Print

Date Printed: June 26, 2017: 01:07 AM

Private Property of Blue Cross and Blue Shield of Florida.
This medical policy (medical coverage guideline) is Copyright 2017, Blue Cross and Blue Shield of Florida (BCBSF). All Rights Reserved. You may not copy or use this document or disclose its contents without the express written permission of BCBSF. The medical codes referenced in this document may be proprietary and owned by others. BCBSF makes no claim of ownership of such codes. Our use of such codes in this document is for explanation and guidance and should not be construed as a license for their use by you. Before utilizing the codes, please be sure that to the extent required, you have secured any appropriate licenses for such use. Current Procedural Terminology (CPT) is copyright 2017 American Medical Association. All Rights Reserved. No fee schedules, basic units, relative values, or related listings are included in CPT. The AMA assumes no liability for the data contained herein. Applicable FARS/DFARS restrictions apply to government use. CPT® is a trademark of the American Medical Association. 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.

09-J2000-00

Original Effective Date: 09/15/13

Reviewed: 09/14/16

Revised: 10/15/16

Next Review: 10/11/17

Subject: Dabrafenib (Tafinlar®) Capsules

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:

An estimated 50% of patients with metastatic melanoma have a mutation of the intracellular signaling kinase, BRAF. Targeted BRAF mutation therapies currently FDA-approved for the treatment of unresectable or metastatic melanoma which include vemurafenib, dabrafenib, trametinib, and cobimetinib.

Dabrafenib (Tafinlar), a kinase inhibitor that blocks BRAF protein, was approved by the U.S. Food and Drug Administration (FDA) on May 29, 2013 for the treatment of unresectable or metastatic melanoma in patients whose tumors express the BRAF V600E mutation. Mutations in the BRAF gene, including those that result in BRAF V600E, can result in stimulated tumor cell growth; therefore, dabrafenib is not indicated to treat wild-type BRAF melanoma.

The safety and efficacy of dabrafenib were evaluated in subjects with previously untreated, unresectable (Stage IIIc) or metastatic (Stage IV) melanoma determined to be BRAF V600E mutation positive in a randomized, open-label, active-controlled Phase III study (also known as BREAK-3). Subjects were randomized 3:1 to receive dabrafenib (dose: 150 mg by mouth) twice daily (n=187) or dacarbazine (dose: 1,000 mg/m2 IV) every three weeks (n=63). The primary endpoint was progression free survival, defined as the time from randomization until the earliest date of radiological disease progression or death from any cause.

The primary endpoint of progression free survival was statistically significant with a 69% reduction in the hazard rate of progression of disease or death with a hazard ratio of 0.33 (95% CI: 0.20, 0.55; p<0.001) in the dabrafenib group compared to the dacarbazine group. The median progression free survival was 5.1 months (95%CI: 4.9, 6.9) in the dabrafenib group compared to 2.7 months (95%CI: 1.5, 3.2) in the dacarbazine arm. The primary safety risk of dabrafenib was new primary malignancies; the rate of cutaneous squamous cell carcinoma was 11% in clinical trials. The most frequent (≥ 20%) adverse reactions of dabrafenib included hyperkeratosis, headache, and skin papilloma.

Targeted therapies have shown high initial response rates although about 50% of patients treated with monotherapy relapse around 6 months. An open-label, phase I/II trial was conducted in 247 patients to evaluate combination therapy with dabrafenib plus trametinib as compared to dabrafenib alone. Combination therapy resulted in an improved response rate as compared to monotherapy (76% vs 54%; p = 0.03). In addition, progression-free survival was also improved (9.4 vs 5.8 months; p <.001). The incidence of pyrexia was more common with the combination (76% vs 26%) although secondary squamous cell skin carcinoma was lower (7% vs 26%, respectively).

THxID BRAF Mutation Kit was approved with dabrafenib for use as a diagnostic assay to detect BRAF V600 (E or K) mutations in melanoma and to aid in the selection of patients for treatment with dabrafenib.

National Comprehensive Cancer Network (NCCN) Guidelines for Melanoma currently recommend dabrafenib for treatment of melanoma as a single agent or in combination with trametinib in patients with V600 mutation of the BRAF gene for unresectable and metastatic disease. In addition, NCCN recommends dabrafenib for the treatment of recurrent brain metastases due to melanoma and in non-small cell lung cancer (NSCLC) when the v600E BRAF gene is detected.

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.

I. Initiation of dabrafenib (Tafinlar) meets the definition of medical necessity for members diagnosed with ANY of the following conditions when ALL associated criteria are met:

1. Melanoma

a. Member is diagnosed with unresectable or metastatic melanoma

b. BRAF V600E or V600K mutation is detected by an FDA-approved test

c. Dabrafenib is used EITHER as monotherapy or in combination with trametinib (Mekinist)

d. Member meets one of the following:

1. Dabrafenib is used as first-line therapy (single agent or in combination with trametinib)

2. Dabrafenib is used as second-line or subsequent therapy if not previously used AND member’s performance status is 0-2 (single agent or in combination with trametinib)

e. Dose does not exceed 150 mg twice daily – dosage will be achieved using the fewest number of capsules per day

2. Recurrent brain metastases from metastatic melanoma

a. Dabrafenib is used as a single agent

b. Dabrafenib was active against the primary tumor (i.e., melanoma with BRAF V600 mutation)

c. Dose does not exceed 150 mg twice daily – dosage will be achieved using the fewest number of capsules per day

3. Non-small cell lung cancer (NSCLC) with BRAF V600E mutation

a. BRAF V600E mutation is detected by an FDA-approved test

b. Dabrafenib is used EITHER as monotherapy or in combination with trametinib (Mekinist)

c. Dose does not exceed 150 mg twice daily – dosage will be achieved using the fewest number of capsules per day

Duration of approval: 180 days

II. Dabrafenib (Tafinlar) meets the definition of medical necessity when used for the following designated Orphan Drug indications (http://www.fda.gov/orphan/designat/list.htm) when the dose does not exceed the maximum FDA-approved dose:

1. Treatment of malignant glioma with BRAF V600 mutation

Duration of approval: 180 days

III. Continuation of dabrafenib (Tafinlar) meets the definition of medical necessity for the treatment of melanoma, recurrent brain metastases from melanoma, NSCLC or malignant glioma when the following criteria are met:

1. The members disease has not progressed during treatment with dabrafenib

2. The member has been previously approved by Florida Blue or another health plan in the past 2 years, OR the member has previously met all indication-specific criteria for coverage

3. The dose does not exceed 150 mg twice daily and dosage will be achieved using the fewest number of capsules per day.

Duration of approval: 1 year

Dabrafenib (Tafinlar) is not considered a medical necessity for treatment of wild-type (i.e., normal) BRAF melanoma.

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

Unresectable or metastatic melanoma with BRAF V600E mutation: 150 mg orally twice daily, approximately 12 hours apart.

Confirm the presence of BRAF V600E mutation in tumor specimens prior to initiation of treatment.

Continue until disease progression or unacceptable toxicity occurs. Take at least 1 hour before or 2 hours after a meal. Do not take a missed dose within 6 hours of the next scheduled dose. Do not open, crush, or break dabrafenib.

Dose Adjustments

Refer to product label for management of treatment-related toxicity. Dosing may be reduced to 100 mg BID, then 75 mg BID, and lastly 50 mg BID. If unable to tolerate 50 mg BID, discontinue.

Drug Availability

50 mg, 75 mg capsules

PRECAUTIONS:

Boxed Warning

None

Contraindications

None

Precautions/Warnings

• New primary malignancies, cutaneous and non-cutaneous: Perform dermatologic evaluations prior to initiation of therapy, every 2 months while on therapy, and for up to 6 months following discontinuation

• Tumor Promotion in BRAF Wild-Type Melanoma: Increased cell proliferation can occur with BRAF inhibitors

• Hemorrhage: Major hemorrhagic events can occur in patients receiving dabrafenib in combination with trametinib. Monitor for signs and symptoms of bleeding.

• Venous Thromboembolism: Deep vein thrombosis and pulmonary embolism can occur.

• Cardiomyopathy: Assess LVEF before treatment with dabrafenib in combination with trametinib, after one month of treatment, then every 2 to 3 months thereafter.

• Ocular Toxicities: Perform ophthalmologic evaluation for any visual disturbances.

• Serious Febrile Reactions: Incidence and severity of pyrexia are increased with dabrafenib in combination with trametinib.

• Serious Skin Toxicity: Monitor for skin toxicities and for secondary infections. Discontinue for Common Terminology Criteria Adverse Events (CTCAE) intolerant Grade 2, or Grade 3 or 4 rash not improving within 3 weeks despite interruption of therapy.

• Hyperglycemia: Monitor serum glucose levels in patients with pre-existing diabetes or hyperglycemia

• Glucose-6-phosphate Dehydrogenase Deficiency: Closely monitor for hemolytic anemia.

• Embryofetal Toxicity: Can cause fetal harm. Advise females of reproductive potential of potential risk to a fetus; dabrafenib may render hormonal contraceptives less effective and an alternative method of contraception should be used

BILLING/CODING INFORMATION:

The following codes may be used to describe:

HCPCS Coding:

C9399

Unclassified drugs or biologicals

J8999

Prescription drug, oral, chemotherapeutic, Not Otherwise Specified

ICD-10 Diagnoses Codes That Support Medical Necessity: (Effective 10/01/15)

C33

Malignant neoplasm of trachea

C34.00 – C34.02

Malignant neoplasm of unspecified main bronchus

C34.10 – C34.12

Malignant neoplasm of upper lobe, unspecified bronchus or lung

C34.2

Malignant neoplasm of middle lobe, unspecified bronchus or lung

C34.30 – C34.32

Malignant neoplasm of lower lobe, unspecified bronchus or lung

C34.80 – C34.82

Malignant neoplasm of overlapping sites of unspecified bronchus and lung

C34.90 – C34.92

Malignant neoplasm of unspecified part of unspecified bronchus or lung

C43.0

Malignant melanoma of lip

C43.10

Malignant melanoma of unspecified eyelid, including canthus

C43.11

Malignant melanoma of right eyelid, including canthus

C43.12

Malignant melanoma of left eyelid, including canthus

C43.20

Malignant melanoma of unspecified ear and external auricular canal

C43.21

Malignant melanoma of right ear and external auricular canal

C43.22

Malignant melanoma of left ear and external auricular canal

C43.30

Malignant melanoma of unspecified part of face

C43.31

Malignant melanoma of nose

C43.39

Malignant melanoma of other parts of face

C43.4

Malignant melanoma of scalp and neck

C43.51

Malignant melanoma of anal skin

C43.52

Malignant melanoma of skin of breast

C43.59

Malignant melanoma of other part of trunk

C43.60

Malignant melanoma of unspecified upper limb, including shoulder

C43.61

Malignant melanoma of right upper limb, including shoulder

C43.62

Malignant melanoma of left upper limb, including shoulder

C43.70

Malignant melanoma of unspecified lower limb, including hip

C43.71

Malignant melanoma of right lower limb, including hip

C43.72

Malignant melanoma of left lower limb, including hip

C43.8

Malignant melanoma of overlapping sites of skin

C43.9

Malignant melanoma of skin, unspecified

C79.31

Secondary malignant neoplasm of brain

C80.0

Disseminated malignant neoplasm, unspecified

C80.1

Malignant (primary) neoplasm, unspecified

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: BCBSF 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:

Table 1: Eastern Cooperative Oncology Group (ECOG) Performance Status

Grade

Description

0

Fully active, able to carry on all pre-disease performance without restriction

1

Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, e.g., light house work, office work

2

Ambulatory and capable of all self-care but unable to carry out any work activities. Up and about more than 50% of waking hours

3

Capable of only limited self-care, confined to bed or chair more than 50% of waking hours

4

Completely disabled. Cannot carry on any self-care. Totally confined to bed or chair

5

Dead

RELATED GUIDELINES:

Trametinib (Mekinist™) Tablets - 09-J1000-99

OTHER:

Table 2: Common Terminology Criteria for Adverse Events v4.0 (CTCAE)

Grade

Description

1

Mild; asymptomatic or mild symptoms; clinical diagnostic observations only; intervention not indicated

2

Moderate; minimal, local or noninvasive intervention indicated; limited age-appropriate instrumental activities of daily living

3

Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self-care activities of daily living

4

Life-threatening consequences; urgent intervention indicated

5

Death related to adverse event

REFERENCES:

  1. American Cancer Society: Cancer Facts and Figures 2015. Available at http://www.cancer.org/acs/groups/content/@editorial/documents/document/acspc-044552.pdf. Accessed Sept 24, 2015.
  2. AHFS Drug Information. Bethesda (MD): American Society of Health-System Pharmacists, Inc; 2016 [cited 2016 Aug 25]. In: STAT!Ref Online Electronic Medical Library [Internet]. Available from: http://online.statref.com/.
  3. Clinical Pharmacology [Internet]. Tampa (FL): Gold Standard, Inc.; 2015 [cited 2016 Aug 25]. Available from: http://www.clinicalpharmacology.com/.
  4. ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine; 2000 Feb 29 - [cited 2016 Aug 25]. Available from: http://clinicaltrials.gov/.
  5. DRUGDEX® System [Internet]. Greenwood Village (CO): Thomson Micromedex; Updated periodically [cited 2016 Aug 25]. Available from: http://www.thomsonhc.com/.
  6. National Cancer Institute. Common Terminology Criteria for Adverse Events. Available at: http://evs.nci.nih.gov/ftp1/CTCAE/CTCAE_4.03_2010-06-14_QuickReference_8.5x11.pdf. Accessed 9/24/15.
  7. National Comprehensive Cancer Network (NCCN). Clinical practice guidelines in oncology. Version 1.2016. Central Nervous System Cancers. Available at http://www.nccn.org/professionals/physician_gls/PDF/cns.pdf. Accessed 8/30/16
  8. National Comprehensive Cancer Network (NCCN). Clinical practice guidelines in oncology. Version 3.2016. Melanoma. Available at http://www.nccn.org/professionals/physician_gls/PDF/melanoma.pdf. Accessed 08/25/16.
  9. National Comprehensive Cancer Network (NCCN). Clinical practice guidelines in oncology. Version 4.2016. Non-Small Cell Lung Cancer. Available at http://www.nccn.org/professionals/physician_gls/pdf/nscl.pdf. Accessed 8/30/16.
  10. National Comprehensive Cancer Network (NCCN). Drugs & Biologics Compendium [Internet]. Fort Washington (PA): National Comprehensive Cancer Network; 2016 [cited 2016 Aug 25]. Available from: http://www.nccn.org/professionals/drug_compendium/content/contents.asp/.
  11. Orphan Drug Designations and Approval [Internet]. Silver Spring (MD): US Food and Drug Administration; 2016 [cited 2016 Aug 25]. Available from: http://www.accessdata.fda.gov/scripts/opdlisting/oopd/index.cfm/.
  12. Tafinlar (dabrafenib) capsule [package insert]. GlaxoSmithKline LLC. Research Triangle Park, NC. November 2015.

COMMITTEE APPROVAL:

This Medical Coverage Guideline (MCG) was approved by the BCBSF Pharmacy Policy Committee on 09/14/16

GUIDELINE UPDATE INFORMATION:

09/15/13

New Medical Coverage Guideline.

11/15/14

Review and revision to guideline; consisting of position statement, coding, references.

08/15/15

Revision to guidelines; consisting of position statement, coding.

09/15/15

Revision to guidelines; consisting of position statement.

11/15/15

Revision to guidelines; consisting of updating position statement, description, dosing/administration, warnings/precautions, definitions, coding and references.

12/15/15

Revision to guideline; consisting of updating position statement and references.

10/15/16

Revision to guideline; consisting of updating position statement, description, coding and references

Date Printed: June 26, 2017: 01:07 AM