy

Malignant Pleural Mesothelioma

Nivolumab (Opdivo®) is considered medically necessary and, therefore, covered as a single agent or in combination with ipilimumab (Yervoy®), as subsequent systemic therapy for the treatment of malignant pleural mesothelioma.

PEMBROLIZUMAB (KEYTRUDA®)

Melanoma

Pembrolizumab (Keytruda®) is considered medically necessary and, therefore, covered as single-agent therapy for the treatment of individuals with unresectable or metastatic melanoma in one of the following regimens:
  • first-line therapy
  • second-line or subsequent therapy for disease progression for individuals with Eastern Cooperative Oncology Group (ECOG) performance status 0-2 if anti PD-1 monotherapy not previously used
  • after maximum clinical benefit from BRAF targeted therapy for individuals with PS 0-2
  • re-induction therapy for individuals with PS 0-2 who experience disease control and have no residual toxicity, but subsequently experience disease progression/relapse more than 3 months after treatment discontinuation

Non-Small Cell Lung Cancer (NSCLC)

Pembrolizumab (Keytruda®) is considered medically necessary and, therefore, covered as single-agent therapy for:
  • Treatment of individuals with ECOG 0-2 who have metastatic NSCLC with disease progression on or after platinum-containing chemotherapy or other systemic therapy. An FDA-approved test must confirm that that tumors express PD-L1.
    • Prior to receiving pembrolizumab (Keytruda®), individuals with EGFR or ALK genomic tumor aberrations should have disease progression on a US Food and Drug Administration (FDA)--approved therapy (e.g., afatinib [Gilotrif®], alectinib [Alecensa®], ceritinib [Zykadia®], crizotinib [Xalkori®], erlotinib [Tarceva®], gefitinib [Iressa®], osimertinib [Tagrisso®])
  • First-line therapy, in individuals who have tumors with high PD-L1 expression (Tumor Proportion Score ≥50%) as determined by an FDA-approved test, with no EGFR or ALK genomic tumor aberrations
  • Subsequent therapy for:
    • sensitizing EGFR mutation positive tumors and prior erlotinib (Tarceva®), afatinib (Gilotrif®), gefitinib (Iressa®), or osimertinib (Tagrisso®) therapy
    • ALK rearrangement-positive tumors and prior crizotinib (Xalkori®), certinib (Zykadia®), or alectinib (Alecensa®) therapy
    • ROS1 rearrangement-positive tumors and prior crizotinib (Xalkori®) therapy

Pembrolizumab (Keytruda®) is considered medically necessary and, therefore, covered as first-line therapy, when used in combination with pemetrexed and carboplatin, for the treatment of individuals with metastatic non-squamous NSCLC.

Head and Neck Squamous Cell Carcinoma (HNSCC)

Pembrolizumab (Keytruda®) is considered medically necessary and, therefore, covered as single-agent therapy for the treatment of recurrent or metastatic non-nasopharyngeal squamous cell carcinoma of the head and neck with disease progression on or after a platinum-based therapy in:
  • newly diagnosed T4b, any N, M0 disease, unresectable nodal disease with no metastases, or individuals unfit for surgery and performance status (PS) 3
  • metastatic (M1) disease at initial presentation or recurrent/persistent disease with distant metastases, or unresectable locoregional recurrence or second primary with prior radiation therapy (RT) and PS 0-2
  • unresectable locoregional recurrence without prior RT and PS 3

Classical Hodgkin Lymphoma (cHL)

Pembrolizumab (Keytruda®) is considered medically necessary and, therefore, covered as single-agent therapy for:
  • the treatment of adult and pediatric individuals with refractory cHL, or who have relapsed after 3 or more prior lines of therapy
  • additional therapy for refractory disease if Deauville 4-5 or relapsed disease in individuals previously treated with brentuximab vedotin (Adcetris)
  • palliative therapy for relapsed or refractory disease in older (age 60 and above) adults

Urothelial Carcinoma

Pembrolizumab (Keytruda®) is considered medically necessary and, therefore, covered as single-agent therapy for the treatment of one of the following indications:
  • locally advanced or metastatic urothelial carcinoma in individuals:
    • not eligible for cisplatin-containing chemotherapy
    • who have disease progression in one of the following scenarios:
      • during or following platinum-containing chemotherapy
      • within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy
  • A single agent therapy for clinical stage T4b or T2-T4a, N1-3 bladder cancer, for recurrence post cystectomy, or for metastatic disease as first-line therapy in cisplatin ineligible individuals, or as subsequent systemic therapy.
  • As first line therapy for metastatic disease in cisplatin ineligible individuals, or as subsequent systemic therapy for one of the following conditions:
    • primary carcinoma of the urethra
    • upper genitourinary tract tumors
    • urothelial carcinoma of the prostate

Microsatellite Instability-High Cancer

Pembrolizumab (Keytruda®) is considered medically necessary and, therefore, covered as single-agent therapy for the treatment of adult and pediatric individuals with unresectable or metastatic, microsatellite instability-high (MSI-H) or mismatch repair deficient:
  • solid tumors that have progressed following prior treatment and who have no satisfactory alternative treatment options
  • colorectal cancer that has progressed following treatment with fluoropyrimidine, oxaliplatin, and irinotecan
  • colorectal cancer with unresectable metachronous metastases that has progressed after previous adjuvant treatment with FOLFOX (fluorouracil, leucovorin, and oxaliplatin) or CAPEOX (capecitabine and oxaliplatin) within the last 12 months
Limitation of use: the safety and effectiveness of pembrolizumab (Keytruda®) in pediatric individuals with MSI-H central nervous system cancers have not been established.

Merkel Cell Carcinoma

Pembrolizumab (Keytruda®) is considered medically necessary and, therefore, covered as single-agent therapy for the treatment of distant metastatic merkel cell carcinoma or disseminated recurrence with or without surgery or radiation therapy.

Malignant Pleural Mesothelioma

Pembrolizumab (Keytruda®) is considered medically necessary and, therefore, covered as a single agent as subsequent systemic therapy for the treatment of malignant pleural mesothelioma.

AVELUMAB (BAVENCIO®)
Merkel Cell Carcinoma (MCC)

Avelumab (Bavencio®) is considered medically necessary and, therefore, covered in adult and pediatric individuals 12 years and older with metastatic Merkel cell carcinoma.

Urothelial Carcinoma

Avelumab (Bavencio®) is considered medically necessary and, therefore, covered as single-agent therapy for the treatment of one of the following indications:
  • Locally advanced or metastatic urothelial carcinoma in individuals with who have disease progression in one of the following scenarios:
    • during or following platinum-containing chemotherapy
    • within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy
  • A single agent therapy for clinical stage T4b or T2-T4a, N1-3 bladder cancer, for recurrence post cystectomy, or for metastatic disease as subsequent systemic therapy
  • As a single agent, subsequent systemic therapy for metastatic disease for one of the following conditions:
    • primary carcinoma of the urethra
    • upper genitourinary tract tumors
    • urothelial carcinoma of the prostate

DURVALUMAB (IMFINZI)
Urothelial Carcinoma

Durvalumab (Imfinzi) is considered medically necessary and, therefore, covered as single-agent therapy for the treatment of one of the following indications:
  • Locally advanced or metastatic urothelial carcinoma in individuals who have disease progression in one of the following scenarios:
    • during or following platinum-containing chemotherapy
    • within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy
  • A single agent therapy for clinical stage T4b or T2-T4a, N1-3 bladder cancer, for recurrence post cystectomy, or for metastatic disease as subsequent systemic therapy
  • As subsequent systemic therapy for metastatic disease for one of the following conditions:
    • primary carcinoma of the urethra
    • upper genitourinary tract tumors
    • urothelial carcinoma of the prostate

EXPERIMENTAL/INVESTIGATIONAL

All other uses for programmed death receptor-1 (PD-1) antagonists (e.g., Keytruda®, Opdivo®) and programmed death-ligand 1 (PD-L1) antagonists (e.g., Tecentriq®, Bavencio®, Imfinzi) are considered experimental/investigational and, therefore, not covered unless the indication is supported as an accepted off-label use, as defined in the Company medical policy on off-label coverage for prescription drugs and biologics.

REQUIRED DOCUMENTATION

The individual's medical record must reflect the medical necessity for the care provided. These medical records may include, but are not limited to: records from the professional provider's office, hospital, nursing home, home health agencies, therapies, and test reports.

The Company may conduct reviews and audits of services to our members, regardless of the participation status of the provider. All documentation is to be available to the Company upon request. Failure to produce the requested information may result in a denial for the drug.
Guidelines

BENEFIT APPLICATION

Subject to the terms and conditions of the applicable benefit contract, programmed death receptor-1 (PD-1) antagonists (e.g., Keytruda®, Opdivo®) and programmed death-ligand 1 (PD-L1) antagonist (e.g., Tecentriq®) are covered under the medical benefits of the Company’s products when the medical necessity criteria listed in this medical policy are met.

THE EASTERN COOPERATIVE ONCOLOGY GROUP (ECOG) PERFORMANCE STATUS

The Eastern Cooperative Oncology Group (ECOG), established in 1955, was one of the first groups to coordinate multicenter cancer clinical trials. The National Cancer Institute (NCI) is the primary funding source, and ECOG has evolved from a small consortium of institutions in the eastern United States to one of the largest clinical cancer research organizations in the country. As part of their work in the treatment of cancer, ECOG has developed the ECOG Performance Status (EPS), originally published in 1982 in the American Journal of Clinical Oncology. The use of the scales and the criteria in the EPS allows clinicians and researchers to determine an individual’s disease progression in terms of how the activities of daily living (ADL) are affected.
ECOG Performance Status
Grade
ECOG
0
Fully active, able to carry on all pre-disease performance without restriction
1
Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature (eg, light house work, office work)
2
Ambulatory and capable of all self care but unable to carry out any work activities. Up and about more than 50 percent of waking hours
3
Capable of only limited self care, confined to bed or chair more than 50 percent of waking hours
4
Completely disabled. Cannot carry on any self care: Totally confined to bed or chair
5
Dead
Oken MM, Creech RH, Tormey DC, et al. Toxicity and response criteria of the Eastern Cooperative Oncology Group. Am J Clin Oncol.1982;5(6):649-655.

TNM STAGING SYSTEM

According to the American Joint Committee on Cancer (AJCC), the TNM system is based on 3 key pieces of information:
  • T describes how far the main (primary) tumor has grown through the bladder wall and whether it has grown into nearby tissues.
  • N indicates any cancer spread to lymph nodes near the bladder. Lymph nodes are bean-sized collections of immune system cells, to which cancers often spread first.
  • M indicates whether or not the cancer has spread (metastasized) to distant sites, such as other organs or lymph nodes that are not near the bladder.

Numbers or letters appear after T, N, and M to provide more details about each of these factors. Higher numbers mean the cancer is more advanced.

American Cancer Society. Bladder cancer stages. Last Revised: 05/23/2016. Available at: http://www.cancer.org/cancer/bladdercancer/detailedguide/bladder-cancer-staging . Accessed January 3, 2017.

PET 5-POINT SCALE (DEAUVILLE CRITERIA)

The Deauville scale is a 5-point scoring system recommended internationally for staging and assessment of treatment response in Hodgkin's lymphoma and certain types of non-Hodgkin's lymphoma. Fluro-deoxy-glucose (FDG) is a radioactive compound used for imaging. The metabolism of FDG in the body can be seen on PET scans. Since cancer cells are more metabolically active and use more glucose, these cells light up on scans as abnormal activity. The Deauville scale is based on visual interpretation of FDG uptake. Reference organs are the mediastinum and liver.

Score
PET/CT scan result
1
No uptake
2
Uptake mediastinum
3
Uptake > mediastinum but liver
4
Uptake moderately higher than liver
5
Uptake markedly higher than liver and/or new lesions

Complete metabolic response: scores 1-3 with absence of FDG-avid bone marrow lesions

Partial response: Deauville score 4-5, provided that uptake is decreased compared to baseline and absence of structural progression development

Stable disease (no metabolic response): Deauville score 4-5 without significant change in FDG uptake from baseline

Progressive disease: Deauville score 4-5 with increasing intensity compared to baseline or any interim scan or new FDG-avid focus consistent with malignant lymphoma

US FOOD AND DRUG ADMINISTRATION (FDA) STATUS

Nivolumab (Opdivo®) was approved by the FDA on December 22, 2014, for the treatment of individuals with unresectable or metastatic melanoma and disease progression following ipilimumab (Yervoy®) and, if BRAF V600 mutation--positive, a BRAF inhibitor. Supplemental approvals for nivolumab (Opdivo®) have since been issued by the FDA. Nivolumab (Opdivo®) is administered as an intravenous infusion over 60 minutes.

Pembrolizumab (Keytruda®) was approved by the FDA on September 4, 2014 for the treatment of individuals with unresectable or metastatic melanoma and disease progression following ipilimumab (Yervoy®) and, if BRAF V600 mutation-positive, a BRAF inhibitor. Supplemental approvals for pembrolizumab (Keytruda®) have since been issued by the FDA. Pembrolizumab (Keytruda®) is administered as an intravenous infusion over 30 minutes.

Atezolizumab (Tecentriq®) was approved by the FDA on May 18, 2016 for the treatment of individuals with locally advanced or metastatic urothelial carcinoma who either have disease progression during or following platinum-containing chemotherapy or have disease progression within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy. Supplemental approvals for atezolizumab (Tecentriq®) have since been issued by the FDA. Atezolizumab (Tecentriq®) is administered as an intravenous infusion over 60 minutes.

Avelumab (Bavencio®) was approved by the FDA on March 23, 2017 for the treatment of adult and pediatric individuals ages 12 years and older with metastatic Merkel cell carcinoma. Supplemental approvals for avelumab (Bavencio®) have since been issued by the FDA. Avelumab (Bavencio®) is administered as an intravenous infusion over 60 minutes.

Durvalumab (Imfinzi) was approved by the FDA on May 1, 2017 for the treatment individuals with locally advanced or metastatic urothelial carcinoma who either have disease progression during or following platinum-containing chemotherapy or have disease progression within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy. Supplemental approvals for durvalumab (Imfinzi) have since been issued by the FDA. Durvalumab (Imfinzi) is administered as an intravenous infusion over 60 minutes.

PEDIATRIC USE

The safety and effectiveness of atezolizumab (Tecentriq®) and durvalumab (Imfinzi) have not been established in pediatric individuals.

Description

In a normal immune response, the body can recognize the presence of tumors and mount a response to eradicate them. The process of eradicating a tumor begins with antigen-presenting cells that gather and process the antigens released by tumors. This activates the T-cells, which proliferate and attack the tumor.

Tumors have learned to evade the normal immune response by exploiting the immune checkpoint pathway. The Programmed Death Receptor-1 (PD-1) is a checkpoint protein expressed on the membrane of activated T-cells. The Programmed Death-Ligand 1 (PD-L1) and The Programmed Death-Ligand 2 (PD-L2) are checkpoint proteins expressed on tumor cells and tumor-infiltrating immune cells. When PD-L1 and PD-L2 attach to PD-1 receptors on the T-cells, the T-cells become inhibited and won't attack the tumor; thus, the tumor can continue to proliferate.

Nivolumab (Opdivo®) and pembrolizumab (Keytruda®) are human monoclonal antibodies and immune checkpoint inhibitors that compete with the tumor for the PD-1 receptor on T-cells and block the T-cell's interaction with the tumor's PD-L1 and PD-L2 ligands. Consequently, the tumor is no longer able to inactivate the T-cells and the antitumor response continues.

Atezolizumab (Tecentriq®), avelumab (Bavencio®), and durvalumab (Imfinzi™) are human monoclonal antibodies and immune checkpoint inhibitors that bind to PD-L1 on tumor cells and tumor-infiltrating immune cells and block the interaction with PD-1 and B7.1 receptors on T-cells and antigen-presenting cells. Consequently, the tumor is no longer able to inactivate the T-cells and the antitumor response continues.

MELANOMA

Melanoma can arise in the cutaneous regions (skin) or in the mucosal regions (mucus membranes such as the gastrointestinal or genitourinary tracts). Cutaneous melanoma is the deadliest form of skin cancer, a cancer which is characterized by the uncontrolled growth of melanocytes (pigment cells). Mucosal melanoma is the rarer form of the two types of melanoma and exhibits a poorer prognosis. Melanoma can be contained to one site or it can spread locally to areas within the same region. Metastatic melanoma is the terminology used to describe a setting where the melanoma spreads beyond the skin surface or mucosal epithelium lining and invades other organs of the body.

According to The American Joint Commission on Cancer (AJCC), individuals with melanoma are categorized into three groups:
  • Stage I-II -- no evidence of metastases; localized
  • Stage III -- regional disease
  • Stage IV -- distant metastatic disease

NON-SMALL CELL LUNG CARCINOMA (NSCLC)

Lung cancer is the leading cause of cancer-related mortality in both men and women, not only in the United States but also throughout the world. In the United States, lung cancer is the second most common cancer. Non-small cell lung cancer (NSCLC) accounts for approximately 85% of all lung cancers, and its subtype, squamous cell lung cancer, accounts for 25-30% of all lung cancers. 

RENAL CELL CARCINOMA (RCC)

In adults, renal cell carcinoma (RCC) accounts for 80-95% of all primary kidney cancers. When diagnosed, 65% of individuals have localized disease confined to the kidney. At 75-85%, the clear cell subtype of RCC accounts for the highest percentage among other subtypes of the disease.

UROTHELIAL CARCINOMA

The urinary tract is composed of the the renal pelvis, ureters, bladder, and urethra. The innermost lining of the urinary tract is composed of urothelial cells. Urothelial carcinoma, also known as transitional cell carcinoma (TCC), is the ninth most common cancer overall worldwide and it accounts for 90% of all bladder cancers. Squamous cell carcinoma comprises 1-7% of upper tract urothelial tumors. Adenocarcinoma accounts for less than 1% of upper tract tumors. Urothelial tumors of the renal pelvis and ureters are rare. Tumors of the renal pelvis account for approximately 5% of all urothelial tumors of the urinary tract.

HEAD AND NECK CANCER

It is estimated that head and neck cancers will account for 3.7% of new cancers in the United States in 2017, which is approximately 63,000 new cases of oral cavity, pharyngeal, and larygneal cancers. Squamous cell carcinoma is the histological type in more than 90% of these tumors, and may occur on the lip, oral cavity, pharynx, larynx, sinuses, salivary glands, or mucosal membranes. Treatment is complex and is dependent on specific site, stage, and pathological findings.

CLASSICAL HODGKIN'S LYMPHOMA (cHL)

Hodgkin's lymphoma is an uncommon malignancy involving the lymph nodes and lymphatic system. The World Health Organization (WHO) divides Hodgkinss lymphoma into 2 types: classical (cHL), which accounts for 95% of cases, and nodular lymphocyte-predominant Hodgkin's lymphoma (NLPHL), which accounts for the other 5%. cHL is characterized by the presence of Reed-Sternberg cells in an inflammatory background. NLPHL lacks the Reed-Sternberg cells and instead has lymphocyte-predominant cells, also know as popcorn cells. With all of the advancements and treatments options available, cHL is curable in at least 80% of patients.

MERKEL CELL CARCINOMA (MCC)

Merkel cell carcinoma (MCC) is a rare, aggressive skin cancer with an incidence of approximately 1,500 cases per year in the United States, with 12% of these cases presenting at stage 4. Merkel cell carcinoma has a high mortality rate, with a 5-year survival of only 30-64%. Common sites of metastasis are the lymph nodes and distant skin sites.

MICROSATELLITE INSTABILITY-HIGH (MSI-H) CANCER

Microsatellite instability (MSI) is a change that occurs in the DNA of some cells in which the number of repeats of microsatellites, which are short repeated DNA sequences, is different than the number of repeats that was in the DNA when it was inherited. This may be caused by a defect in the ability to repair mistakes made when DNA is copied in the cell. MSI may result in colon, endometrial, gastric, ovarian, hepatobiliary, urinary tract, brain, or skin cancers, but is most prevalent in colon cancers, accounting for about 15% of all colorectal cancers. MSI-high is defined as instability in the majority of tested markers. MSI-H tumors have a distinct pathologic phenotype: poorly differentiated, right-sided, expansile growth pattern, histologic heterogeneity, and increased tumor infiltrating lymphocytes with a prominent infllammatory reaction.

MALIGNANT PLEURAL MESOTHELIOMA (MPM)

Malignant pleural mesothelioma (MPM) is a rare cancer that is difficult to treat because most individuals have advanced disease at presentation. There are approximately 2500 individuals diagnosed with mesothelioma each year in the United States. MPM mostly occurs in older men who have been exposed to asbestos. The median overall survival is about 1 year. There are three subtypes of mesothelioma which include epithelioid, sarcomatoid, and biphasic (mixed) epithelioid and sarcomatoid. Epithelioid mesothelioma is the most common of the subtypes and also has the better outcome.

ATEZOLIZUMAB (TECENTRIQ®) INDICATIONS

NON-SMALL CELL LUNG CANCER
On October 18, 2016, the FDA granted supplemental approval of atezolizumab (Tecentriq®) for the treatment of individuals with metastatic non-small cell lung cancer (NSCLC) whose disease progressed during or following platinum-containing chemotherapy. Individuals with EGFR or ALK genomic tumor aberrations should have disease progression on FDA-approved therapy for these aberrations prior to receiving atezolizumab (Tecentriq®).

UROTHELIAL CANCER
On May 18, 2016, the US Food and Drug Administration (FDA) gave accelerated approval of atezolizumab (Tecentriq®) for the treatment of individuals with locally advanced or metastatic urothelial carcinoma who have disease progression during or following platinum-containing chemotherapy or have disease progression within 12 months of neoadjuvant or adjuvant treatment, or in those individuals not eligible for cisplatin-containing chemotherapy.

NIVOLUMAB (OPDIVO®) INDICATIONS

CLASSICAL HODGKIN'S LYMPHOMA
On April 25, 2017, the US Food and Drug Administration (FDA) granted accelerated approval of nivolumab (Opdivo®) for the treatment of classical Hodgkin's lymphoma in adult individuals that has relapsed or progressed after autologous hematopoietic stem cell transplantation (HSCT) and brentuximab vedotin (Adcetris®), or after 3 or more lines of systemic therapy that includes HSCT.

HEAD AND NECK CANCER
On November 10, 2016, the FDA granted supplemental approval of nivolumab (Opdivo®) for the treatment of recurrent or metastatic squamous cell carcinoma of the head and neck with disease progression on or after platinum-based therapy.

MELANOMA
On December 22, 2014, the US Food and Drug Administration (FDA) gave accelerated approval of nivolumab (Opdivo®) for the treatment of individuals with unresectable or metastatic melanoma and disease progression following ipilimumab (Yervoy®) and, if BRAF V600 mutation--positive, a BRAF inhibitor (e.g., vemurafenib [Zelboraf®]). Since then, there have been several modifications to the approval. As of January 23, 2016, the following indications are FDA approved for unresectable or metastatic melanoma:
  • As a single agent for the treatment of individuals with BRAF V600 wild-type unresectable or metastatic melanoma.
  • As a single agent for the treatment of individuals with BRAF V600 mutation-positive unresectable or metastatic melanoma. This indication is approved under accelerated approval based on progression-free survival. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.
  • In combination with ipilimumab (Yervoy®), is indicated for the treatment of individuals with unresectable or metastatic melanoma. This indication is approved under accelerated approval based on progression-free survival. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.

MICROSATELLITE INSTABILITY-HIGH CANCER
On July 31, 2017, the US FDA granted accelerated approval of nivolumab (Opdivo®) for the treatment of adult and pediatric individuals (ages 12 years and older) with microsatellite instability-high (MSI-H) or mismatch repair deficient metastatic colorectal cancer that has progressed following treatment with fluoropyrimidine, oxaliplatin, and irinotecan.

NON-SMALL CELL LUNG CANCER
On September 30, 2015, the FDA granted supplemental approval of nivolumab (Opdivo®) for the treatment of individuals with metastatic squamous non-small cell lung cancer (NSCLC) with progression on or after platinum-based chemotherapy. In October 2015, the approval was expanded to include both metastatic squamous and non-squamous NSCLS. Additionally, those "with EGFR or ALK genomic tumor aberrations should have disease progression on FDA-approved therapy for these aberrations prior to receiving nivolumab (Opdivo®)."

RENAL CELL CARCINOMA
On November 23, 2015, the FDA granted supplemental approval of nivolumab (Opdivo®) for the treatment of advanced renal cell carcinoma (RCC) in those who have received prior anti-angiogenic therapy.

UROTHELIAL CARCINOMA
On February 2, 2017, the FDA gave accelerated approval of nivolumab (Opdivo®) for the treatment of locally advanced or metastatic urothelial carcinoma in individuals who have disease progression during or following platinum-containing chemotherapy, or those who have disease progression within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy.

PEMBROLIZUMAB (KEYTRUDA®) INDICATIONS

CLASSICAL HODGKIN'S LYMPHOMA
On March 14, 2017, the US Food and Drug Administration (FDA) granted accelerated approval pembrolizumab (Keytruda®) for the treatment of adult and pediatric individuals with refractory classical Hodgkin's lymphoma, or in those who have relapsed after 3 or more prior lines of therapy.

HEAD AND NECK CANCER
On August 5, 2016, the US FDA granted accelerated approval of pembrolizumab (Keytruda®) for the treatment of individuals with recurrent or metastatic head and neck squamous cell cancer (HNSCC) with disease progression on or after platinum-containing chemotherapy.

MELANOMA
On September 4, 2014, the US Food and Drug Administration (FDA) gave accelerated approval of pembrolizumab (Keytruda®) for the treatment of individuals with unresectable or metastatic melanoma and disease progression following ipilimumab (Yervoy®) and, if BRAF V600 mutation--positive, a BRAF inhibitor (e.g., vemurafenib [Zelboraf®]). This indication was modified on December 18, 2015 to state that pembrolizumab (Keytruda®) is indicated for the treatment of individuals with unresectable or metastatic melanoma; no other criteria are stated as previously.

MICROSATELLITE INSTABILITY-HIGH CANCER
On May 23, 2017, the US FDA granted accelerated approval of pembrolizumab (Keytruda®) for the treatment of adult and pediatric individuals with unresectable or metastatic, microsatellite instability-high (MSI-H) or mismatch repair deficient:
  • solid tumors that have progressed following prior treatment and who have no satisfactory alternative treatment options; or
  • colorectal cancer that has progressed following treatment with fluoropyrimidine, oxaliplatin, and irinotecan.

Limitation of use: the safety and effectiveness of pembrolizumab (Keytruda®) in pediatric individuals with MSI-H central nervous system cancers have not been established.

NON-SMALL CELL LUNG CANCER
On October 2, 2015, the US FDA gave approval for use of pembrolizumab (Keytruda®):
  • As a single agent for:
    • first-line treatment of individuals with metastatic non-small cell lung cancer (NSCLC) whose tumors have high PD-L1 expression as determined by an FDA-approved test with no EGFR or ALK genomic aberrations
    • treatment of individuals with metastatic NSCLC whose tumors express PD-L1 as determined by an FDA-approved test, with disease progression on or after platinum-containing chemotherapy. Individuals with EGFR or ALK genomic tumor aberrations should have disease progression on FDA-approved therapy for these aberrations prior to receiving pembrolizumab (Keytruda®).
  • In combination with pemetrexed and carboplatin as first-line therapy in individuals with metastatic non-squamous NSCLC.

UROTHELIAL CARCINOMA
On May 18, 2017, approval by the US FDA was granted for the use of pembrolizumab (Keytruda®) in the treatment of individuals with locally advanced or metastatic urothelial carcinoma who are not eligible for cisplatin-containing chemotherapy, or who have disease progression during or following platinum-containing chemotherapy, or within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy.

AVELUMAB (BAVENCIO®) INDICATIONS

MERKEL CELL CARCINOMA
On March 23, 2017, the US Food and Drug Administration (FDA) granted approval for avelumab (Bavencio®) for the treatment of adult and pediatric individuals 12 years and older with metastatic Merkel cell carcinoma (MCC).

UROTHELIAL CARCINOMA
On May 9, 2017, avelumab (Bavencio®) was approved by the US FDA for the treatment of individuals with locally advanced or metastatic urothelial carcinoma who have disease progression during or following platinum-containing chemotherapy, or who have disease progression within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy.

DURVALUMAB (IMFINZI) INDICATIONS

UROTHELIAL CARCINOMA
On May 1, 2017, the US FDA granted approval for durvalumab (Imfinzi) for the treatment of individuals with locally advanced or metastatic urothelial carcinoma who have disease progression during or following platinum-containing chemotherapy, or who have disease progression within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy.

OFF-LABEL INDICATIONS

There may be additional indications contained in the Policy section of this document due to evaluation of criteria highlighted in the Company’s off-label policy, and/or review of clinical guidelines issued by leading professional organizations and government entities.
References


American Cancer Society. Bladder cancer stages. Last Revised: 05/23/2016. Available at: http://www.cancer.org/cancer/bladdercancer/detailedguide/bladder-cancer-staging. Accessed July 10, 2017.

American Cancer Society. What is bladder cancer? Last Medical Review: 01/26/2016. Available at:
http://www.cancer.org/cancer/bladdercancer/detailedguide/bladder-cancer-what-is-bladder-cancer. Accessed July 10, 2017.

American Hospital Formulary Service (AHFS). Drug Information 2017. Atezolizumab (Tecentriq®). [Lexicomp Online Web Site]. Updated 03/08/2017. Available at: http://online.lexi.com/lco/action/home [via subscription only]. Accessed July 6, 2017.

American Hospital Formulary Service (AHFS). Drug Information 2017. Avelumab (Bavencio®) . [Lexicomp Online Web Site]. Updated 05/03/2017. Available at: http://online.lexi.com/lco/action/home [via subscription only]. Accessed July 7, 2017.

American Hospital Formulary Service (AHFS). Drug Information 2017. Durvalumab (Imfinzi) . [Lexicomp Online Web Site]. Updated 06/15/2017. Available at: http://online.lexi.com/lco/action/home [via subscription only]. Accessed July 7, 2017.

American Hospital Formulary Service (AHFS). Drug Information 2017. Ipilimumab (Yervoy). [Lexicomp Online Web Site] Updated 03/08/2017. Available at: http://online.lexi.com/lco/action/doc/retrieve/docid/essential_ashp/3667635 [via subscription only]. Accessed July 10, 2017.

American Hospital Formulary Service (AHFS). Drug Information 2017. Nivolumab (Opdivo). [Lexicomp Online Web Site] Updated 03/08/2017. Available at: http://online.lexi.com/lco/action/doc/retrieve/docid/essential_ashp/5887111 [via subscription only]. Accessed July 10, 2017.

American Hospital Formulary Service (AHFS). Drug Information 2017. Pembrolizumab (Keytruda). [Lexicomp Online Web Site] Updated 03/08/17. Available at:http://online.lexi.com/lco/action/doc/retrieve/docid/complete_ashp/5712716 [via subscription only]. Accessed July 7, 2017.

Atezolizumab (Tecentriq®). package insert. Genentech, Inc. South San Francisco, CA. 04/2017. Available at: https://www.tecentriq.com/. Accessed July 6, 2017.

Avelumab (Bavencio®). Package insert. EMD Serona, Inc. Rockland, MA. 05/2017. Available at: https://www.bavencio.com/en_US/for-us-healthcare-professionals.html. Accessed July 7, 2017.

Atkins MB, Choueiri TK. Epidemiology, pathology, and pathogenesis of renal cell carcinoma. 06/14/2017. UpToDate®. Available at: http://www.uptodate.com/contents/epidemiology-pathology-and-pathogenesis-of-renal-cell-carcinoma?source=search_result&search=renal+cell+carcinoma&selectedTitle=3%7E150 [via subscription only]. Accessed July 10, 2017.

Bellmunt J. Treatment of metastatic urothelial cancer of the bladder and urinary tract. June 26, 2017. UpToDate®. Available at: https://www.uptodate.com/contents/treatment-of-metastatic-urothelial-cancer-of-the-bladder-and-urinary-tract?source=search_result&search=tecentriq&selectedTitle=4~22 [via subscription only]. Accessed July 10, 2017.

Borghaei H, Paz-Ares L, Horn L, et al. Nivolumab versus docetaxel in advanced nonsquamous non-small-cell lung cancer. N Engl J Med. 2015;373(17):1627-39. Epub 2015 Sep 27.

Brahmer J, Reckamp KL, Baas P, et al.Nivolumab versus docetaxel in advanced squamous non-small-cell lung cancer. N Engl J Med. 2015;373(2):123-35. Epub 2015 May 31.

Carvajal RD, Hamid O, Ariyan C. Mucosal melanoma. Updated: 07/07/2017. UpToDate Web Site. Available at: http://www.uptodate.com/contents/mucosal-melanoma?source=search_result&search=mucosal+melanoma&selectedTitle=1%7E10 [via subscription only]. Accessed July 10, 2017.

Durvalumab (Imfinzi) Package Insert. AstraZeneca Pharmaceuticals LP; Wilmington, DE. Updated 05/2017. Available at: https://www.imfinzi.com/. Accessed June 16, 2017.

Elsevier’s Gold Standard Clinical Pharmacology Compendium. Ipilimumab (Yervoy). 03/09/17. [Clinical Pharmacology Web site]. Available at: https://www.clinicalkey.com [via subscription only]. Accessed July 10, 2017.

Elsevier's Gold Standard Clinical Pharmacology Compendium. Nivolumab.[Clinical Key Web site]. 05/08/17. Available at: https://www.clinicalkey.com [via subscription only]. Accessed July 10, 2017.

Elsevier's Gold Standard Clinical Pharmacology Compendium. Pembrolizumab.[Clinical Key Web site]. 05/24/17. Available at: https://www.clinicalkey.com [via subscription only]. Accessed July 7, 2017.

Fehrenbacher L, Spira A, Ballinger M, et al; POPLAR Study Group. Atezolizumab versus docetaxel for patients with previously treated non-small-cell lung cancer (POPLAR): a multicentre, open-label, phase 2 randomised controlled trial. Lancet. 2016;387(10030):1837-46. Epub 2016 Mar 10.

Garon EB, Rizvi NA, et al; KEYNOTE-001 Investigators. Pembrolizumab for the treatment of non-small-cell lung cancer. N Engl J Med. 2015 May 21;372(21):2018-28. Epub 2015 Apr 19.

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. 2015;(15)01281-7. [Epub ahead of print].

Ipilimumab (Yervoy) Package Insert. Bristol-Myers Squibb; Princeton, NJ. Updated 03/2017. Available at: http://www.yervoy.com/. Accessed July 7, 2017.

Jarrard DF. Urothelial Tumors of the Renal Pelvis and Ureters. Updated 09/19/16. Available at: http://emedicine.medscape.com/article/452449-overview. Accessed July 10, 2017.

Larkin J, Chiarion-Sileni V, Gonzalez R, et al. Combined Nivolumab and Ipilimumab or Monotherapy in Untreated Melanoma. N Engl J Med. 2015;373(1):23-34. Epub 2015 May 31.

Lexi-Drugs Compendium. Atezolizumab (Tecentriq). 06/01/17. [Lexicomp Online Web site]. Available at: http://online.lexi.com/lco/action/home [via subscription only]. Accessed July 6, 2017.

Lexi-Drugs Compendium. Avelumab (Bavencio). 05/25/17. [Lexicomp Online Web site]. Available at: http://online.lexi.com/lco/action/home [via subscription only]. Accessed July 7, 2017.

Lexi-Drugs Compendium. Durvalumab (Imfinzi). 05/02/17. [Lexicomp Online Web site]. Available at: http://online.lexi.com/lco/action/home [via subscription only]. Accessed July 6, 2017.

Lexi-Drugs Compendium. Ipilimumab (Yervoy). 06/19/17. [Lexicomp Online Web site]. Available at: http://online.lexi.com/lco/action/home [via subscription only]. Accessed July 7, 2017.

Lexi-Drugs Compendium. Nivolumab (Opdivo). 06/09/17. [Lexicomp Online Web site]. Available at: http://online.lexi.com/lco/action/home [via subscription only]. Accessed July 7, 2017.

Lexi-Drugs Compendium. Pembrolizumab (Keytruda). 03/08/17. [Lexicomp Online Web site]. Available at: http://online.lexi.com/lco/action/home [via subscription only]. Accessed July 7, 2017.

Motzer RJ, Escudier B, McDermott DF, et al. Nivolumab versus everolimus in advanced renal-cell carcinoma. N Engl J Med. 2015;373(19):1803-13. Epub 2015 Sep 25.

National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines). Version 2.2017; revised 03/13/17. Colon Cancer. [NCCN Website]. Available at: https://www.nccn.org/professionals/physician_gls/pdf/colon.pdf [via free subscription]. Accessed June 29, 2017.

National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines). Version 2.2017; revised 05/08/2017. Head and Neck Cancers. [NCCN Website]. Available at:https://www.nccn.org/professionals/physician_gls/pdf/head-and-neck.pdf [via free subscription]. Accessed June 29, 2017.

National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines). Version 1.2017; revised 03/01/2017. Hodgkin Lymphoma. [NCCN Website]. Available at: https://www.nccn.org/professionals/physician_gls/pdf/hodgkins.pdf [via free subscription]. Accessed June 29, 2017.

National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines). Version 2.2017; revised 10/31/2016. Kidney Cancer. [NCCN Website]. Available at:
http://www.nccn.org/professionals/physician_gls/f_guidelines.asp#kidney [via free subscription only]. Accessed July 7, 2017.

National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines). Version 2.2017; revised 07/07/2017. Malignant Pleural Mesothelioma. [NCCN Website]. Available at:https://www.nccn.org/professionals/physician_gls/pdf/mpm.pdf [via free subscription]. Accessed July 12, 2017.

National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines). Version 1.2017; revised 11/10/2016. Melanoma. [NCCN Website]. Available at: http://www.nccn.org/professionals/physician_gls/f_guidelines.asp#melanoma [via free subscription]. Accessed July 7, 2017.

National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines). Version 1.2017; revised 10/03/16. Merkel Cell Carcinoma. [NCCN Website]. Available at: https://www.nccn.org/professionals/physician_gls/pdf/mcc.pdf [via free subscription]. Accessed June 29, 2017.

National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines). Version 7.2017. Non-small cell lung cancer. Updated 06/22/17. [NCCN Website]. Available at: https://www.nccn.org/professionals/physician_gls/f_guidelines.asp#nscl [via free subscription only]. Accessed July 7, 2017.

National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines). Version 05.2017. Bladder cancer. Updated 05/25/2017. [NCCN Website]. Available at: https://www.nccn.org/professionals/physician_gls/f_guidelines.asp#bladder [via free subscription only]. Accessed July 6, 2017.

National Comprehensive Cancer Network (NCCN). Drugs and Biologics Compendium. Atezolizumab. [NCCN Website]. Available at:
http://www.nccn.org/professionals/drug_compendium/content/contents.asp [via subscription only]. Accessed June 16, 2017.

National Comprehensive Cancer Network (NCCN). Drugs and Biologics Compendium. Durvalumab. [NCCN Website]. Available at:
http://www.nccn.org/professionals/drug_compendium/content/contents.asp [via subscription only]. Accessed June 16, 2017.

National Comprehensive Cancer Network (NCCN). Drugs and Biologics Compendium. Ipilimumab. [NCCN Website]. 2017. Available at:
http://www.nccn.org/professionals/drug_compendium/content/contents.asp [via subscription only]. Accessed July 12, 2017.

National Comprehensive Cancer Network (NCCN). NCCN Drugs & Biologics Compendium.Nivolumab. [NCCN Web site]. 2017. Available at:
http://www.nccn.org/professionals/drug_compendium/content/contents.asp [via subscription only]. Accessed July 12, 2017.

National Comprehensive Cancer Network (NCCN). NCCN Drugs & Biologics Compendium.Pembrolizumab. [NCCN Web site]. 2017. Available at: http://www.nccn.org/professionals/drug_compendium/content/contents.asp [via subscription only]. Accessed July 12, 2017.

Nivolumab (Opdivo®). package insert. Bristol-Myers Squibb Company: Princeton, NJ. 04/2017. Available at: http://www.opdivo.bmscustomerconnect.com/gateway. Accessed June 16, 2017.

Oken MM, Creech RH, Tormey DC, et al. Toxicity and response criteria of the Eastern Cooperative Oncology Group. Am J Clin Oncol.1982;5(6):649-655.

PD-1 Pathway. Bristol-Myers Squibb Company. 2015. http://www.immunooncologyhcp.bmsinformation.com/immune-system/peripheral-t-cell-inhibition . Accessed July 10, 2017.

Pembrolizumab (Keytruda®). package insert. Merck & CO, Inc: Whitehouse Station, NJ. updated 05/2017. Available at: http://www.keytruda.com/. Accessed June 16, 2017.

Postow MA, Hamid O, Carvajal RD. Mucosal melanoma: pathogenesis, clinical behavior, and management. Curr Oncol Rep. 2012;14(5):441-8.

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. Epub 2015 Jun 23.

Rittmeyer A, Barlesi F, Waterkamp D, et al. Atezolizumab versus docetaxel in patients with previously treated non-small-cell lung cancer (OAK): a Phase 3, open-label, multicentre randomised controlled trial [supplementary appendix appears online]. Lancet. E-pub Date: 2016.

Robert C, Long GV, Brady B, et al. Nivolumab in previously untreated melanoma without BRAF mutation. N Engl J Med. 2015;372(4):320-30. Epub 2014 Nov 16.

Robert C, Schachter J, Long GV, et al. Pembrolizumab versus Ipilimumab in Advanced Melanoma. N Engl J Med. April 19, 2015. [Epub ahead of print].

Robert C, Ribas A, Wolchok JD, et al. Anti-programmed-death-receptor-1 treatment with pembrolizumab in ipilimumab-refractory advanced melanoma: a randomised dose-comparison cohort of a phase 1 trial. Lancet. 2014;Jul 14. pii: S0140-6736(14)60958-2. [Epub ahead of print].

Rosenberg JE, Hoffman-Censits J, Powles T, et al. Atezolizumab in patients with locally advanced and metastatic urothelial carcinoma who have progressed following treatment with platinum-based chemotherapy: a single-arm, multicentre, phase 2 trial. Lancet. 2016;387(10031):1909-20. Epub 2016 Mar 4.

Sachdeva K, Curti B, Jana BRP. Renal Cell Carcinoma. 04/03/17. Available at: http://emedicine.medscape.com/article/281340-overview#showall. Accessed July 10, 2017.

Sosman JA. Immunotherapy of advanced melanoma with immune checkpoint inhibition. UpToDate®. 11/02/2015. Available at:http://www.uptodate.com/contents/immunotherapy-of-advanced-melanoma-with-immune-checkpoint-inhibition?source=machineLearning&search=pembrolizumab&selectedTitle=4~14&sectionRank=1&anchor=H175770315#H175770315 [via subscription only]. Accessed July 10, 2017.

Tan W, Huq S. Non-Small Cell Lung Cancer. 06/28/17. [Emedicine Web Site]. Available at: http://emedicine.medscape.com/article/279960-overview#showall. Accessed July 10, 2017.

Tanabe KK, Tyler D. Cutaneous melanoma: In transit metastases. [UpToDate Web Site]. Updated: 01/16/2017. Available at: http://www.uptodate.com/contents/cutaneous-melanoma-management-of-in-transit-metastase [via subscription only]. Accessed July 10, 2017.

Truven Health Analytics Inc. Micromedex Solutions. Atezolizumab (Tecentriq). [Micromedex® Web site]. Updated 07/05/17. Available at: http://www.micromedexsolutions.com/micromedex2/librarian [via subscription only]. Accessed July 7, 2017.

Truven Health Analytics Inc. Micromedex Solutions. Avelumab (Bavencio). [Micromedex® Web site]. Updated 06/21/2017. Available at: http://www.micromedexsolutions.com/micromedex2/librarian [via subscription only]. Accessed July 7, 2017.

Truven Health Analytics Inc. Micromedex Solutions. Durvalumab (Imfinzi). [Micromedex® Web site]. Updated 05/04/2017. Available at: http://www.micromedexsolutions.com/micromedex2/librarian [via subscription only]. Accessed July 6, 2017.

Truven Health Analytics Inc. Micromedex Solutions. Ipilimumab (Yervoy). [Micromedex® Web site]. Updated 04/19/17. Available at: http://www.micromedexsolutions.com/micromedex2/librarian [via subscription only]. Accessed July 7, 2017.

Truven Health Analytics Inc. Micromedex Solutions. Nivolumab (Opdivo). [Micromedex® Web site]. Updated 06/06/17. Available at: http://www.micromedexsolutions.com/micromedex2/librarian [via subscription only]. Accessed July 7, 2017.

Truven Health Analytics, Inc. Micromedex® Solutions. Pembrolizumab (Keytruda®). [Micromedex® Web site]. Updated 06/19/2017. Available at: http://www.micromedexsolutions.com/micromedex2/librarian [via subscription only]. Accessed July 7, 2017.

US Food and Drug Administration (FDA). Center for Drug Evaluation and Research. Drugs @FDA. Atezolizumab (Tecentriq) Prescribing Information. Updated 04/17/2017. Available at: http://www.accessdata.fda.gov/scripts/cder/daf/index.cfm. Accessed June 16, 2017.

US Food and Drug Administration (FDA). Center for Drug Evaluation and Research. Drugs @FDA. Avelumab (Bavencio) Prescribing Information. Updated 05/09/2017. Available at: http://www.accessdata.fda.gov/scripts/cder/drugsatfda/index.cfm. Accessed June 16, 2017.

US Food and Drug Administration (FDA). Center for Drug Evaluation and Research. Drugs @FDA. Ipilimumab (Yervoy) Prescribing Information. Updated 10/2015. Available at: http://www.accessdata.fda.gov/scripts/cder/drugsatfda/index.cfm. Accessed July 7, 2017.

US Food and Drug Administration (FDA). Center for Drug Evaluation and Research. Drugs @FDA. Durvalumab (Imfinzi) Prescribing Information. Updated 05/01/2017. Available at: http://www.accessdata.fda.gov/scripts/cder/drugsatfda/index.cfm. Accessed June 16, 2017.

US Food and Drug Administration (FDA). Center for Drug Evaluation and Research. Drugs @FDA. Nivolumab (Opdivo) Approval letter and Prescribing Information. [FDA Website]. Updated 04/25/2017. Available at: http://www.accessdata.fda.gov/scripts/cder/drugsatfda/index.cfm. Accessed June 16, 2017.

US Food and Drug Administration (FDA). Center for Drug Evaluation and Research. Drugs @FDA. Pembrolizumab (Keytruda®). Approval letter and Prescribing Information. [FDA Website] 05/23/2017. Available at: http://www.accessdata.fda.gov/scripts/cder/drugsatfda/index.cfm?fuseaction=Search.Label_ApprovalHistory#labelinfo. Accessed June 16, 2017.

US Food and Drug Administration (FDA). Center for Drug Evaluation and Research. Medical Devices. List of Cleared or Approved Companion Diagnostic Devices (In Vitro and Imaging Tools). KEYTRUDA® (pembrolizumab). Site Updated 06/29/2017. Available at: http://www.fda.gov/MedicalDevices/ProductsandMedicalProcedures/InVitroDiagnostics/ucm301431.htm. Accessed July 7, 2017.

Weber JS, D'Angelo SP, Minor D, et al. Nivolumab versus chemotherapy in patients with advanced melanoma who progressed after anti-CTLA-4 treatment (CheckMate 037): a randomised, controlled, open-label, phase 3 trial. Lancet Oncol.2015;16(4):375-84. Epub 2015 Mar 18.





Coding

Inclusion of a code in this table does not imply reimbursement. Eligibility, benefits, limitations, exclusions, precertification/referral requirements, provider contracts, and Company policies apply.

The codes listed below are updated on a regular basis, in accordance with nationally accepted coding guidelines. Therefore, this policy applies to any and all future applicable coding changes, revisions, or updates.

In order to ensure optimal reimbursement, all health care services, devices, and pharmaceuticals should be reported using the billing codes and modifiers that most accurately represent the services rendered, unless otherwise directed by the Company.

The Coding Table lists any CPT, ICD-9, ICD-10, and HCPCS billing codes related only to the specific policy in which they appear.

CPT Procedure Code Number(s)

N/A


Professional and outpatient claims with a date of service on or before September 30, 2015, must be billed using ICD-9 codes. Professional and outpatient claims with a date of service on or after October 1, 2015, must be billed using ICD-10 codes.

Facility/Institutional inpatient claims with a date of discharge on or before September 30, 2015, must be billed with ICD-9 codes. Facility/Institutional inpatient claims with a date of discharge on or after October 1, 2015, must be billed with ICD-10 codes.


ICD - 10 Procedure Code Number(s)

N/A


Professional and outpatient claims with a date of service on or before September 30, 2015, must be billed using ICD-9 codes. Professional and outpatient claims with a date of service on or after October 1, 2015, must be billed using ICD-10 codes.

Facility/Institutional inpatient claims with a date of discharge on or before September 30, 2015, must be billed with ICD-9 codes. Facility/Institutional inpatient claims with a date of discharge on or after October 1, 2015, must be billed with ICD-10 codes.


ICD -10 Diagnosis Code Number(s)

See Attachment A


HCPCS Level II Code Number(s)



J9299 Injection, nivolumab, 1 mg

J9271 Injection, pembrolizumab, 1 mg

J9022 Injection, atezolizumab, 10 mg

J9023 Injection, avelumab, 10 mg

J9173 Injection, durvalumab, 10 mg



Revenue Code Number(s)

N/A

Coding and Billing Requirements


Cross References

Attachment A: Programmed Death Receptor-1 (PD-1) Antagonists (e.g., Keytruda®, Opdivo®) and Programmed Death-Ligand 1 (PD-L1) Antagonists (e.g., Tecentriq®, Bavencio®, Imfinzi™)
Description: ICD-10 Codes and Narratives




Policy History

08.01.20j
01/01/2019This policy has been identified for the HCPCS code update, effective 01/01/2019.

The following HCPCS code has been added to this policy:
J9173 Injection, durvalumab, 10 mg

The following HCPCS codes have been removed from this policy:
C9492 Injection, durvalumab, 10 mg
J9999 Not otherwise classified, antineoplastic drugs

08.01.20i
10/01/2018This policy has been identified for the ICD-10 CM code update, effective 10/01/2018.

The following ICD-10 CM codes have been termed from this policy:
C43.11 Malignant melanoma of right eyelid, including canthus
C43.12 Malignant melanoma of left eyelid, including canthus
C4A.11 Merkel cell carcinoma of right eyelid, including canthus
C4A.12 Merkel cell carcinoma of left eyelid, including canthus

The following ICD-10 CM codes have been added to this policy:
C43.111 Malignant melanoma of right upper eyelid, including canthus
C43.112 Malignant melanoma of right lower eyelid, including canthus
C43.121 Malignant melanoma of left upper eyelid, including canthus
C43.122 Malignant melanoma of left lower eyelid, including canthus
C4A.111 Merkel cell carcinoma of right upper eyelid, including canthus
C4A.112 Merkel cell carcinoma of right lower eyelid, including canthus
C4A.121 Merkel cell carcinoma of left upper eyelid, including canthus
C4A.122 Merkel cell carcinoma of left lower eyelid, including canthus

08.01.20h
01/01/2018This policy has been identified for the HCPCS code update, effective 01/01/2018.

The following HCPCS codes have been added to this policy:
J9022 Injection, atezolizumab, 10 mg
J9023 Injection, avelumab, 10 mg

The following HCPCS codes have been removed from this policy:
C9483 Injection, atezolizumab, 10 mg
C9491 Injection, avelumab, 10 mg
Effective 10/05/2017 this policy has been updated to the new policy template format.
Version Effective Date: 01/01/2019
Version Issued Date: 01/03/2019
Version Reissued Date: N/A

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