Medical Drug Criteria (MDC)

Policy Num:       P1.002.033
Policy Name:     Gefitinib
Policy ID:          [P1.002.033] [Ac/L/ M+/ P+] [0.00.00]

Last Review:       September 22, 2025
Next Review:      September 20, 2026
 

Related MCD: None

Gefitinib (Iressa^TM)

Summary

Gefitinib (Iressa®) is an orally administered tyrosine kinase inhibitor (TKI) of the epidermal growth factor receptor (EGFR). It is FDA-approved 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.

objective

Define the criteria for coverage and medical necessity of Gefitinib for the treatment of patients with EGFR-mutated NSCLC, according to FDA labeling, NCCN Guidelines, and CMS guidance.

Policy Statements

1. Gefitinib is medically necessary when ALL of the following are met:

Patient is ≥18 years of age.

Diagnosis of metastatic non-small cell lung cancer (NSCLC).

Documentation of EGFR exon 19 deletion or exon 21 (L858R) mutation, confirmed by an FDA-approved test.

Gefitinib is prescribed as first-line therapy.

2. Gefitinib is considered experimental/investigational and not covered for all other indications, including use in patients without documented EGFR mutations.

Policy Guidelines

Pre - PA Allowance

None

Prior - Approval Limits

Quantity 90 tablets per 90 days

Duration 12 months

DOSAGE/ADMINISTRATION

Recommended dose is 250 mg orally, once daily with or without food. 
 

REQUIRED MEDICAL INFORMATION

Prior-Approval Requirements

Age 18 years of age or older

Diagnosis

Patient must have the following:

1. Metastatic non-small cell lung cancer

a. Tumors must have epidermal growth factor receptor (EGFR) exon 19 deletions or exon 21 (L858R) substitution mutations detected by an FDA-approved test

AND NONE of the following:

1. Confirmed interstitial lung disease (ILD)

2. Severe hepatic impairment (Child-Pugh Class C)

AND the following:

1. Physician agrees to withhold or discontinue the therapy if patient develops the following:

a. Grade 2 or higher for ALT and/or AST elevations

b. Worsening signs of respiratory symptoms

c. Persistent ulcerative keratitis of eye

d. Gastrointestinal perforation

Prior – Approval Renewal Requirements

Age 18 years of age or older

Diagnosis

Patient must have the following:

1. Metastatic non-small cell lung cancer

a. NO disease progression or unacceptable toxicity

AND NONE of the following has developed:

1. Confirmed interstitial lung disease (ILD)

2. Severe hepatic impairment (Child-Pugh Class C)

3. Gastrointestinal perforation

4. Persistent ulcerative keratitis of eye

AND the following:

1. Physician agrees to withhold or discontinue the therapy if patient develops the following:

a. Grade 2 or higher for ALT and/or AST elevations

b. Worsening signs of respiratory symptoms

EXCLUSION CRITERIA

None

BENEFIT APPLICATION

Coverage is subject to the patient’s benefit plan.
 
Prior authorization is required.
 
Off-label use will require peer-review medical director evaluation.

Regulatory Status

FDA Approval: Gefitinib (Iressa®) received accelerated FDA approval in 2003, withdrawn in 2012, and re-approved in 2015 for EGFR mutation-positive NSCLC.
 
CMS/Medicare: Coverage is consistent with FDA labeling and NCCN guidelines.

Practice Guidelines and Position Statements

NCCN Guidelines (v.2025): Recommend gefitinib as a first-line option for EGFR exon 19 deletion or exon 21 L858R NSCLC.

ASCO Guidelines: Support EGFR-TKI as initial therapy for EGFR-mutant NSCLC.

Medicare National Coverage

No National Coverage Determination (NCD). Local Coverage Determinations (LCDs) generally align with NCCN and FDA labeling.

References

1. Iressa [package insert]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; February 2023.

2. NCCN Drugs & Biologics Compendium® Gefitinib 2024. National Comprehensive Cancer Network, Inc. Accessed on October 28, 2024.

3. FDA. Gefitinib (Iressa®) Prescribing Information. 2015, updated 2024.

4. NCCN Clinical Practice Guidelines in Oncology: Non-Small Cell Lung Cancer. Version 2025.

5. Mok TS, et al. Gefitinib or carboplatin–paclitaxel in pulmonary adenocarcinoma. NEJM. 2009.

6. CMS LCDs for Oncology Biomarker Testing.

Codes

Applicable Modifiers

Policy History