Medical Policy

 

Subject: Durvalumab (Imfinzi®)
Document #: DRUG.00109 Publish Date:    06/06/2018
Status: Reviewed Last Review Date:    05/03/2018

Description/Scope

This document addresses the use of durvalumab (Imfinzi, AstraZeneca, Wilmington, DE), a human G1 k monoclonal programmed death ligand 1 (PD-L1) antibody for the treatment of locally advanced or metastatic urothelial carcinoma or non-small cell lung cancer (NSCLC).

Note: Please see the following PD-L1 related documents:

Position Statement

Medically Necessary:

Non-Small Cell Lung Cancer (NSCLC):

The use of durvalumab is considered medically necessary as a consolidation therapy in the treatment of unresectable stage III non-small cell lung cancer when all of the following criteria are met:

  1. Stage III locally advanced, unresectable non-small cell lung cancer histologically or cytologically confirmed; and
  2. Disease has not progressed after definitive chemoradiation; and
  3. Individual has a current Eastern Cooperative Oncology Group (ECOG) performance status of 0-2; and
  4. Individual has not received treatment with another anti-PD-1 or anti-PD-L1 agent; and
  5. Individual does not have any of the following:
    1. History of immunodeficiency; or
    2. History of severe autoimmune disease; or
    3. Require systemic immunosuppression; or
    4. Active immune-mediated disease; or
    5. Severe or life-threatening infection; or
    6. Untreated central nervous system (CNS) metastases; and
  6. Until disease progression or a maximum of 12 months of treatment.

Urothelial Carcinoma:

The use of durvalumab is considered medically necessary for the treatment of locally advanced or metastatic urothelial carcinoma when all of the following criteria are met:

  1. Inoperable or metastatic transitional-cell urothelial carcinoma histologically or cytologically confirmed; and
  2. One of the following:
    1. Disease has progressed during or following platinum-containing therapy; or
    2. Disease has progressed within 12 months of neoadjuvant or adjuvant treatment with platinum-containing therapy; and
  3. Individual has a current Eastern Cooperative Oncology Group (ECOG) performance status of 0-2; and
  4. Individual has not received treatment with another anti-PD-1 or anti-PD-L1 agent; and
  5. Individual does not have any of the following:
    1. History of immunodeficiency; or
    2. History of severe autoimmune disease; or
    3. Require systemic immunosuppression; or
    4. Active immune-mediated disease; or
    5. Severe or life-threatening infection; or
    6. Untreated central nervous system (CNS) metastases.

Investigational and Not Medically Necessary:

The use of durvalumab is considered investigational and not medically necessary when the above criteria are not met and for all other uses.

Rationale

On May 1, 2017, the U.S. Food and Drug Administration (FDA) approved durvalumab 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. This indication was approved under an accelerated process and is based on tumor response rate and duration of response. The FDA also included a contingency that continued approval may be based upon verification and description of clinical benefit in confirmatory trials. The FDA approval was based upon an unpublished single arm, open-label study of 182 individuals with locally advanced or metastatic urothelial carcinoma.

On February 16, 2018 the FDA expanded the indications for durvalumab to include treatment of unresectable stage III NSCLC for individuals whose disease has not progressed following concurrent platinum-based chemotherapy and radiation therapy. This application was granted both Priority Review and Breakthrough Therapy designations by the FDA.

NSCLC

Antonia and associates (2017) reported on an interim analysis of a randomized, double-blind, phase 3 study which compared durvalumab to placebo as a consolidation therapy in individuals with stage III, locally advanced, unresectable NSCLC who had not progressed after platinum-based chemoradiotherapy. After chemoradiation individuals were randomized to receive either durvalumab or a placebo. Individuals receiving durvalumab could continue the drug until disease progression. The coprimary end points were identified as progression-free survival (as defined by the Response Evaluation Criteria in Solid Tumors [RECIST] and overall survival. A total of 709 individuals were included in the study. Median progression-free survival was16.8 months in the durvalumab group (95% confidence interval [CI], 13.0 to 18.1) compared to 5.6 months in the placebo group (95% CI, 4.6 to 7.8) (stratified hazard ratio for disease progression or death, 0.52; 95% CI, 0.42 to 0.65; two-sided p<0.001). The 12 and 18 month progression-free survival rate in the durvalumab group was 55.9% and 44.2% respectively compared to the placebo group rates of 35.3% and 27.0% respectively. Grade three or four adverse events (AEs) were reported in 29.9% of the durvalumab group and 26.1% of the placebo group, with pneumonia noted as the most common AE in both groups. AEs leading to death occurred in both the durvalumab and placebo groups, at 4.4% and 5.6% respectively. The longer progression-free survival was documented across all subgroups of individuals, including level of PD-L1 positive tumor cells. The authors noted that the difference in progression-free survival was also present in those in whom a response was not expected.

The National Comprehensive Cancer Network (NCCN) Non-Small Cell Lung Cancer Guidelines (V3. 2018) includes durvalumab as a category 2A treatment option following definitive chemoradiation. Durvalumab therapy is recommended for up to 12 months.

Urothelial Carcinoma

In an open-label, phase 1/2 study by Massard and colleagues (2016), the safety and efficacy of durvalumab was investigated. A total of 61 participants with inoperable or metastatic solid urothelial tumors were treated with durvalumab every 2 weeks for up to 12 months. The majority of participants (93.4%) had received one or more prior systemic therapies and 31.1% had received three or more prior systemic therapies. The primary endpoint was safety and the secondary endpoint was objective response rate. Median duration of follow-up was 4.3 months. A total of 63.9% (39/61) of participants reported a treatment related AE. The most common AEs were low grade and included fatigue, diarrhea, and decreased appetite. There were 3 participants who experienced grade 3 AEs and there were no reported grade 4 or 5 events. In 42 participants, the objective response rate (ORR) was 31.0% (95% CI, 17.6 to 47.1) and 46.4% (95% CI, 27.5 to 66.1) in the PD-L1-positive subgroup, and 0% (95% CI, 0.0 to 23.2) in the PD-L1-negative subgroup.

Powles and associates (2017) reported the interim results of the 2016 Massard study. A total of 191 subjects received treatment until confirmed progressive disease or for up to 12 months. The results were compared with historical controls. At this update, the primary outcome of ORR was 17.8% or 34 of 191 (95% CI: 12.7%-24.0%), which is lower than the previously reported 31%. Secondary outcomes included progression-free survival and overall survival, which were reported as 1.5 months (95% CI, 1.4-1.9 months) and 18.2 months (95% CI, 8.1 months to not estimable), respectively. Seven complete responses were reported. AEs of any grade were reported in 60.7% (116/191) of participants, with 6.8% (13/191) of the AEs being a grade 3 or 4. There were 2 treatment-related AEs which resulted in death. More results are expected as the study is ongoing.

The NCCN Bladder Cancer Guideline (V3. 2018) includes a 2A recommendation for durvalumab as an alternative preferred treatment regimen for individuals with locally advanced or metastatic bladder cancer.

Other Potential Uses

Clinical trials are in progress to study the use of durvalumab as monotherapy and in combination with other medications as first-line therapy for metastatic urothelial cancer. There are several ongoing phase 3 trials involving the use of durvalumab as a monotherapy or in combination with other treatments for squamous cell carcinoma of the head and neck, hairy cell leukemia and multiple myeloma (Jelinek, 2016; Kumar, 2016).

Background/Overview

Urothelial carcinoma is the most common type of bladder cancer. The American Cancer Society (ACS) estimates that in 2018 there will be approximately 81,190 new cases of bladder cancer (about 62,380 in men and 18,810 in women) and 17,240 deaths from bladder cancer (about 12,520 in men and 4720 in women) in the United States.

Lung cancer is the second most common type of cancer. NSCLC accounts for 80-85% of all lung cancers. The ACS estimates that in 2018 approximately 234,030 new cases of lung cancer will be diagnosed and 154,050 deaths related to lung cancer will occur. The ACS notes that lung cancer is the leading cause of cancer death, killing more people than colon, breast and prostate cancers combined.

Some tumors express the PD-L1 protein which allows tumors to evade detection by the immune system. PD-L1 is also expressed by immune cells. PD-1 is a key receptor; when bound to PD-L1 it suppresses T-cell mediated immune responses. For those tumors which express PD-L1, blocking this pathway allows T-cells to recognize and kill tumor cells. PD-L1 expression can be measured in either the tumor cells or the immune cells. Currently, the assays for PD-L1 expression are not standardized (Brower, 2016).

Imfinzi (durvalumab) 2018 FDA Product Information label includes the following warnings and precautions:

Definitions

Definitive treatment: The clinical treatment that is recognized by expert consensus as the best choice for a cure or sustained disease remission after all other choices have been considered. Also referred to as curative therapy, when it effects a cure or a complete and sustained disease remission.

ECOG Performance Status: A scale and criteria are used by doctors and researchers to assess how an individual’s disease is progressing, assess how the disease affects the daily living abilities of the individual, and determine appropriate treatment and prognosis. This scale may also be referred to as the WHO (World Health Organization) or Zubrod score which is based on the following scale:

Locally advanced cancer: Cancer that has spread from where it started to nearby tissue or lymph nodes.

Metastatic: The spread of cancer from one part of the body to another. A metastatic tumor contains cells that are like those in the original (primary) tumor and have spread.

Monoclonal antibody: A laboratory-produced substance that can locate and bind to specific cells wherever they are in the body. Monoclonal antibodies can be used alone, or they can be used to deliver drugs, toxins, or radioactive material directly to the target cell.

Palliative therapy: Treatment given in a non-curative setting to prolong survival or relieve the symptoms and reduce the suffering caused by cancer.

Coding

The following codes for treatments and procedures applicable to this document are included below for informational purposes. Inclusion or exclusion of a procedure, diagnosis or device code(s) does not constitute or imply member coverage or provider reimbursement policy. Please refer to the member's contract benefits in effect at the time of service to determine coverage or non-coverage of these services as it applies to an individual member.

When services may be Medically Necessary when criteria are met:

HCPCS

 

C9492

Injection, durvalumab, 10 mg [Imfinzi]

J3590

Unclassified biologics [when specified as durvalumab (Imfinzi)]

J9999

Not otherwise classified, antineoplastic drugs [when specified as durvalumab (Imfinzi)]

 

 

ICD-10 Diagnosis

 

 

C34.00-C34.92

Malignant neoplasm of bronchus and lung

 

C61

Malignant neoplasm of prostate

 

C65.1-C65.9

Malignant neoplasm of renal pelvis

 

C66.1-C66.9

Malignant neoplasm of ureter

 

C67.0-C67.9

Malignant neoplasm of bladder

 

C68.0

Malignant neoplasm of urethra

 

Z85.110-Z85.118

Personal history of malignant neoplasm of bronchus and lung

 

Z85.51

Personal history of malignant neoplasm of bladder

 

Z85.53-Z85.54

Personal history of malignant neoplasm of renal pelvis, ureter

 

When services are Investigational and Not Medically Necessary:
For the procedure and diagnosis codes listed above when criteria are not met or for all other diagnoses not listed; or when the code describes a procedure indicated in the Position Statement section as investigational and not medically necessary.

References

Peer Reviewed Publications:

  1. Antonia SJ, Villegas A, Daniel D, et al; PACIFIC Investigators. Durvalumab after chemoradiotherapy in stage III non-small-cell lung cancer. N Engl J Med. 2017; 377(20):1919-1929.
  2. Brower V. Anti-PD-L1 inhibitor durvalumab in bladder cancer. Lancet Oncol. 2016; 17(7):e275.
  3. Jelinek T, Hajek R. PD-1/PD-L1 inhibitors in multiple myeloma: The present and the future. Oncoimmunology. 2016; 5(12):e1254856.
  4. Kumar R, Collins D, Dolly S, et al. Targeting the PD-1/PD-L1 axis in non-small cell lung cancer. Curr Probl Cancer. 2016. pii: S0147-0272(16)30188-X.
  5. Levy A, Massard C, Soria JC, Deutsch E. Concurrent irradiation with the anti-programmed cell death ligand-1 immune checkpoint blocker durvalumab: Single centre subset analysis from a phase 1/2 trial. Eur J Cancer. 2016; 68:156-162.
  6. Massard C, Gordon MS, Sharma S, et al. Safety and efficacy of durvalumab (MEDI4736), an anti-programmed cell death ligand-1 immune checkpoint inhibitor, in patients with advanced urothelial bladder cancer. J Clin Oncol. 2016; 34(26):3119-3125.
  7. Peters S, Antonia S, Goldberg SB, et al. 191TiP: MYSTIC: a global, phase 3 study of durvalumab (MEDI4736) plus tremelimumab combination therapy or durvalumab monotherapy versus platinum-based chemotherapy; (CT) in the first-line treatment of patients (pts) with advanced stage IV NSCLC. J Thorac Oncol. 2016; 11(4 Suppl):S139-s140.
  8. Powles T, O'Donnell PH, Massard C, et al. Efficacy and safety of durvalumab in locally advanced or metastatic urothelial carcinoma: Updated results from a phase 1/2 open-label study. JAMA Oncol. 2017; 3(9):e172411.
  9. Rothschild SI, Zippelius A, Prince SS, et al. 129TiP: SAKK 16/14 - anti-PD-L1 antibody durvalumab (MEDI4736) in addition to neoadjuvant chemotherapy in patients with stage IIIA (N2) non-small cell lung cancer (NSCLC). A multicenter single-arm phase II trial. J Thorac Oncol. 2016; 11(4 Suppl):S112.
  10. Sunshine J, Taube JM. PD-1/PD-L1 inhibitors. Curr Opin Pharmacol. 2015; 23:32-38.

Government Agency, Medical Society, and Other Authoritative Publications:

  1. American Cancer Society (ACS).
  2. American Society of Clinical Oncology (ASCO). Treatment of Non-Metastatic Muscle-Invasive Bladder Cancer: AUA/ASCO/ASTRO/SUO Guideline. 2017. Available at: http://www.auanet.org/guidelines/muscle-invasive-bladder-cancer-new-(2017). Accessed on March 22, 2018.
  3. Durvalumab Monograph. Lexicomp® Online, American Hospital Formulary Service® (AHFS®) Online, Hudson, Ohio, Lexi-Comp., Inc. Last revised May 15, 2017. Accessed on March 19, 2018.
  4. Durvalumab (systemic). In: DrugPoints® System (electronic version). Truven Health Analytics, Greenwood Village, CO. Updated February 20, 2018. Available at: http://www.micromedexsolutions.com. Accessed on March 19, 2018.
  5. National Comprehensive Cancer Network®. NCCN Drugs & Biologic Compendium™ (electronic version). For additional information visit the NCCN website: http://www.nccn.org. Accessed on March 19, 2018.
  6. NCCN Clinical Practice Guidelines in Oncology™. © 2018 National Comprehensive Cancer Network, Inc.  For additional information visit the NCCN website: http://www.nccn.org/index.asp. Accessed on March 22, 2018.
    • Bladder Cancer. V3.2018. Revised March 14, 2018.
    • Non-Small Cell Lung Cancer. V3.2018. Revised February 21, 2018.
  7. IMFINZI® (durvalumab) [Product Information]. Wilmington, DE. AstraZeneca. February 2018. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/761069s002lbl.pdf. Accessed on March 22, 2018.
Websites for Additional Information
  1. American Cancer Society. Immune checkpoint inhibitors to treat cancer. Last revised: May 1, 2017. Available at: https://www.cancer.org/treatment/treatments-and-side-effects/treatment-types/immunotherapy/immune-checkpoint-inhibitors.html. Accessed on March 22, 2018.
  2. National Cancer Institute (NCI). NCI Drug Dictionary. Durvalumab. Available at: https://www.cancer.gov/publications/dictionaries/cancer-drug?cdrid=740856. Accessed on March 22, 2018.
Index

Anti-PD-L1 Monoclonal Antibody
MEDI4736

The use of specific product names is illustrative only. It is not intended to be a recommendation of one product over another, and is not intended to represent a complete listing of all products available.

Document History

Status

Date

Action

Reviewed

05/03/2018

Medical Policy & Technology Assessment Committee (MPTAC) review.

Reviewed

05/02/2018

Hematology/Oncology Subcommittee review. Revised the ™ in the title to ®. Updated Rationale, Background, References and Website sections.

Revised

11/02/2017

MPTAC review.

Revised

11/01/2017

Hematology/Oncology Subcommittee review. Added medically necessary indications for non-small cell lung cancer. Updated Discussion, Definitions, References and Coding sections. The document header wording updated from “Current Effective Date” to “Publish Date.”

 

10/01/2017

Updated Coding section with 10/01/2017 HCPCS changes.

Revised

06/13/2017

MPTAC review.

Revised

06/07/2017

Hematology/Oncology Subcommittee review. ECOG performance status criteria revised from 0-1 to 0-2.

New

05/04/2017

MPTAC review.

New

05/03/2017

Hematology/Oncology Subcommittee review. Initial document development.