2) have disease progression within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy

Policy:

(NOTE: For Medicare Advantage, please refer to the Medicare Coverage Section below for coverage guidance)

The requirements of the Horizon BCBSNJ Durvalumab (Imfinzi) Program may require a precertification/prior authorization via MagellanRx Management. These requirements are member-specific: please verify member eligibility and requirements through the Horizon Provider Portal (www.horizonblue.com/provider). Ordering clinicians should request pre-certification from MagellanRx Management at ih.magellanrx.com or call 1-800-424-4508 (when applicable).

1. Imfinzi (durvalumab) is considered medically necessary for the FDA approved indications when the following criteria are met:
• The prescriber is a specialist in the area of the patient's diagnosis (e.g. oncologist) or has consulted with as specialist in the area of the patient's diagnosis
A. Members with locally advanced or metastatic urothelial carcinoma when ALL of the following criteria are met:
a. Member has had disease progression during or following platinum-containing chemotherapy, OR
b. Member has had disease progression within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy, AND
c. Member is 18 years of age or older, AND
d. Member has an ECOG performance status of 0-1, AND
e. Member has not been previously treated with an anti-PD-1 or anti-PD-L1 antibody (i.e., nivolumab, pembrolizumab, atezolizumab, avelumab) , AND
f. Member does not have any of the following:
i. History of immunodeficiency, OR
ii. A medical condition that requires systemic immunosuppression, OR
iii. History of severe autoimmune disease, OR
iv. Untreated central nervous system (CNS) metastases, OR
v. Human immunodeficiency virus (HIV), OR
vi. Active tuberculosis, OR
vii. Hepatitis B or C infection

B. Members with unresectable, stage III non-small cell lung cancer (NSCLC) whose disease has not progressed following concurrent platinum-based chemotherapy and radiation therapy when ALL of the following criteria are met
a. Member is 18 years of age or older, AND
b. Member has an ECOG performance status of 0-1, AND
c. Member has received at least 2 cycles of platinum-based chemotherapy concurrent with radiation therapy, AND
d. Member has not been previously treated with an anti-PD-1 or anti-PD-L1 antibody (i.e., nivolumab, pembrolizumab, atezolizumab, avelumab) , AND
e. Member does not have any of the following:
i. Active or prior autoimmune disease or history of immunodeficiency.
ii. Evidence of severe or uncontrolled systemic diseases, including active bleeding diatheses or active infections including hepatitis B, C and HIV.
iii. Evidence of uncontrolled illness such as symptomatic congestive heart failure, uncontrolled hypertension or unstable angina pectoris.
iv. Any unresolved toxicity more than Grade 2 from the prior chemoradiation therapy.
v. Active or prior documented inflammatory bowel disease (eg, Crohn's disease, ulcerative colitis).

C. Members with extensive-stage small cell lung cancer (ES-SCLC) as first line treatment when ALL of the following criteria are met:
· Member is 18 years of age or older; AND
· Member has an ECOG performance status of 0-1; AND
· Member will be using the requested agent in combination with etoposide and either carboplatin or cisplatin as one of the following:
· Used as initial therapy in combination with etoposide and either carboplatin or cisplatin; or
· Used as single agent maintenance therapy after initial therapy with etoposide and either carboplatin or cisplatin; AND
· Member has no prior exposure to immune-mediated therapy (except therapeutic anticancer vaccines); AND
· Member does not have any of the following:
o History of chest radiation therapy or planned consolidation chest radiation therapy
o Paraneoplastic syndrome of autoimmune nature
o Active infection including tuberculosis, HIV, hepatitis B and C
o Active or prior documented autoimmune or inflammatory disorders

2. When Imfinzi (durvalumab) is considered medically necessary, initial therapy will be approved for 6 months at the following FDA-approved dose:
a. Locally advanced or metastatic urothelial carcinoma: 10 mg/kg intravenous infusion over 60 minutes every 2 weeks until unacceptable toxicity or disease progression
b. Unresectable, stage III non-small cell lung cancer (NSCLC): 10 mg/kg intravenous infusion over 60 minutes every 2 weeks until unacceptable toxicity, disease progression, or a maximum of 12 months
c. Extensive stage small cell lung cancer: 1500mg in combination with chemotherapy every 3 weeks (21 days) for 4 cycles, followed by 1500mg every 4 weeks as a single agent until unacceptable toxicity or disease progression. Patients with a body weight of ≤ 30 kg must receive weight-based dosing (Imfinzi 20mg/kg in combination with chemotherapy every 3 weeks (21 days) for 4 cycles, followed by 20 mg/kg every 4 weeks as a single agent until weight increases to greater than 30kg)
d. Dose reductions are not recommended as per the FDA approved labeling. If a member experiences adverse reactions, Imfinzi should be withheld and/or discontinued, to manage adverse reactions as described in Table 1:
Table 1:

Adverse Reactions	Severitya	Imfinzi Treatment Modification
Pneumonitis	Grade 2	Withhold doseb until Grade 1 or resolved and corticosteroid dose is less than or equal to prednisone 10 mg per day (or equivalent)
	Grade 3 or 4	Permanently discontinue
Hepatitis	For ALT or AST >3x but ≤ 8xULN or Total bilirubin >1.5 but ≤ 5xULN	Withhold dosebuntil Grade 1 or resolved and corticosteroid dose is less than or equal to prednisone 10 mg per day (or equivalent)
	ALT or AST > 8xULN or total bilirubin >5xULN or Concurrent ALT or AST >3xULN and total bilirubin >2xULN with no other cause	Permanently discontinue
Colitis or diarrhea	Grade 2	Withhold doseb until Grade 1 or resolved and corticosteroid dose is less than or equal to prednisone 10 mg per day (or equivalent)
	Grade 3 or 4	Permanently discontinue
Hyperthyroidism	Grade 2-4	Withhold dose until clinically stable
Adrenal insufficiency, Hypophysitis/Hypopituitarism	Grade 2-4	Withhold dose until clinically stable
Type 1 Diabetes Mellitus	Grade 2-4	Withhold dose until clinically stable
Nephritis	Creatinine >1.5-3xULN	Withhold doseb until Grade 1 or resolved and corticosteroid dose is less than or equal to prednisone 10 mg per day (or equivalent)
	Creatinine >3-6xULN	Permanently discontinue
Rash or dermatitis	Grade 2 for >1 week	Withhold doseb until Grade 1 or resolved and corticosteroid dose is less than or equal to prednisone 10 mg per day (or equivalent)
	Grade 3
	Grade 4	Permanently discontinue
Infection	Grade 3 or 4	Withhold dose until clinically stable
Infusion-related reactions	Grade 1 or 2	Interrupt or slow the rate of infusion
	Grade 3 or 4	Permanently discontinue
Other immune-mediated adverse reactions	Grade 3	Withhold doseb until Grade 1 or resolved and corticosteroid dose is less than or equal to prednisone 10 mg per day (or equivalent)
	Grade 4	Permanently discontinue
Persistent Grade 2 or 3 adverse reaction (excluding endocrinopathies)	Grade 2 or 3 adverse reaction that does not recover to Grade 0 or 1 within 12 weeks of last IMFINZI dose	Permanently discontinue
Inability to taper corticosteroid	Inability to reduce to ≤ to prednisone 10 mg per day (or equivalent) within 12 weeks after the last IMFINZI dose	Permanently discontinue
Recurrent Grade 3 or 4 adverse reaction	Recurrent Grade 3 or 4 (severe or life-threatening) adverse reaction	Permanently discontinue

3. Continuation of Imfinzi (durvalumab) will be approved every 6 months at the FDA-approved dose when the member meets all of the following criteria:
a. Continues to meet initial review criteria
b. There is documented evidence that no unacceptable toxicities have occurred (i.e., member has not had any adverse drug reactions warranting permanent discontinuation of therapy – refer to recommended treatment modifications in Table 1 above)
c. There is documented evidence of efficacy and disease stability and/or improvement (i.e., as demonstrated by tumor assessments)
d. For the indication of unresectable, stage III non-small cell lung cancer (NSCLC), therapy will be approved for one renewal only (total therapy for a maximum of 12 months)

4. Imfinzi (durvalumab) is considered medically necessary for off-label indications that have in effect a rating of 'Category 1' or 'Category 2A' in the current recommendations in the National Comprehensive Cancer Network (NCCN) compendium. Refer to National Comprehensive Cancer Network: Drugs and Biologics Compendium - durvalumab. Available at: [https://www.nccn.org/professionals/drug_compendium/content/].

5. Other uses of Imfinzi (durvalumab) are considered investigational.

There is no National Coverage Determination (NCD) or Local Coverage Determination (LCD) for jurisdiction JL specifically for this service. Therefore, Medicare Advantage will follow the Horizon Policy. See generally: Local Coverage Article: Approved Drugs and Biologicals; Includes Cancer Chemotherapeutic Agents (A53049). Available at: https://www.cms.gov/medicare-coverage-database/details/article-details.aspx?articleId=53049&ver=44&name=314*1&UpdatePeriod=711&bc=AQAAEAAAAAAAAA%3d%3d&.

Medicaid Coverage

For Horizon NJ Health members, please follow this link for the corresponding HNJH drug policy https://services3.horizon-bcbsnj.com/ddn/NJhealthWeb.nsf

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Horizon BCBSNJ Medical Policy Development Process:

This Horizon BCBSNJ Medical Policy (the “Medical Policy”) has been developed by Horizon BCBSNJ’s Medical Policy Committee (the “Committee”) consistent with generally accepted standards of medical practice, and reflects Horizon BCBSNJ’s view of the subject health care services, supplies or procedures, and in what circumstances they are deemed to be medically necessary or experimental/ investigational in nature. This Medical Policy also considers whether and to what degree the subject health care services, supplies or procedures are clinically appropriate, in terms of type, frequency, extent, site and duration and if they are considered effective for the illnesses, injuries or diseases discussed. Where relevant, this Medical Policy considers whether the subject health care services, supplies or procedures are being requested primarily for the convenience of the covered person or the health care provider. It may also consider whether the services, supplies or procedures are more costly than an alternative service or sequence of services, supplies or procedures that are at least as likely to produce equivalent therapeutic or diagnostic results as to the diagnosis or treatment of the relevant illness, injury or disease. In reaching its conclusion regarding what it considers to be the generally accepted standards of medical practice, the Committee reviews and considers the following: all credible scientific evidence published in peer-reviewed medical literature generally recognized by the relevant medical community, physician and health care provider specialty society recommendations, the views of physicians and health care providers practicing in relevant clinical areas (including, but not limited to, the prevailing opinion within the appropriate specialty) and any other relevant factor as determined by applicable State and Federal laws and regulations.

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Index:
Imfinzi
Durvalumab

References:
1. Imfinzi™ (Durvalumab). [Prescribing Information]. AstraZeneca Pharmaceuticals. Wilmington, DE. March 2020.
2. ClinicalTrials.gov. A Phase 1/2 Study to Evaluate MEDI4736. Available from: https://clinicaltrials.gov/ct2/show/record/NCT01693562. Accessed June 2, 2017.
3. National Comprehensive Cancer Network. Bladder Cancer. (Version 3.2019). https://www.nccn.org/professionals/physician_gls/pdf/bladder.pdf. Accessed January 10, 2020.
4. 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
5. National Comprehensive Cancer Network. Non-Small Cell Lung Cancer. (Version 4.2019). https://www.nccn.org/professionals/physician_gls/pdf/nscl.pdf. Accessed May 22, 2019.
6. ClinicalTrials.gov. A Global Study to Assess the Effects of MEDI4736 Following Concurrent Chemoradiation in Patients With Stage III Unresectable Non-Small Cell Lung Cancer (PACIFIC). Available at: https://clinicaltrials.gov/ct2/show/NCT02125461?term=nct02125461. Accessed February 2018.
7. FDA approved durvalumab for extensive-stage small cell lung cancer. Food and Drug Administration. March 27, 2020. Available at: https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-durvalumab-extensive-stage-small-cell-lung-cancer
8. ClinicalTrials.gov. Durvalumab ± Tremelimumab in Combination With Platinum Based Chemotherapy in Untreated Extensive-Stage Small Cell Lung Cancer (CASPIAN). NCT03043872. Available at: https://clinicaltrials.gov/ct2/show/NCT03043872. Accessed March 30, 2020.

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Medical policies can be highly technical and are designed for use by the Horizon BCBSNJ professional staff in making coverage determinations. Members referring to this policy should discuss it with their treating physician, and should refer to their specific benefit plan for the terms, conditions, limitations and exclusions of their coverage.

The Horizon BCBSNJ Medical Policy Manual is proprietary. It is to be used only as authorized by Horizon BCBSNJ and its affiliates. The contents of this Medical Policy are not to be copied, reproduced or circulated to other parties without the express written consent of Horizon BCBSNJ. The contents of this Medical Policy may be updated or changed without notice, unless otherwise required by law and/or regulation. However, benefit determinations are made in the context of medical policies existing at the time of the decision and are not subject to later revision as the result of a change in medical policy
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