Pembrolizumab (Keytruda) - CAM 093

Description
Pembrolizumab (Keytruda) is a humanized monoclonal antibody indicated for the treatment of patients with unresectable or metastatic melanoma and disease progression following ipilimumab (Yervoy) and, if BRAF V600 mutation positive, a BRAF inhibitor.

Pembrolizumab is a humanized monoclonal antibody that works by increasing the ability of the body’s immune system to fight advanced melanoma. Pembrolizumab blocks the interaction between PD-1 (programmed death receptor-1) and its ligands, PD-L1 (programmed death receptor-ligand 1) and PD-L2 (programmed death receptor-ligand 2), and may affect both tumor cells and healthy cells. Immune-mediated adverse reactions occurred with Pembrolizumab including pneumonitis, colitis, hepatitis, hypophysitis, nephritis, hyperthyroidism and hypothyroidism. Based on the severity of the adverse reaction, Pembrolizumab should be withheld or discontinued and corticosteroids administered. Based on its mechanism of action, Pembrolizumab may cause fetal harm when administered to a pregnant woman. Female patients of reproductive potential should be advised of the potential hazard to a fetus.

Policy 
Pembrolizumab for the treatment of melanoma is considered MEDICALLY NECESSARY if all of the following criteria are met:

KEYTRUDA is a programmed death receptor-1 (PD-1)-blocking antibody indicated in:

Breast cancer, triple negative (high-risk, early stage) 

  • Treatment of high-risk early stage triple-negative breast cancer, in combination with chemotherapy as neoadjuvant therapy, then continued as a single agent as adjuvant therapy following surgery. 

Breast cancer, triple negative (locally recurrent unresectable or metastatic) 

  • Treatment of locally recurrent unresectable or metastatic triple-negative breast cancer (in combination with chemotherapy) in patients whose tumors express PD-L1 (combined positive score [CPS] ≥10) as determined by an approved test.

Melanoma

  • for the treatment of patients with unresectable or metastatic melanoma. (1.1) 
  • Adjuvant treatment of melanoma with lymph node(s) involvement following complete resection.

Non-Small Cell Lung Cancer (NSCLC) 

  • as a single agent for the first-line treatment of patients with metastatic NSCLC whose tumors have high PD-L1 expression [(Tumor Proportion Score (TPS) ≥50%)] as determined by an FDA-approved test, with no EGFR or ALK genomic tumor aberrations. (1.2) 
  • as a single agent for the treatment of patients with metastatic NSCLC whose tumors express PD-L1 (TPS ≥1%) as determined by an FDA-approved test, with disease progression on or after platinum-containing chemotherapy. Patients with EGFR or ALK genomic tumor aberrations should have disease progression on FDA-approved therapy for these aberrations prior to receiving KEYTRUDA. (1.2) 
  • in combination with pemetrexed and carboplatin, as first-line treatment of patients with metastatic nonsquamous NSCLC.

Head and Neck Squamous Cell Cancer (HNSCC) 

  • First-line (in combination with platinum and fluorouracil) of metastatic or unresectable recurrent head and neck squamous cell carcinoma (HNSCC).
  • First-line, single-agent treatment of metastatic or unresectable recurrent HNSCC in patients whose tumors express PD-L1 (CPS ≥1), as determined by an approved test.
  • or the treatment of patients with recurrent or metastatic HNSCC with disease progression on or after platinum-containing chemotherapy.

Classical Hodgkin Lymphoma (cHL)  

  • for the treatment of adult and pediatric patients with refractory cHL, or who have relapsed after 2 or more prior lines of therapy

Urothelial Carcinoma 

  • for treatment of Bacillus Calmette-Guerin-unresponsive, high-risk, non-muscle invasive bladder cancer with carcinoma in situ with or without papillary tumors in patients who are ineligible for or have elected not to undergo cystectomy.
  • for the treatment of patients with locally advanced or metastatic urothelial carcinoma who are not eligible for platinum-containing chemotherapy.
  • for the treatment of patients with locally advanced or metastatic urothelial carcinoma who have disease progression during or following platinum-containing chemotherapy or within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy. (1.5) 

Microsatellite Instability-High Cancer

  • for the treatment of adult and pediatric patients 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 a fluoropyrimidine, oxaliplatin, and irinotecan.
  • Limitation of Use: The safety and effectiveness of KEYTRUDA in pediatric patients with MSI-H central nervous system cancers have not been established. (1.6) 

Gastric Cancer 

  • for the treatment of patients with recurrent locally advanced or metastatic gastric or gastroesophageal junction adenocarcinoma whose tumors express PD-L1 [Combined Positive Score (CPS) ≥1] as determined by an FDA-approved test, with disease progression on or after two or more prior lines of therapy including fluoropyrimidine- and platinum-containing chemotherapy and if appropriate, HER2/neu-targeted therapy. 

Esophageal cancer 

  • Treatment of recurrent locally advanced or metastatic squamous cell carcinoma of the esophagus in patients whose tumors express PD-L1 (CPS ≥10) as determined by an approved test, with disease progression after one or more prior lines of systemic therapy.
  • Treatment of locally advanced or metastatic esophageal or gastroesophageal junction (GEJ) (tumors with epicenter 1 to 5 centimeters above the GEJ) carcinoma that is not amenable to surgical resection or definitive chemoradiation (in combination with platinum- and fluoropyrimidine-based chemotherapy).

Cervical Cancer 

  • Treatment of persistent, recurrent, or metastatic cervical cancer (in combination with chemotherapy, with or without bevacizumab) in patients whose tumors express PD-L1 (CPS ≥1), as determined by an approved test.
  • Keytruda is indicated for the treatment of patients with recurrent or metastatic cervical cancer with disease progression on or after chemotherapy whose tumor express PD-L1 [Combined Positive Score (CPS> 1)] as determined by an FDA-approved test.

Primary Mediastinal large B-cell Lymphoma (PMBCL)

  • Keytruda is indicated for the treatment of adult and pediatric patients with refractory PMBCL who have relapsed after 2 or more prior lines of therapy.
  • Limitation of use: Not recommended for treatment of PMBCL in patients who require urgent cytoreductive therapy.
  • malignant pleural mesothelioma
  • Mycosis fungoides/Sézary syndrome, relapsed/refractory

Hepatocellular Carcinoma (HCC) 

  • for the treatment of patients with HCC who have been previously treated with sorafenib. 

Merkel Cell Carcinoma (MCC) 

  • for the treatment of adult and pediatric patients with recurrent locally advanced or metastatic Merkel cell carcinoma. 

Renal Cell Carcinoma (RCC) 

  • in combination with axitinib, for the first-line treatment of patients with advanced RCC.  

Endometrial Carcinoma 

  • in combination with lenvatinib, for the treatment of patients with advanced endometrial carcinoma that is not MSI-H or dMMR, who have disease progression following prior systemic therapy and are not candidates for curative surgery or radiation.

Cutaneous squamous cell carcinoma

  • Treatment of recurrent or metastatic cutaneous squamous cell carcinoma not curable by surgery or radiation. 

Tumor mutational burden-high cancer

  • Treatment of unresectable or metastatic, tumor mutational burden-high solid tumors (TMB-H; ≥10 mutations/megabase [mut/Mb]; as determined by an approved test) in adult and pediatric patients who have progressed following prior treatment and have no satisfactory alternative treatment options.

BlueCross BlueShield of South Carolina recognizes uses and indications of injectable oncology medications (including chemotherapy/systemic therapy, therapeutic radiopharmaceuticals, and selected supportive therapies) to be medically necessary if they are listed in the NCCN Drugs and Biologics Compendium with Categories of Evidence + Consensus of 1, 2A and 2B. Treatments listed with a Category of Evidence and Consensus of 3 are considered unproven and not medically necessary.

Benefits Application
This medical policy relates only to the services or supplies described herein. Please refer to the Member's Benefit Booklet for availability of benefits. Member's benefits may vary according to benefit design; therefore, member benefit language should be reviewed before applying the terms of this medical policy.

References

  1. U. S. Food and Drug Administration. (2014, September). Center for Drug Evaluation and Research. Keytruda® (pembrolizumab) for injection, for intravenous use. Retrieved September 8, 2014 from http://www.accessdata.fda.gov/drugsatfda_docs/label/2014/125514lbl.pdf.
  2. Pembrolizumab (Keytruda). Highlights of prescribing information. September 2014. Available at: http://www.merck.com/product/usa/pi_circulars/k/keytruda/keytruda_pi.pdf

Coding Section

Code Number Description
CPT 81210 BRAF (v-raf murine sarcoma viral oncogene homolog B1) (e.g., colon cancer), gene analysis, V600E variant
  96413 Chemotherapy administration, IV infusion technique; up to 1 hour, single or initial substance/drug
  96414 each additional hour (list in addition to code for primary procedure)
ICD-9 Diagnosis 172.0 - 172.9 Malignant melanoma of skin (incompletely resected or unresectable, metastatic or recurrent melanoma)
  162.0 - 162.9 Malignant neoplasm of Bronchus (incompletely resected or unresectable, metastatic or recurrent melanoma)
ICD-9 Procedure    
HCPCS C9027 Injection, pembrolizumab, 1 mg
  J9228 Injection, ipilimumab, 1 mg
ICD-10-CM (effective 10/01/15) C43.0 - C43.9 Malignant melanoma of skin (incompletely resected or unresectable, metastatic or recurrent melanoma)
  C34.0 - C34.92 Malignant neoplasm of Bronchus (incompletely resected or unresectable, metastatic or recurrent melanoma)
  D03.0 - D03.9 Melanoma in situ (incompletely resected or unresectable, metastatic or recurrent melanoma)
ICD-10-PCS (effective 10/01/15)   ICD-10 codes are only used for inpatient services. There is no specific ICD-10-PCS code for this procedure.
Type of Service    
Place of Service    

Procedure and diagnosis codes on Medical Policy documents are included only as a general reference tool for each policy. They may not be all-inclusive.

This medical policy was developed through consideration of peer-reviewed medical literature generally recognized by the relevant medical community, U.S. FDA approval status, nationally accepted standards of medical practice and accepted standards of medical practice in this community, Blue Cross and Blue Shield Association technology assessment program (TEC) and other non-affiliated technology evaluation centers, reference to federal regulations, other plan medical policies and accredited national guidelines.

"Current Procedural Terminology© American Medical Association.  All Rights Reserved" 

History From 2014 Forward     

11/17/2021 

Annual review, adding criteria for triple negative breast cancer, m;ycosis fungoides, additional criteria for esophogeal and cervical cancer. 

11/16/2020 

Annual review, expanding coverage to include esophageal, small cell lung,and cutaneous squamous cell carcinomas. Also adding tumor mutational burden-high cancer verbiage. Expanded for clarity head and neck squamous cell and urothelial cell carcinoma verbiage. No other changes made. 

10/29/2020 

Interim review to add the statement: BlueCross BlueShield of South Carolina recognizes uses and indications of injectable oncology medications (including chemotherapy/systemic therapy, therapeutic radiopharmaceuticals, and selected supportive therapies) to be medically necessary if they are listed in the NCCN Drugs and Biologics Compendium with Categories of Evidence + Consensus of 1, 2A and 2B. Treatments listed with a Category of Evidence and Consensus of 3 are considered unproven and not medically necessary.

11/01/2019 

Annual review, updating policy verbiage to include medical necessity for recent FDA approval for treatment of hepatocellular carcinoma, Merkel cell carcinoma, renal cell carcinoma and endometrial carcinoma. No other changes. 

11/14/2018 

Annual review, updating policy to include medical necessity coverage for cervical cancer and primary mediastinal large B-cell Lymphoma (PMBCL), also adding list of compendial uses. No other changes 

11/02/2017 

Annual review, updating medical necessity criteria to allow for additional conditions based on FDA updated approvals made in September 2017. No other changes made. 

11/01/2016

Annual review, updating to allow for medical necessity for head and neck squamous cell carcinomas. 

11/09/2015

Annual review, adding medical necessity criteria related to NSCLC and coding. No other changes.

11/04/2015 

Change Category from Medicine to Prescription Drug 

11/04/2014

NEW POLICY

 

Complementary Content
${loading}