09-J2000-44 Original Effective Date: 09/15/15 Reviewed: 09/12/18 Revised: 10/15/18 Subject: Gefitinib (Iressa) THIS MEDICAL COVERAGE GUIDELINE IS NOT AN AUTHORIZATION, CERTIFICATION, EXPLANATION OF BENEFITS, OR A GUARANTEE OF PAYMENT, NOR DOES IT SUBSTITUTE FOR OR CONSTITUTE MEDICAL ADVICE. ALL MEDICAL DECISIONS ARE SOLELY THE RESPONSIBILITY OF THE PATIENT AND PHYSICIAN. BENEFITS ARE DETERMINED BY THE GROUP CONTRACT, MEMBER BENEFIT BOOKLET, AND/OR INDIVIDUAL SUBSCRIBER CERTIFICATE IN EFFECT AT THE TIME SERVICES WERE RENDERED. THIS MEDICAL COVERAGE GUIDELINE APPLIES TO ALL LINES OF BUSINESS UNLESS OTHERWISE NOTED IN THE PROGRAM EXCEPTIONS SECTION. Dosage/ Administration Position Statement Billing/Coding Reimbursement Program Exceptions Definitions Related Guidelines Other References Updates DESCRIPTION: Gefitinib (Iressa), an oral selective epidermal growth factor receptor (EGFR)-inhibitor, was approved by the U.S. Food and Drug Administration (FDA) in July 2015 for the first-line treatment of patients with metastatic non-small cell lung cancer (NSCLC) whose tumors have EGFR exon 19 deletions or exon 21 (L858R) substitution mutations as detected by an FDA-approved test. Efficacy has not been established in patients with whose tumors have other EGFR mutations. The efficacy and safety of gefitinib for the first-line treatment of patients with metastatic NSCLC containing EGFR exon 19 deletions or L858R substitution mutations was demonstrated in a multicenter, single-arm, open-label clinical study (Study 1). A total of 106 treatment-naive patients with metastatic EGFR mutation positive NSCLC received gefitinib 250 mg once daily until disease progression or intolerable toxicity. The major efficacy outcome measure was objective response rate (ORR) according to RECIST v1.1 as evaluated by both blinded independent review and investigators. Duration of response (DOR) was an additional outcome measure. Eligible patients were required to have a deletion in EGFR exon 19 or L858R, L861Q, or G719X substitution mutation and no T790M or S768I mutation or exon 20 insertion in tumor specimens as prospectively determined by a clinical trial assay. Tumor samples from 87 patients were tested retrospectively using the therascreen EGFR RGQ PCR Kit. Sixty patients had exon 19 deletions (65%), 29
patients had L858R substitution (31%), while two patients each had tumors harboring L861Q or G719X substitution mutation. The median duration of treatment was 8.0 months. Efficacy results from Study 1 are summarized below: Efficacy Parameter Blinded Independent Assessment (n=106) Investigator Assessment (n=106) ORR (95% CI) 50% (41, 59) 70% (61, 78) Complete Response Rate 0.9% 1.9% Median DOR (months) (95% CI) 6.0 (5.6, 11.1) 8.3 (7.6, 11.3) The response rates were similar in patients whose tumors had EGFR exon 19 deletions and exon 21 L858R substitution mutations. Two partial responses were observed in both patients whose tumors had G719X substitution mutation with duration of response of at least 2.8 months and 5.6 months, respectively. One of two patients whose tumors had L861Q substitution mutation also achieved a partial response with duration of response of at least 2.8 months. National Comprehensive Cancer Network (NCCN) Guidelines for Non-Small Cell Lung Cancer (Version 6.2018) recommend gefitinib be used in EGFR mutation positive NSCLC. POSITION STATEMENT: Comparative Effectiveness The Food and Drug Administration has deemed the drug(s) or biological product(s) in this coverage policy to be appropriate for self-administration or administration by a caregiver (i.e., not a healthcare professional). Therefore, coverage (i.e., administration) in a provider-administered setting such as an outpatient hospital, ambulatory surgical suite, physician office, or emergency facility is not considered medically necessary. Initiation of gefitinib (Iressa) meets the definition of medical necessity when ALL of the following criteria are met: 1. Member is diagnosed with non-small cell lung cancer (NSCLC) 2. Member s disease is recurrent or metastatic 3. Member has a documented epidermal growth factor receptor (EGFR) mutation laboratory documentation must be provided
4. Gefitinib will be used as monotherapy (without concomitant chemotherapy) 5. Dose does not exceed 250 mg daily with the following exception: a. Dose does not exceed 500 mg daily AND member is receiving a concomitant strong CYP3A4 enzyme inducer (e.g., carbamazepine, dexamethasone, phenobarbital, phenytoin, rifabutin, rifampin, rifapentin) 6. Member is age 18 years or older Approval duration: 6 months Continuation of gefitinib (Iressa) meets the definition of medical necessity when ALL of the following criteria are met: 1. Member was previously approved by Florida Blue or another health plan in the past 2 years for the treatment of NSCLC with an EGFR mutation, OR the member previously met ALL indicationspecific initiation criteria 2. Gefitinib will be used as monotherapy (without concomitant chemotherapy) 3. Dose does not exceed 250 mg daily with the following exception: a. Dose does not exceed 500 mg daily AND member is receiving a concomitant strong CYP3A4 enzyme inducer (e.g., carbamazepine, dexamethasone, phenobarbital, phenytoin, rifabutin, rifampin, rifapentin) 4. Member is age 18 years or older Approval duration: 1 year DOSAGE/ADMINISTRATION: THIS INFORMATION IS PROVIDED FOR INFORMATIONAL PURPOSES ONLY AND SHOULD NOT BE USED AS A SOURCE FOR MAKING PRESCRIBING OR OTHER MEDICAL DETERMINATIONS. PROVIDERS SHOULD REFER TO THE MANUFACTURER S FULL PRESCRIBING INFORMATION FOR DOSAGE GUIDELINES AND OTHER INFORMATION RELATED TO THIS MEDICATION BEFORE MAKING ANY CLINICAL DECISIONS REGARDING ITS USAGE. FDA-approved 250 mg orally, once daily with or without food Dose Adjustments Strong CYP3A4 Inducers: Increase gefitinib to 500 mg daily in the absence of severe adverse drug reaction, and resume at 250 mg seven days after discontinuation of the strong CYP3A4 inducer Recommendations for dose modifications due to adverse reactions are provided in FDAapproved Prescribing Information Drug Availability
Tablets: 250 mg PRECAUTIONS: Boxed Warning Contraindications Precautions/Warnings Interstitial lung disease Hepatotoxicity: Obtain periodic liver function testing Gastrointestinal perforation Diarrhea Ocular disorders including keratitis Bullous and exfoliative skin disorders Embryo-fetal toxicity BILLING/CODING INFORMATION: The following codes may be used to describe: HCPCS Coding J8565 Gefitinib, oral, 250 mg ICD-10 Diagnosis Codes That Support Medical Necessity C33 Malignant neoplasm of trachea C34.0 Malignant neoplasm of main bronchus C34.00 Malignant neoplasm of unspecified main bronchus C34.01 Malignant neoplasm of right main bronchus C34.02 Malignant neoplasm of left main bronchus C34.1 Malignant neoplasm of upper lobe, bronchus or lung
C34.10 Malignant neoplasm of upper lobe, unspecified bronchus or lung C34.11 Malignant neoplasm of upper lobe, right bronchus or lung C34.12 Malignant neoplasm of upper lobe, left bronchus or lung C34.2 Malignant neoplasm of middle lobe, bronchus or lung C34.3 Malignant neoplasm of lower lobe, bronchus or lung C34.30 Malignant neoplasm of lower lobe, unspecified bronchus or lung C34.31 Malignant neoplasm of lower lobe, right bronchus or lung C34.32 Malignant neoplasm of lower lobe, left bronchus or lung C34.8 Malignant neoplasm of overlapping sites of bronchus and lung C34.80 Malignant neoplasm of overlapping sites of unspecified bronchus and lung C34.81 Malignant neoplasm of overlapping sites of right bronchus and lung C34.82 Malignant neoplasm of overlapping sites of left bronchus and lung C34.9 Malignant neoplasm of unspecified part of bronchus or lung C34.90 Malignant neoplasm of unspecified part of unspecified bronchus or lung C34.91 Malignant neoplasm of unspecified part of right bronchus or lung C34.92 Malignant neoplasm of unspecified part of left bronchus or lung C79.31 Secondary malignant neoplasm of brain REIMBURSEMENT INFORMATION: Refer to section entitled POSITION STATEMENT. PROGRAM EXCEPTIONS: Federal Employee Program (FEP): Follow FEP guidelines.
State Account Organization (SAO): Follow SAO guidelines. Medicare Part D: Florida Blue has delegated to Prime Therapeutics authority to make coverage determinations for the Medicare Part D services referenced in this guideline. Medicare Advantage: No National Coverage Determination (NCD) and/or Local Coverage Determination (LCD) were found at the time of the last guideline revised date. DEFINITIONS: RELATED GUIDELINES: OTHER: REFERENCES: 1. AstraZeneca. Iressa (gefitinib) tablet, coated. 2018 [cited 8/28/18]. In: DailyMed [Internet]. Bethesda (MD): National Library of Medicine. Available from: http://dailymed.nlm.nih.gov/dailymed/druginfo.cfm?setid=827d60e8-7e07-41b7-c28b- 49ef1c4a5a41#section-1/. 2. Clinical Pharmacology [Internet]. Tampa (FL): Gold Standard, Inc.; 2018 [cited 8/28/18]. Available from: http://www.clinicalpharmacology.com/. 3. ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine; 2000 Feb 29 - [cited 8/28/18]. Available from: http://clinicaltrials.gov/. 4. DRUGDEX System [Internet]. Greenwood Village (CO): Thomson Micromedex; Updated periodically [cited 8/28/18]. Available from: http://www.thomsonhc.com/. 5. National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology (NCCN Guidelines ). Non-small cell lung cancer, v. 2.2018 [cited 2/14/18]. Available from: http://www.nccn.org/professionals/physician_gls/f_guidelines.asp. 6. Orphan Drug Designations and Approval [Internet]. Silver Spring (MD): US Food and Drug Administration; 2018 [cited 8/28/18]. Available from: http://www.accessdata.fda.gov/scripts/opdlisting/oopd/index.cfm/. COMMITTEE APPROVAL: This Medical Coverage Guideline (MCG) was approved by the Florida Blue Pharmacy Policy Committee on 9/12/18. GUIDELINE UPDATE INFORMATION: 09/15/15 New Medical Coverage Guideline.
11/01/15 Revision: ICD-9 Codes deleted. 09/15/16 Review and revision to guideline, consisting of updating position statement and references. 10/15/17 Review and revision to guideline, consisting of updating position statement and references. 03/15/18 Revision to guidline, consisting of adding NCCN updates to position statement. 10/15/18 Review and revision to guideline, consisting of updating position statement and references.