Description
The programmed death 1 protein (PD1) is an immune checkpoint receptor expressed by activated T cells. PD-1 binds to its ligands Pd1-L1 and PD1-L2 which are expressed on tumor cells, causing immunosuppression and preventing the immune system from rejecting the tumor.

PD-1 inhibition has been studied in clinical trials in metastatic melanoma, non-small cell lung cancer, small cell lung cancer, hepatocellular carcinoma, head and neck cancer and urothelial cancer.

Duralumab (Imfinzi™) was FDA-approved in May 2017 for the treatment of 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. (U.S. Food and Drug Administration 2017).

Policy
Imfinzi (durvalumab) is considered MEDICALLY NECESSARY for the indications below including FDA-approved indications and compendial uses are considered a covered benefit provided that all the approval criteria are met and the member has no exclusions to the prescribed therapy.

CRITERIA FOR INITIAL APPROVAL

1. Non-small cell lung cancer
   • Authorization of up to 12 months may be granted for treatment of unresectable, stage III NSCLC following concurrent platinum-based chemotherapy and radiation therapy.
   • Treatment of metastatic NSCLC (in combination with tremelimumab and platinum-based chemotherapy) in adults whose tumors have no sensitizing epidermal growth factor receptor mutations or anaplastic lymphoma kinase genomic tumor aberrations.
2. Small cell lung cancer, extensive stage:
   • First-line treatment of extensive-stage small cell lung cancer in combination with etoposide and either carboplatin or cisplatin in adults.
3. Biliary tract cancer:
   • Treatment of locally advanced or metastatic biliary tract cancer (in combination with gemcitabine and cisplatin) in adults.
4. Hepatocellular carcinoma:
   • Treatment of unresectable hepatocellular carcinoma (as a single agent or in combination with tremelimumab) in adults.

CONTINUATION OF THERAPY
All members (including new members) requesting authorization for continuation of therapy must meet all initial authorization criteria with document response to therapy.

All other indications are investigational and/ or unproven and are therefore considered NOT MEDICALLY NECESSARY.

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.

Rationale 
The safety and efficacy of durvalumab for urothelial cancer has been evaluated in one multicenter open-label study, in which 182 patients with locally advanced or metastatic disease were enrolled. Patients had progressed on or after platinum-based therapy. Patients with immunodeficiency, medical conditions that required immunosuppression (defined as greater than or equal to 10mg of prednisone or equivalent), severe autoimmune disease, untreated CNS metastatses, HIV, active TB, hepatitis B or hepatitis C were excluded.  Enrolled patients had a median age of 67, with 72 percent being male. Of the enrolled patients, 70 percent had received cisplatin, 30 percent had received carboplatin, and 35 percent had received two or more prior lines of therapy. Tumor assessments were subsequently performed. Of the 182 patients, five had a complete response and 26 had a partial response.

References 

1. Imfinzi [package insert]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; February 2018.
2. The NCCN Drugs & Biologics Compendium^® © 2017 National Comprehensive Cancer Network, Inc. http://www.nccn.org. Accessed August 3, 2017.
3. NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines^®): Bladder Cancer. Version 5.2017. Accessed August 3, 2017. https://www.nccn.org/professionals/physician_gls/pdf/bladder.pdf. 

Coding Section 

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 Blue Shield Association technology assessment program (TEC) and other nonaffiliated technology evaluation centers, reference to federal regulations, other plan medical policies, and accredited national guidelines.

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

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