Description

Atezolizumab (Tecentriq®) is a monoclonal antibody which binds to programmed death-ligand 1 (PD-L1) expressed on tumor cells or tumor-infiltrating immune cells and blocks its interaction with Programmed Death Receptor 1 (PD-1) and B7.1 receptors present on T cells and antigen-presenting cells, which releases the inhibition of the immune response and activates the antitumor response.

Avelumab (Bavencio®) binds PD-L1, blocking interaction with receptors PD-1 and B7.1. This blockade results in a release of the inhibitory effects of PD-L1 on the immune response and the restoration of antitumor immune responses.

Cemiplimab-rwlc (Libtayo®) binds PD-1 blocking interaction with PD-L1 and PD-L2 releasing PD-1 pathway-mediated inhibition of the immune response, including the anti-tumor immune response.

Durvalumab (Imfinzi™) binds PD-L1, blocking interaction with PD-1 and CD80 (B7.1). This blockade reduces cytotoxic T-cell activity, proliferation, and cytokine production and allows for immune responses without inducing antibody dependent cell-mediated cytotoxicity.

Nivolumab (Opdivo®) is a monoclonal antibody that binds to the PD-1 receptor and blocks its interaction with PD-L1 and PD-L2, releasing PD-1 pathway-mediated inhibition of the immune response, including the anti-tumor immune response.

Pembrolizumab (Keytruda®) is a monoclonal antibody that binds to the PD-1 receptor, blocking its interaction with PD-L1 and PD-L2, releasing PD-1 pathway-mediated inhibition of the immune response, including the anti-tumor immune response.

FDA--U.S. Food and Drug Administration

NCCN--National Comprehensive Cancer Network

NSCLC--Non-Small Cell Lung Cancer

Criteria

Coverage is subject to the specific terms of the member’s benefit plan.

Federal Employee Program members (FEP) should check with their Retail Pharmacy Program to determine if prior approval is required by calling the Retail Pharmacy Program at 1-800-624-5060 (TTY: 1-800-624-5077). FEP members can also obtain the list through the www.fepblue.org website.

Atezolizumab (Tecentriq) may be considered medically necessary foradult individuals 18 years of age and older for ANY of the following conditions:

Bladder (Urothelial) Cancer (NCCN)

• Used as first-line systemic therapy as a single agent (preferred*) in cisplatin ineligible individuals whose tumors express PD-L1 or who are not eligible for any platinum-containing chemotherapy regardless of PD-L1 expression for:
  • Stage II (cT2, N0) disease if tumor is present following reassessment of tumor status two – three (2-3) months after primary treatment with concurrent chemoradiotherapy; or
  • Stage IIIA (cT3, N0; cT4a, N0; cT1-T4a, N1) disease if tumor is present following reassessment of tumor status two – three (2-3) months after primary treatment with concurrent chemoradiotherapy; or
  • Stage IIIB (cT1-T4a, N2,3) disease as downstaging systemic therapy; or
  • Stage IIIB (cT1-T4a, N2,3) disease following partial response or progression after primary treatment with concurrent chemoradiotherapy; or
  • Stage IVA (cT4b, any N, M0; any T, any N, M1a) disease; or
  • Stage IVB (any T, any N, M1b) disease; or
  • Metastatic or local recurrence post cystectomy; or
• Used as subsequent systemic therapy post-platinum as a single agent (alternative preferred*) for:
  • Stage IIIB (cT1-T4a, N2,3) disease following partial response or progression after primary treatment with down staging systemic therapy; or
  • Stage IVA (cT4b, any N, M0) disease if tumor is present following reassessment of tumor status after primary treatment with systemic therapy; or
  • Stage IVB (any T, any N, M1b) disease; or
  • Metastatic or local recurrence post cystectomy; or

Breast Cancer, Triple-Negative, TNBC (FDA)

• Used in combination with paclitaxel protein-bound for the treatment of unresectable locally advanced or metastatic TNBC with tumors which express PD-L1 (PD-L1 stained tumor-infiltrating immune cells [IC] of any intensity covering ≥ 1% of the tumor area), as determined by an FDA approved test; or

Breast Cancer, Invasive, Mucinous, Ductal, Lobular, Mixed, Metaplastic, Tubular, Inflammatory, Papillary, Unknown (NCCN)

• Preferred therapy in combination with albumin-bound paclitaxel for PD-L1 positive triple negative recurrent or stage IV (M1) disease; or

Lung Cancer, Metastatic, Non-Small Cell Lung Cancer, NSCLC (FDA)

• Disease progression 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); or
• First line treatment of individuals with no epidermal growth factor receptor (EGFR) or anaplastic lymphoma kinase (ALK) genomic tumor aberrations in combination with bevacizumab, paclitaxel and carboplatin; or

Lung Cancer, Non-Small Cell Lung Cancer, NSCLC, Adenocarcinoma (with mixed subtypes), Large Cell Carcinoma, Squamous Cell Carcinoma, (NCCN)

• Preferred single agent as subsequent therapy for recurrent, advanced or metastatic disease in individuals with PS 0-2 and no prior progression on a PD-1/PD-L1 inhibitor; or

Lung Cancer, Non-Small Cell Lung Cancer, NSCLC Adenocarcinoma (with mixed subtypes), Large Cell Carcinoma (NCCN)

• Treatment for recurrent, advanced, or metastatic disease as first-line therapy for PD-L1 expression positive (greater than or equal to 1%) tumors that are EGFR, ALK negative or unknown and no contraindicaionts to the addition of pembrolizumab (Keytruda) or atezolizumab (Tecentriq) and performance status 0-2 in combination with carboplatin, paclitaxel, and bevacizumab for nonsquamous cell histology; or
• Continuation maintenance therapy as a single agent or in combination with bevacizumab for recurrent, advanced or metastatic disease for PD-L1 expression positive (greater than or equal to 1%) tumors that are EGFR ALK negative or unknown and no contraindications to the addition of pembrolizumab (Keytruda) or atezolizumab (Tecentriq) in individuals with performance status 0-2 who achieve tumor response or stable disease following first-line therapy with atezolizumab/carboplatin/paclitaxel/bevacizumab for nonsquamous cell histology; or
• Treatment for recurrent, advanced, or metastatic disease in combination with carboplatin, paclitaxel, and bevacizumab for individuals with performance status (PS) 0-1, no contraindications to the addition of pembrolizumab (Keytruda) or atezolizumab (Tecentriq), and tumors of nonsquamous cell histology as:
  • Initial systemic therapy for EGFR, ALK, ROS1, BRAF negative or unknown, and PDL1 <1% or unknown; or
  • First-line or subsequent therapy for BRAF V600E-mutation positive tumors; or
  • Subsequent therapy for sensitizing EGFR mutation-positive tumors and prior erlotinib, afatinib, gefitinib, osimertinib, or dacomitinib therapy; or
  • Subsequent therapy for ALK rearrangement-positive tumors and prior crizotinib, ceritinib, alectinib, or brigatinib therapy; or
  • Subsequent therapy for ROS1 rearrangement-positive tumors and prior crizotinib or ceritinib therapy; or
• Subsequent therapy for PD-L1 expression-positive (≥1%) tumors and EGFR, ALK negative or unknown and no prior platinum-doublet chemotherapy; or
• Continuation maintenance therapy as a single agent or in combination with bevacizumab (if previously received first-line atezolizumab/carboplatin/paclitaxel/bevacizumab regimen) for recurrent, advanced or metastatic disease, performance status 0-2, and tumors of nonsquamous cell histology in individuals who achieve tumor response or stable disease following initial systemic therapy; or

Lung Cancer, Small Cell Carcinoma (FDA)

• Used in combination with carboplatin and etoposide, for the first-line treatment of individuals with extensive-stage small cell lung cancer (ES-SCLC); or

Lung Cancer, Small Cell Carcinoma (NCCN)

• Preferred initial treatment in combination with etoposide and carboplatin for extensive stage disease in individuals:
  • Without localized symptomatic sites or brain metastases and good PS (0-2); or
  • Without localized symptomatic sites or brain metastases and poor PS (3-4) due to small cell lung cancer; or
  • With localized symptomatic sites; or
  • With brain metastases; or

Urothelial Cancer, Locally Advanced or Metastatic (FDA)

• Individuals who are not eligible for cisplatin-containing chemotherapy and whose tumors express PD-L1 (PD-L1 stained tumor-infiltrating immune cells [IC] covering ≥ 5% of the tumor area), as determined by an FDA-approved test; or
• Individuals who are not eligible for any platinum-containing chemotherapy regardless of PD-L1 status; or
• Individuals who have disease progression during or following any platinum-containing chemotherapy, or within 12 months of neoadjuvant or adjuvant chemotherapy; or

Urothelial Cancer, Upper Genitourinary (GU) or Prostate (NCCN)

• Used as a single agent for metastatic disease as:
  • First-line therapy (preferred*) in cisplatin ineligible individuals (preferred*) whose tumors express PD-L1 or who are not eligible for any platinum-containing chemotherapy regardless of PD-L1 expression; or
  • Subsequent systemic therapy post-platinum (alternative preferred regimen*); or

Urothelial Cancer, Urethra, Primary (NCCN)

• As a single agent for primary treatment for clinical stage T3-4, cN1-2 disease or cN1-2 palpable inguinal lymph nodes as first-line systemic therapy (preferred*) in cisplatin ineligible individuals whose tumors express PD-L1 or who are not eligible for any platinum containing chemotherapy regardless of PD-L1 expression (Note: Chemotherapy regimen based on histology); or
• As a single agent for recurrent or metastatic disease as:
  • First-line therapy (preferred*) in cisplatin ineligible individuals whose tumors express PD-L1 or who are not eligible for any platinum-containing chemotherapy regardless of PD-L1 expression; or
  • Subsequent systemic therapy post-platinum.

The use of atezolizumab (Tecentriq) is considered experimental/investigational and, therefore, non-covered for any other indication not listed above. Scientific evidence does not support the use for any other indication.

Procedure Codes

Avelumab (Bavencio) may be considered medically necessary forANYof the following conditions:

Bladder (Urothelial) Carcinoma, Locally Advanced or Metastatic (FDA)

• Individuals with disease progression during or following platinum-containing chemotherapy; or
• Individuals with disease progression within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy; or

Bladder (Urothelial) Carcinoma (NCCN)

• As subsequent systemic therapy post-platinum as a single agent (alternative preferred*) for:
  • Stage IIIB (cT1-T4a, N2,3) disease following partial response or progression after primary treatment with down staging systemic therapy or concurrent chemoradiotherapy; or
  • Stage IVA (cT4b, any N, M0) disease if tumor is present following reassessment of tumor status after primary treatment with systemic therapy or concurrent chemoradiotherapy; or
  • Stage IVB (any T, any N, M1b) disease; or
  • Metastatic or local recurrence post cystectomy; or

Genitourinary Tract Tumors, Upper, or Urothelial Carcinoma of the Prostate (Bladder) (NCCN)

• As single agent subsequent systemic therapy for metastatic disease post-platinum (alternative preferred regimen*); or

Kidney (Renal) Cell Carcinoma (FDA)

• First-line treatment, in combination with axitinib of individuals with advanced renal cell carcinoma (RCC); or

Kidney Cancer, Clear Cell (NCCN)

• First-line or subsequent therapy, in combination with axitinib of individuals with relapse or stage IV disease and clear cell histology; or

Merkel Cell Carcinoma, MCC (FDA)

• Treatment of adult and pediatric individuals 12 years of age and older with metastatic MCC; or

Merkel Cell Carcinoma, MCC (NCCN)

• Treatment for disseminated, clinical M1 disease with or without surgery and/or radiation therapy; or

Urethra, Primary Carcinoma (Bladder) (NCCN)

• Treatment of individuals with primary carcinoma of the urethra as a single agent for recurrent or metastatic disease as subsequent systemic therapy post-platinum

The use of avelumab (Bavencio) is considered experimental/investigational and, therefore, non-covered for any other indication. Scientific evidence does not support the use for any other indication.

Procedure Codes

Cemiplimab (Libtayo) may be considered medically necessary for ANY of the following conditions:

Squamous Cell Carcinoma, Cutaneous, Locally Advanced or Metastatic (FDA and NCCN)

• Treatment of individuals who are not candidates for curative surgery or curative radiation.

The use of cemiplimab (Libtayo) is considered experimental/investigational and, therefore, non-covered for any other indication. Scientific evidence does not support the use for any other indication.

Procedure Codes

Durvalumab (Imfinzi) may be considered medically necessary forANYof the following conditions:

Bladder (Urothelial) Carcinoma (FDA)

• Treatment of individuals with bladder (urothelial) carcinoma:
  • 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 with platinum-containing chemotherapy; or

Bladder (Urothelial) Carcinoma (NCCN)

• Used as subsequent systemic therapy post-platinum as a single agent for:
  • Stage IIIB (cT1-T4a, N2,3) disease following partial response or progression after primary treatment with down staging systemic therapy or concurrent chemoradiotherapy; or
  • Stage IVA (cT4b, any N, M0) disease if tumor is present following reassessment of tumor status after primary treatment with systemic therapy or concurrent chemoradiotherapy; or
  • Stage IVB (any T, any N, M1b) disease; or
  • Metastatic or local recurrence post cystectomy; or

Genitourinary Tract Tumors, Upper, or Urothelial Carcinoma of the Prostate (Bladder) (NCCN)

• Therapy for metastatic disease asasingle agent subsequent systemic therapy post-platinum (alternative preferred*); or

Lung Cancer, Non-Small Cell Lung Cancer, NSCLC (FDA)

• Unresectable, Stage III disease which has not progressed following concurrent platinum-based chemotherapy and radiation therapy; or

Lung Cancer, Non-Small Cell Lung Cancer, NSCLC, Adenocarcinoma (with mixed subtypes), Squamous Cell Carcinoma, Large Cell Carcinoma (NCCN)

• As consolidation therapy for individuals with unresectable stage III disease, PS 0-1; and
• No disease progression after two (2) or more cycles of definitive chemoradiation; or

Urothelial Cancer, Urethra, Primary (Bladder) (NCCN)

• Single agent for recurrent or metastatic disease as subsequent systemic therapy post-platinum (alternative preferred*) (Note: Chemotherapy regimen based on histology).

The use of durvalumab (Imfinzi) is considered experimental/investigational and, therefore, non-covered for any other indication not listed above. Scientific evidence does not support the use for any other indication.

Procedure Codes

Nivolumab (Opdivo) may be considered medically necessary for ANY of the following conditions:

Anal Carcinoma – Squamous Cell (NCCN)

• Preferred single agent second-line or subsequent therapy for metastatic disease; or

Bladder (Urothelial) Carcinoma (NCCN)

• Used as subsequent systemic therapy post-platinum as a single agent (alternative preferred*) for:
  • Stage IIIB (cT1-T4a, N2,3) disease following partial response or progression after primary treatment with downstaging systemic therapy; or
  • Stage IVA (cT4b, any N, M0) disease if tumor is present following reassessment of tumor status after primary treatment with systemic therapy; or
  • Stage IVB (any T, any N, M1b) disease; or
  • Metastatic or local recurrence post cystectomy; or

Central Nervous System Cancers - Brain Metastases – Limited or Extensive (NCCN)

• Treatment of individuals with melanoma with limited brain metastases as single agent or in combination with ipilimumab:
  • For newly diagnosed brain metastases in select individuals (e.g., individuals with small asymptomatic brain metastases) stable systemic disease or reasonable systemic treatment options; or
  • For recurrent brain metastases; or
• Treatment of individuals with non-small cell lung cancer, NSCLC, with limited brain metastases as a single agent for newly diagnosed brain metastases in select individuals (e.g., individuals with small asymptomatic brain metastases) and stable systemic disease or reasonable systemic treatment options; or
• Treatment of individuals with extensive brain metastases:
  • Used as a single agent or in combination with ipilimumab as treatment for recurrent brain metastases in individuals with melanoma and stable systemic disease or reasonable systemic treatment options; or

Colon or Rectal Cancer, Adenocarcinoma (NCCN)

• As primary treatment as a single agentor in combination with ipilimumabfor unresectable metachronous metastases (defective mismatch repair/high microsatellite instability [dMMR/MSI-H] only) and previous adjuvant FOLFOX (fluorouracil, leucovorin, and oxaliplatin) or CapeOX (capecitabine and oxaliplatin) within the past 12 months; or
• As initial therapy as a single agentor in combination with ipilimumabfor individuals with unresectable advanced or metastatic disease (dMMR/MSI-H only) who are not appropriate for intensive therapy; or
• As subsequent therapy as a single agent (if nivolumab (Opdivo) or pembrolizumab (Keytruda) not previously given) or in combination with ipilimumab (if no previous treatment with a checkpoint inhibitor) for unresectable advanced or metastatic disease (dMMR/MSI-Honly) following previous oxaliplatin- irinotecan- and/or fluoropyrimidine-based therapy; or

Colorectal Cancer (FDA)

• Treatment of individuals 12 years of age or older with microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) metastatic disease that has progressed following treatment with a fluoropyrimidine, oxaliplatin, and irinotecan, as a single agent or in combination with ipilimumab; or

Genitourinary Tract Tumors, Upper, or Urothelial Carcinoma of the Prostate (Bladder) (NCCN)

• As single agent subsequent systemic therapy for metastatic disease post-platinum (alternative preferred*); or

Gestational Trophoblastic Neoplasia (NCCN)

• Single agent for recurrent or progressive intermediate trophoblastic tumor (placental site trophoblastic tumor or epithelioid trophoblastic tumor) following treatment with a platinum/etoposide-containing regimen; or
• Single agent for methotrexate-resistant high-risk disease; or

Head and Neck Cancer (FDA)

• Treatment of individuals with recurrent or metastatic squamous cell carcinoma of the head and neck with disease progression on or after a platinum-based therapy; or

Head and Neck Cancers, Very Advanced, Squamous Cell Carcinoma with Mixed Subtypes (NCCN)

• As single agent second-line or subsequent therapy for non-nasopharyngeal cancer if disease progression on or after platinum-containing chemotherapy or for nasopharyngeal disease if previously treated, recurrent or metastatic non-keratinizing disease in:
  • Newly diagnosed T4b, any N, M0 disease, unresectable nodal disease with no metastases, or who are unfit for surgery and PS 3; or
  • Metastatic (M1) disease at initial presentation or recurrent/persistent disease with distant metastases, or unresectable loco regional recurrence or second primary with prior radiation therapy (RT) and PS 0-2; or
  • Unresectable loco regional recurrence without prior RT and PS 3; or

Hepatocellular Carcinoma, HCC (FDA)

• Treatment of individuals withHCCwho have been previously treated with sorafenib; or

Hepatocellular Carcinoma, HCC, Adenocarcinoma (NCCN)

• Subsequent treatment as a single agent for progressive HCC:
  • In individuals who are Child-Pugh Class A or B7 only; and
    • Are non-transplant candidates with unresectable disease; or
    • Are inoperable by performance status or comorbidity, or have local disease or local disease with minimal extrahepatic disease only; or
    • Have extensive liver tumor burden; or
    • Metastatic disease; or

Kidney (Renal) Cell Carcinoma (FDA)

• Advanced renal cell carcinoma in individulas who have received prior anti-angiogenic therapy; or
• Intermediate or poor risk individuals, with previously untreated advanced renal cell carcinoma, in combination with ipilimumab; or

Kidney (Renal) Cell Carcinoma (RCC), Clear Cell or Non-Clear Cell (NCCN)

• As single-agent therapy for relapse or stage IV disease
  • As preferred subsequent therapy for predominant clear cell histology; or
  • As systemic therapy for non-clear cell histology; or
• In combination with ipilimumab forfour (4) cycles followed by single-agent nivolumab (Opdivo)the treatment of individuals with relapse or stage IV disease:
  • As first-line therapy for clear cell histology and favorable risk; or
  • As preferred first-line therapy for clear cell histology and poor/intermediate risk; or
  • As preferred subsequent therapy for clear cell histology; or

Leukemia, Chronic Lymphocytic, CLL/Small Lymphocytic Lymphoma (NCCN)

• Used as a single agent or in combination with ibrutinib for treatment of histologic (Richter's) transformation to diffuse large B-cell lymphoma (clonally related or unknown clonal status) in individuals with del(17p)/TP53 mutation or who are chemotherapy refractory and unable to receive chemoimmunotherapy; or

Lung Cancer, Non-Small Cell Lung Cancer, NSCLC (FDA)

• MetastaticNSCLCand progression on or after platinum-based chemotherapy. Individuals with EGFR or ALK genomic tumor aberrations should have disease progression on FDA-approved therapy for these aberrations prior to receiving nivolumab (Opdivo); or
• Metastatic small cell lung cancer with progression after platinum based chemotherapy and at least one (1) other line of therapy; or

Lung Cancer, Non-Small Cell Lung Cancer, NSCLC, Adenocarcinoma (with mixed subtypes), Squamous Cell Carcinoma, Large Cell Carcinoma (NCCN)

• Treatment of individuals with recurrent, advanced or metastatic NSCLC as preferred single agent as subsequent therapy in individuals with PS 0-2 and no prior progression on a PD-1/PD-L1 inhibitor; or
• Activity against tumor mutational burden (TMB) as a single agent or in combination with ipilimumab; or

Lung Cancer, Small Cell Lung Cancer, SCLC (NCCN)

• Subsequent systemic therapy for PS 0-2 as a single agent or in combination with ipilimumab for:
  • Relapse within six (6) months following complete or partial response or stable disease with initial treatment; or
  • Primary progressive disease; or

Lymphoma, Hodgkin Classic (FDA)

• Treatment of adult individuals with classical Hodgkin lymphoma that has relapsed or progressed after:
  • Autologous hematopoietic stem cell transplantation (HSCT) and brentuximab vendotin; or
  • Three (3) or more lines of systemic therapy that includes autologous HSCT; or

Lymphoma, Hodgkin Classic, cHL (NCCN)

• Second-line or subsequent systemic therapy (if not previously used) in adult individuals greater than or equal to 18 years of age for relapsed or refractory disease in combination with brentuximab vendotin; or
• Third-line or subsequent systemic therapy for adults individuals greater than or equal to 18 years of age as a single agent for:
  • Disease that has relapsed or progressed after autologous hematopoietic stem cell transplant (HSCT) ± brentuximab vedotin; or
  • Relapsed/refractory disease in individuals who are transplant-ineligible based on comorbidity or failure of second-line chemotherapy; or
  • Post-allogeneic transplant; or
• Palliative therapy as a single agent in older adults (greater than 60 years of age) for:
  • Disease that has relapsed or progressed after autologous HSCT with or without bretuximab vedotin; or
  • Relapsed/refractory disease in individuals who are transplant-ineligible based on comorbidity or failure of second-line chemotherapy; or
  • Post-allogeneic transplant; or

Lymphomas, T-Cell, Extranodal NK/T-Cell Lymphoma, Nasal Type (NCCN)

• Treatmentfor relapsed/refractory disease following additional therapy with an alternate combination chemotherapy regimen (asparaginase-based) not previously used; or

Melanoma (FDA)

• Unresectable or metastatic melanoma, as a single agent or in combination with ipilimumab; or
• Lymph node involvement or metastatic disease in individulas who have undergone complete resection, in the adjuvant setting; or

Melanoma, Cutaneous (NCCN)

• As preferred* adjuvant therapy as a single agent:
  • For resected stage III sentinel node positive disease during active nodal basin ultrasound surveillance or after complete lymph node dissection (CLND); or
  • For stage III disease with clinically positive node(s) following wide excision of primary tumor and a complete therapeutic lymph node dissection; or
  • For stage III disease with clinical or microscopic satellite/in-transit metastases if no evidence of disease post-surgery; or
  • For local satellite/in-transit recurrence if no evidence of disease post-surgery; or
  • Following CLND and/or complete resection of nodal recurrence; or
  • Following complete resection of distant metastatic disease; or
• As First-line therapy as a single agent or in combination with ipilimumab for unresectable or metastatic cutaneous melanoma; or
• Preferred second-line or subsequent therapy for metastatic or unresectable disease after disease progression or maximum clinical benefit from BRAF targeted therapy:
  • Asa single agent or in combination with ipilmumab if checkpoint inhibitor immunotherapy was not previously used; or
  • Incombination with ipilimumab for individuals who progress on single-agent checkpoint inhibitor immunotherapy; or
  • May be considered as re-induction therapy (as a single agent or in combination with ipilimumb)if prior checkpoint inhibitor immunotherapy resulted in disease control (complete response, partial response, or stable disease) and no residual toxicity, and disease progression/relapse occurred greater than three (3) months after treatment discontinuation; or

Melanoma, Uveal (NCCN)

• Treatment of individuals with distant metastatic uveal melanoma as single agent therapy or in combination with ipilimumab; or

Merkel Cell Carcinoma, MCC (NCCN)

• Preferred treatment for disseminated, clinical M1 disease with or without surgery and/or radiation therapy; or

Mesothelioma, Malignant Pleural, Epithelial, Sarcomatoid, or Mixed (NCCN)

• Treatment for individuals with malignant pleural mesothelioma as subsequent systemic therapy as a single agent or in combination with ipilimumab; or

Prostate Cancer, Urothelial (Bladder) Carcinoma (NCCN)

• Therapy for metastatic disease as single agent subsequent systemic therapy post-platinum; or

Small Bowel Adenocarcinoma (NCCN)

• Initial therapy as a single agent for advanced or metastatic disease (deficient mismatch repair/microsatellite instability-high [dMMR/MSI-H] only) in individuals with prior oxaliplatin exposure in the adjuvant setting or contraindication; or
• Subsequent therapy as a single agent for advanced or metastatic disease (deficient mismatch repair/microsatellite instability-high [dMMR/MSI-H] only); or

Urothelial Carcinoma, Locally Advanced or Metastatic (FDA)

• Individuals with disease progression during or following platinum-containing chemotherapy; or
• Individuals with disease progression within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy; or

Urothelial Cancer, Urethra, Primary (Bladder) (NCCN)

• Single agent for recurrent or metastatic disease as subsequent systemic therapy post-platinum (alternative preferred*) (Note: Chemotherapy regimen based on histology).

The use of nivolumab (Opdivo) is considered experimental/investigational and, therefore, non-covered for any other indication not listed above. Scientific evidence does not support the use for any other indication.

Procedure Codes

Pembrolizumab (Keytruda) may be considered medically necessary forANYof the following conditions:

Anal Carcinoma, Squamous Cell Carcinoma (NCCN)

• Treatment of individuals with squamous cell anal carcinoma as second- line or subsequent, single agent therapy for metastatic disease; or

Bladder (Urothelial) Carcinoma (FDA)

• Treatment of individuals with locally advance or metastatic Urothelial Carcinoma who:
  • Are not eligible for cisplatin-containing chemotherapy and whose tumors express PD-L1 (combined Positive Score (CPS) greater than or equal to ten (10) as determined by an FDA-approved test; or
  • Are not eligible for any platinum-containing chemotherapy regardless of PD-L1 status; or
  • 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; or

Bladder (Urothelial) Carcinoma (NCCN)

• As first-line systemic therapy as a single agent (preferred*) in cisplatin ineligible individuals whose tumors express PD-L1 or who are not eligible for any platinum-containing chemotherapy regardless of PD-L1 expression for:
  • Stage II (cT2, N0) disease if tumor is present following reassessment of tumor status two – three (2-3) months after primary treatment with concurrent chemoradiotherapy; or
  • Stage IIIA (cT3, N0; cT4a, N0; cT1-T4a, N1) disease if tumor is present following reassessment of tumor status two – three (2-3) months after primary treatment with concurrent chemoradiotherapy; or
  • Stage IIIB (cT1-T4a, N2,3) disease as downstaging systemic therapy; or
  • Stage IIIB (cT1-T4a, N2,3) disease following partial response or progression after primary treatment with concurrent chemoradiotherapy; or
  • Stage IVA (cT4b, any N, M0; any T, any N, M1a) disease; or
  • Stage IVB (any T, any N, M1b) disease; or
  • Metastatic or local recurrence post cystectomy; or
• As subsequent systemic therapy post-platinum as a single agent (preferred) for:
  • Stage IIIB (cT1-T4a, N2,3) disease following partial response or progression after primary treatment with downstaging systemic therapy; or
  • Stage IVA (cT4b, any N, M0) disease if tumor is present following reassessment of tumor status after primary treatment with systemic therapy; or
  • Stage IVB (any T, any N, M1b) disease; or
  • Metastatic or local recurrence post cystectomy; or

Bladder (Urothelial) Cancer, Urethra, Primary (NCCN)

• Used as a single agent for recurrent or metastatic disease as:
  • First-line systemic therapy in cisplatin ineligible individuals whose tumors express PD-L1 or who are not eligible for any platinum-containing chemotherapy regardless of PD-L1 expression (preferred*); or
  • Subsequent systemic therapy post-platinum (alternative preferred*); or

• • Used as a single agent for primary treatment for clinical stage T3-4, cN1-2 disease or cN1-2 palpable inguinal lymph nodes as first-line systemic therapy in cisplatin ineligible individuals whose tumors express PD-L1 or who are not eligible for any platinum containing chemotherapy regardless of PD-L1 expression (preferred*); or

Central Nervous System Cancers - Extensive Brain Metastases (NCCN)

• Single-agent treatment for recurrent brain metastases in individuals with melanoma or PD-L1-positive non-small cell lung cancer and stable systemic disease or reasonable systemic treatment options; or

Central Nervous System Cancers - Limited Brain Metastases (NCCN)

• Single-agent treatment for brain metastases in individuals with melanoma or PD-L1-positive non-small cell lung cancer, NSCLC:
  • For newly diagnosed brain metastases in select individuals (e.g., individuals with small asymptomatic brain metastases) and stable systemic disease or reasonable systemic treatment options; or
  • For recurrent brain metastases; or

Cervical Cancer (FDA)

• Treatment of individuals with recurrent or metastatic cervical cancer with disease progression on or after chemotherapy whose tumors express PD-L1 [Combined Positive Score (CPS) greater than or equal to one (1)]; or

Cervical Cancer – Squamous cell carcinoma, Adenocarcinoma (NCCN)

• Preferred second-line therapy as a single agent for recurrent or metastatic disease if:
  • Instability-high, MSI-H, or mismatch repair deficient, dMMR tumors; or
  • Disease progression on or after chemotherapy in individuals whose tumors express PDL1 (CPS ≥1); or

Endometrial Carcinoma (FDA)

• Treatment of individuals with advanced endometrial carcinoma that in not MSI-H or dMMR; and
• Individual has disease progression following prior systemic therapy; and
• Individual is not a candidate for curative surgery or radiation; and
• Pembrolizumab (Keytruda) is given in combination with lenvatinib; or

Esophageal Cancer (FDA)

• Treatment of individuals with recurrent locally advanced or metastatic squamous cell carcinoma of the esophagus whose tumors express PD-L1 [Combined Positive Score (CPS) greater than or equal to 10]; and
• Disease progression after one (1) or more prior lines of systemic therapy; or

Esophageal and Esophagogastric Junction Cancers – Squamous Cell Carcinoma, Adenocarcinoma and Gastric Cancer - Adenocarcinoma (NCCN)

• Treatment of individuals as palliative therapy in non-surgical candidates or unresectable locally advance, recurrent, or metastatic disease and Karnofsky performance score greater than or equal to 60% or Eastern Cooperative Oncology Group (ECOG) performance score less than or equal to two (2) as:
  • Preferred second-line or subsequent therapy as a single agent for microsatellite instability-high (MSI-H) or deficient mismatch repair (dMMR) tumors; or
  • Second-line therapy for esophageal squamous cell carcinoma (SCC), esophageal adenocarcinoma and EGJ adenocarcinoma with PD-L1 expression by CPS of levels greater than or equal to 10; or
  • Third-line or subsequent therapy as a single agent for esophageal and EGJ adenocarcinoma with PD-L1 expression levels by CPS of greater than or equal to one (1); or

Gastric Cancer (FDA)

• Treatment of individuals with recurrent locally advanced or metastatic gastric or gastroesophageal junction adenocarcinoma:
  • Whose tumors express PD-L1 [Combined Positive Score (CPS) greater than or equal to 1]; and
  • With disease progression on or after two (2) or more prior lines of therapy including fluoropyrimidine- and platinum-containing chemotherapy and if appropriate, HER2/neu-targeted therapy; or

Gastric Cancer, Adenocarcinoma (NCCN)

• Palliative therapy for unresectable locally advanced, recurrent, or metastatic disease and Karnofsky performance score ≥60% or ECOG performance score ≤2 as:
  • Preferred second-line or subsequent therapy as a single agent for microsatellite instability-high (MSI-H) or deficient mismatch repair (dMMR) tumors; or
  • Third-line or subsequent therapy as a single agent for gastric adenocarcinoma with PD-L1 expression levels by CPS of ≥1; or

Genitourinary, Upper Tract Tumors or Urothelial Carcinoma of the Prostate (Bladder) (NCCN)

• Used as a single agent for metastatic disease as:
  • First-line systemic therapy in cisplatin ineligible individuals whose tumors express PD-L1 or who are not eligible for any platinum-containing chemotherapy regardless of PD-L1 expression (preferred*); or
  • Subsequent systemic therapy post-platinum (preferred*); or

Gestational Trophoblastic Neoplasia (NCCN)

• • Single-agent for recurrent or progressive intermediate trophoblastic tumor (placental site trophoblastic tumor or epithelioid trophoblastic tumor) following treatment with a platinum/etoposide-containing regimen; or
  • Single-agent for methotrexate-resistant high-risk disease; or

Head and Neck Squamous Cell Cancer, HNSCC (FDA)

• Combination treatment with platinum and FU for first-line treatment of individuals with metastatic or unresectable, recurrent HNSCC; or
• Single agent treatment for first line treatment of individuals with metastatic or unresectable, recurrent HNSCC whose tumors express PD-L1 (Combined Positive Score (CPS) greater than or equal to 1); or
• Single agent treatment of individuals with recurrent or metastatic HNSCC with disease progression on or after platinum-containing chemotherapy; or

Head and Neck Cancer, Very Advanced, Squamous Cell Carcinoma with Mixed Subtypes (NCCN)

• Therapy as single agent first-line therapy option for non-nasopharyngeal cancer if PD-L1 positive tumors in:
  • Newly diagnosed T4b, any N 0-3, M0 disease, unresectable nodal disease with no metastases or for individulas who are unfit for surgery and PS 3; or
  • 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; or
  • Unresectable locoregional recurrence without prior RT and PS 3; or
• Therapy as a preferred single agent second line or subsequent therapy option for non-nasopharyngeal cancer if disease progression on or after platinum-containing chemotherapy or for previously treated PD-L1 positive recurrent or metastatic nasopharyngeal cancer in:
  • Newly diagnosed T4b, any N 0-3, M0 disease, unresectable nodal disease with no metastases or for individulas who are unfit for surgery and PS 3; or
  • 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; or
  • Unresectable locoregional recurrence without prior RT and PS 3; or
• Systemic therapy as a preferred first-line, second-line, or subsequent therapy option for non-nasopharyngeal cancer in combination with fluorouracil and either carboplatin or cisplatin for:
  • Metastatic (M1) disease at initial presentation; or
  • Recurrent/persistent disease with distant metastases; or
  • Unresectable locoregional recurrence or second primary with prior RT; or

Hepatobiliary Cancer, HCC (FDA)

• Treatment of individuals with HCC who have been previously treated with sorafenib; or

Hepatocellular Carcinoma, Adenocarcinoma (NCCN)

• Subsequent treatment as a single agent for progressive disease in individuals (Child-Pugh Class A only) who:
  • Have unresectable disease and are not a transplant candidate; or
  • Are inoperable by performance status or comorbidity, or have local disease or local disease with minimal extrahepatic disease only; or
  • Have metastatic disease or extensive liver tumor burden; or

Kidney (Renal) Cell Carcinoma, RCC (FDA)

• Combination therapy with axitinib, for first line treatment of individuals with advanced RCC; or

Kidney Cancer, Clear Cell (NCCN)

• Used in combination with axitinib for relapsed or stage IV disease;
  • As preferred first-line therapy for clear cell histology and favorable risk; or
  • As preferred first-line therapy for clear cell histology and poor/intermediate risk; or
  • As subsequent therapy for clear cell histology; or

Leukemia, Chronic Lymphocytic /Small Lymphocytic Lymphoma (NCCN)

• As a single agent; or
• in combination with ibrutinib for:
  • Treatment of histologic (Richter's) transformation to diffuse large B-cell lymphoma (clonally related or unknown clonal status); and
  • For individuals with del(17p)/TP53 mutation; or
  • Individuals who are chemotherapy refractory and unable to receive chemoimmunotherapy; or

Lung Cancer, NSCLC (FDA)

• As first-line treatment in combination with pemetrexed and platinum chemotherapy for metastatic nonsquamous NSCLC, with no EGFR or ALK genomic tumor aberrations;or
• As first-line treatment in combination with carboplatin and either paclitaxel or nab-paclitaxel (paclitaxel protein-bound) for metastatic squamous NSCLC;or
• As first-line, single agent for NSCLC expressing PD-L1 (Tumor Proportion Score (TPS) greater than or equal to 1%), with no EGFR or ALK genomic tumor aberrations, and is:
  • Stage III in individuals who are not candidates for surgical resection or definitive chemoradiation; or
  • Metastatic; or
• As a single agent for metastatic NSCLC for tumors with express PD-L1 (TPS greater than or equal to 1%) 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 aberations prior to receiving pembrolizumab (Keytruda); or

Lung Cancer, NSCLC, Adenocarcinoma (with mixed subtypes), Large Cell Carcinoma, Squamous Cell Carcinoma (NCCN)

• Treatment for recurrent, advanced or metastatic disease as first-line therapy for PD-L1 expression-positive (≥1%) tumors that are EGFR, ALK negative or unknown and no contraindications to the addition of pembrolizumab (Keytruda) or atezolizumab (Tecentriq) and performance status 0-2:
  • As a single agent** (preferred if PD-L1 ≥50%); or
  • In combination with pemetrexed and either carboplatin or cisplatin for nonsquamous cell histology (preferred if PD-L1 1-49%); or
  • In combination with either carboplatin or cisplatin and either paclitaxel or albumin-bound paclitaxel for squamous cell histology (preferred if PD-L1 1-49%); or

**Pembrolizumab (Keytruda) monotherapy can be considered for PD-L1 1-49% in individuals with poor PS or other contraindications to combination chemotherapy.

• Continuation maintenance therapy for recurrent, advanced or metastatic disease for PD-L1 expression positive (≥1%) tumors that are EGFR, ALK negative or unknown and no contraindications to the addition of pembrolizumab (Keytruda) or atezolizumab (Tecentriq) and performance status 0-2, who achieve tumor response or stable disease following systemic or first-line therapy:
  • As a single agent if pembrolizumab (Keytruda) monotherapy given first-line for nonsquamous cell histology; or
  • In combination with pemetrexed if given first-line as part of a pembrolizumab/pemetrexed and either cisplatin or carboplatin regimen for nonsquamous cell histology; or
  • As a single agent if pembrolizumab (Keytruda) was given as monotherapy or as part of a pembrolizumab/(cisplatin or carboplatin)/(paclitaxel or albumin-bound paclitaxel) regimen for squamous cell histology; or
• Treatment for recurrent, advanced or metastatic disease in combination with pemetrexed and either carboplatin or cisplatin (as preferred regimens if no contraindications to the addition of pembrolizumab (Keytruda) or atezolizumab (Tecentriq) for nonsquamous cell histology), in combination with carboplatin and either paclitaxel or albumin-bound paclitaxel (as preferred regimens if no contraindications to the addition of pembrolizumab (Keytruda) or atezolizumab (Tecentriq) for squamous cell histology), or incombination with cisplatin and either paclitaxel or albumin-bound paclitaxel (if no contraindications to the addition of pembrolizumab (Keytruda) for squamous cell histology) for individuals with performance status 0-1 as:
  • Initial systemic therapy for EGFR, ALK, ROS1, BRAF negative or unknown, and PDL1 <1% or unknown; or
  • First-line or subsequent therapy for BRAF V600E-mutation positive tumors; or
  • Subsequent therapy for sensitizing EGFR mutation-positive tumors and prior erlotinib, afatinib, gefitinib, osimertinib, or dacomitinib therapy; or
  • Subsequent therapy for ALK rearrangement-positive tumors and prior crizotinib, ceritinib, alectinib or brigatinib therapy; or
  • Subsequent therapy for ROS1 rearrangement-positive tumors and prior crizotinib or ceritinib therapy; or
  • Subsequent therapy for PD-L1 expression-positive (greater than or equal to 1%) tumors and EGFR, ALK negative or unknown and no prior platinum-doubletchemotherapy; or
• Preferred* single agent as subsequent therapy for recurrent, advanced, or metastatic disease in individuals with PS 0-2 and tumors with PD-L1 expression levels greater than or equal to 1% and no prior progression on a PD-1/PD-L1 inhibitor; or

Lung Cancer, NSCLC, Adenocarcinoma (with mixed subtypes), Large Cell Carcinoma (NCCN)

• Continuation maintenance therapy in combination with pemetrexed if given first line as part of a pembrolizumab/pemetrexed and either cisplatin or carboplatin regimen for recurrent, advanced, or metastatic disease and tumors of nonsquamous cell histology, in individuals with PS 0-2, who achieve tumor response or stable disease following initial systemic therapy; or

Lung Cancer, NSCLC, Squamous Cell Carcinoma (NCCN)

• Single-agent continuation maintenance therapy if given first line as part of a pembrolizumab/(carboplatin or cisplatin)/(paclitaxel or albumin-bound paclitaxel) regimen for recurrent, advanced, or metastatic disease and tumors of squamous cell histology, in individuals with PS 0-2 who achieve tumor response or stable disease following initial systemic therapy; or

Lung Cancer, Small Cell (FDA)

• Treatment of metastatic small cell lung cancer with disease progression on or after platinum-based chemotherapy and at least one other prior line of therapy; or

Lung Cancer, Small Cell, Small Cell Carcinoma (NCCN)

• Subsequent systemic therapy for individuals with PS 0-2 as a single agent for:
  • Relapse within six (6) months following complete or partial response or stable disease with initial treatment; or
  • Primary progressive disease; or

Lymphoma, B-Cell, Diffuse Large B-Cell Lymphoma (NCCN)

• Treatment of individuals with relapsed or refractory primary mediastinal large B-cell lymphoma disease; or

Lymphoma, Extranodal Natural Killer T-Cell (NK/T-cell), Nasal Type (NCCN)

• For treatment of relapsed/refractory disease following additional therapy with an alternate combination chemotherapy regimen (asparaginase-based) not previously used, if a clinical trial is unavailable; or

Lymphoma, Hodgkin, Classic, cHL (FDA)

• Treatment of adult and pediatric individuals with:
  • Refractory cHL; or
  • Relapse after three (3) or more prior lines of therapy; or

Lymphoma, Hodgkin, Classic, cHL (NCCN)

• Treatment of Adult individuals aged 18 years and older as third-line or subsequent systemic therapy as a single agent for:
  • Disease that has relapsed or progressed after autologous hematopoietic stem cell transplant (HSCT) with or without brentuximab vedotin; or
  • Relapsed/refractory disease in individuals who are transplant-ineligible based on comorbidity or failure of second-line chemotherapy; or
  • Post-allogeneic transplant; or
• Treatment of individuals greater than 60 years of age as palliative therapy as a single agent for:
  • Disease that has relapsed or progressed after autologous hematopoietic stem cell transplant (HSCT) ± brentuximab vedotin; or
  • Relapsed/refractory disease in individuals who are transplant-ineligible based on comorbidity or failure of second-line chemotherapy; or
  • Post-allogeneic transplant; or

Lymphoma, Primary Mediastinal Large B-Cell (PMBCL) (FDA)

• Treatment of adult and pediatric individuals with:
  • Refractory PMBCL; or
  • Relapse after two (2) or more prior lines of therapy; or

Limitation of Use: pembrolizumab (Keytruda) is not recommended for treatment of individuals with PMBCL who require urgent cytoreductive therapy.

Lymphproliferative Disorders, Primary Cutaneous CD30+ T-Cell (NCCN)

• Therapy for primary cutaneous anaplastic large cell lymphoma (ALCL) with multifocal lesions, or cutaneous ALCL with regional nodes (excludes systemic ALCL), as a single agent for relapsed/refractory disease; or

Melanoma (FDA)

• Treatment of individuals with unresectable or metastatic disease; or
• Adjuvant treatment of individuals with melanoma with involvement of lymph node(s) following complete resection; or

Melanoma – Cutaneous Melanoma (NCCN)

• Adjuvant treatment as a single agent:
  • For stage III sentinel lymph node, SLN, positive disease during active nodal basin ultrasound surveillance or after CLND; or
  • For stage III disease with clinically positive node(s) following wide excision of primary tumor and a complete therapeutic lymph node dissection; or
  • For stage III disease with clinical or microscopic satellite/in-transit metastases if no evidence of disease post-surgery; or
  • For local satellite/in-transit recurrence if no evidence of disease post surgery; or
  • Following CLND and/or complete resection of nodal recurrence; or
  • Following complete resection of distant metastatic disease; or
• First-line Single-agent therapy for metastatic or unresectable disease; or
• Second-line or subsequent therapy as a single agent for metastatic or unresectable disease after disease progression or maximum clinical benefit from BRAF targeted therapy:
  • If anti-PD-1 checkpoint inhibitor immunotherapy was not previously used; or
  • May be considered as re-induction therapy if prior checkpoint inhibitor immunotherapy resulted in disease control (complete response, partial response, or stable disease) and no residual toxicity, and disease progression/relapse occurred greater than three (3) months after treatment discontinuation; or

Melanoma, Uveal (NCCN)

• Consider as single agent therapy for distant metastatic disease; or

Merkel Cell Carcinoma, MCC (FDA)

• Treatment of adult and pediatric individuals with recurrent locally advanced or metastatic MCC; or

Merkel Cell Carcinoma, MCC (NCCN)

• Preferred treatment of individuals with disseminated, clinical M1 disease with or without surgery and/or radiation therapy; or
• Treatment for individuals with recurrent locally advanced disease; or

Mesothelioma, Malignant Pleural, Epithelial, Sarcomatoid, Mixed (NCCN)

• Subsequent systemic therapy as a single agent; or

Microsatellite Instability-High, MSI-H, Cancer (FDA)

• Treatment of adult and pediatric individuals with unresectable or metastatic, 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 a fluoropyrimidine, oxaliplatin, and irinotecan; or

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

Microsatellite Instability-High, MSI-H/Mismatch Repair Deficient, dMMR Cancer(NCCN)

MSI-H central nervous system cancers in pediatric individuals is considered experimental/investigational and, therefore, non-covered. The safety and effectiveness of pembrolizumab (Keytruda) in pediatric individuals with MSI-H central nervous system cancers have not been established.

• As a single agent for resected gross residual disease (R2):
  • Gallbladder Cancer – Adenocarcinoma; or
  • Intrahepatic Cholangiocarcinoma – Adenocarcinoma; or
  • Extrahepatic Cholangiocarcinoma – Adenocarcinoma; or
• As single agent, primary therapy for unresectable or metastatic:
  • Gallbladder Adenocarcinoma; or
  • Intrahepatic Cholangiocarcinoma – Adenocarcinoma; or
  • Extrahepatic Cholangiocarcinoma – Adenocarcinoma; or
• As single agent therapy for unresectable or metastatic disease with progression following prior treatment and have no satisfactory alternative treatment options for:
  • Chondrosarcoma; or
  • Ewing Sarcoma, mesenchymal chondrosarcoma; or
  • Osteosarcoma, dedifferentiated chondrosarcoma, High-Grade undifferentiated pleomorphic sarcoma (UPS); or
  • Penile Cancer; or
• Treatment of individuals with recurrent, metastatic or high-risk tumors that had progression following prior cytotoxic chemotherapy for:
  • Uterine neoplasms, Endometrial Carcinoma; or
• As single agent second-line or subsequent therapy for progression after at least one (1) line of systemic therapy for castration-resistant distant metastatic (M1) disease, if pembrolizumab (Keytruda) not previously received for:
  • Prostate Cancer – Adenocarcinoma; or
• As single agent subsequent third line therapy for:
  • Testicular Pure Seminoma, Nonseminoma cancer; or
• As single agent therapy for recurrent or persistent:
  • Ovarian Cancer/Fallopian Tube/Primary Peritoneal Cancer –Carcinosarcoma, Endometroid Clear Cell, Mucinous, Serous; or
• As single agent, initial therapy for unresectable, advanced or metastatic disease for individuals who are not appropriate for intensive therapy for:
  • Colon Adenocarcinoma; or
  • Rectal Adenocarcinoma; or
• As single agent, primary therapy for unresectable metachronous metastases with previous adjuvant FOLFOX or CapeOx with in the last 12 months for:
  • Colon Adenocarcinoma; or
  • Rectal Adenocarcinoma; or
• As single agent, subsequent therapy (if nivolumab (Opdivo) or pembrolizumab (Keytruda) not previously given) for unresectable, advanced or metastatic disease following oxaliplatin- irinotecan- and/or fluoropyrimidine based therapy for:
  • Colon Adenocarcinoma; or
  • Rectal Adenocarcinoma; or
• Treatment of unresectable/metastatic adrenocortical tumors that have progressed following prior treatment with no satisfactory alternative treatment options; or
• Treatment of dMMR or MSI-H, poorly differentiated (high grade)/large or small cell neuroendocrine and adrenal tumors that have progressed following prior treatment with no satisfactory alternative treatment options; or

Mycosis Fungoides (MF)/Sezary Syndrome (SS) (NCCN)

• Primary systemic therapy for:
  • Stage III MF; or
  • Stage IV Sezary syndrome; or
• Systemic therapy as treatment for:
  • Relapsed or persistent stage IA MF with B1 blood involvement, with or without skin-directed therapy; or
  • Relapsed or persistent stage IB-IIA MFwith B1 blood involvement, with or without skin-directed therapy; or
  • Stage IIB MF with limited tumor lesions refractory to multiple previous therapies, with or without skin-directed therapies; or
  • Relapsed or refractory stage IIB MF with generalized tumor lesions, with or without skin-directed therapies; or
  • Stage IIB MF with generalized tumor lesions that is refractory to multiple previous therapies or progression; or
  • Relapsed or persistent stage III MF, with or without skin-directed therapies; or
  • Stage III MF that is refractory to multiple previous therapies; or
  • Relapsed or persistent stage IV SS; or
  • Relapsed or persistent stage IV non Sezary or visceral disease (solid organ), with or without radiation therapy for local control; or
  • Large cell transformation (LCT) with limited cutaneous lesions that is refractory to multiple previous therapies; or
  • Relapsed or persistent LCT with generalized cutaneous or extracutaneous lesions, with or without skin-directed therapy; or

Pancreatic Adenocarcinoma (NCCN)

• Treatment of individuals with microsatellite instability-high or mismatch repair deficient tumors MSI-H/dMMR tumors with good performance status (ECOG PS 0-1):
  • As second-line therapy as a single agent for locally advanced or metastatic disease and disease progression; or
  • Single agent for:
    • Local recurrence in the pancreatic operative bed after resection; or
    • Metastatic disease with or without local recurrence if greater than or equal to six (6) months from completion of primary therapy; or
    • Metastatic disease with or without local recurrence if less than six (6) months from completion of primary therapy; or

Prostate, Urothelial (Bladder) Carcinoma (NCCN)

• Therapy for metastatic disease as a single agent as:
  • First-line systemic therapy (preferred*) in cisplatin ineligible individuals whose tumors express PD-L1 or who are not eligible for any platinum-containing chemotherapy regardless of PD-L1 expression; or
  • Subsequent systemic therapy post-platinum (preferred regimen*); or

Sarcoma, Soft Tissue (NCCN)

• Single-agent therapy for Alveolar Soft Part Sarcoma; or
• Single agent for the treatment of metastatic undifferentiated pleomorphic sarcoma; or

Thymic Carcinoma (NCCN)

• Second-line therapy for thymic carcinoma as a single agent for unresectable disease following first-line chemotherapy for potentially resectable locally advanced disease, solitary metastasis, or ipsilateral pleural metastasis; or
• Second-line therapy for thymic carcinoma as a single agent for extrathoracic metastatic disease; or

Vulvar Cancer, Squamous Cell Carcinoma (NCCN)

• Second-line therapy as a single agent for advanced, recurrent or metastatic disease if:
  • Microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) tumors; or
  • Disease progression on or after chemotherapy in individuals whose tumors express PD-L1 (Combined Positive Score ≥1)

The use of pembrolizumab (Keytruda) is considered experimental/investigational and, therefore, non-covered for any other indication. Scientific evidence does not support the use for any other indication.

Procedure Codes

NOTE: In addition to the above criteria, product specific dosage and/or frequency limits may apply in accordance with the U.S. Food and Drug Administration (FDA)-approved product prescribing information, national compendia, Centers for Medicare and Medicaid Services (CMS) and other peer reviewed resources or evidence-based guidelines. Blue Cross Blue Shield of North Dakota may deny, in full or in part, reimbursement for utilization that does not fall within the applicable dosage and/or frequency limits.

*Note: Language derived from National Comprehensive Cancer Network (NCCN) guidelines.

Diagnosis Codes

Covered Diagnosis Codes for Procedure Codes J9119

Covered Diagnosis Codes for Procedure Code J9173

Covered Diagnosis Codes for Procedure Code J9299

Covered Diagnosis Codes for Procedure Code J9271

Covered Diagnosis Codes for Procedure Code J9022

Covered Diagnosis Codes for Procedure Code J9023

Professional Statements and Societal Positions Guidelines

NA