Subject: Vandetanib (Caprelsa ) Tablets

Transcription

1 09-J Original Effective Date: 10/15/11 Reviewed: 11/14/18 Revised: 12/15/18 Subject: Vandetanib (Caprelsa ) Tablets 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. Position Statement Dosage/Administratio n Billing/Coding Reimbursement Program Exceptions Definitions Related Guidelines Other References Updates DESCRIPTION: The main histologic types of thyroid cancer include differentiated (papillary, follicular, and Hurthle cell), medullary, and anaplastic. Medullary thyroid carcinoma (MTC) is a malignancy of the parafollicular C cells of the thyroid gland. Neither radiotherapy nor chemotherapy has demonstrated durable objective responses in persons with advanced MTC. Evidence from preclinical studies of molecular targeted therapeutics with activity against rearranged during transfection (RET) proto-oncogene demonstrate that RET kinase is a potential therapeutic target in MTC. Other signaling pathways likely to contribute to the growth and invasiveness of MTC include vascular endothelial growth factor receptor (VEGFR)-dependent tumor angiogenesis and epidermal growth factor receptor (EGFR)-dependent tumor cell proliferation. Vandetanib (Caprelsa ) is a novel small-molecule kinase inhibitor. In vitro studies have shown that vandetanib inhibits the activity of multiple tyrosine kinases, including members of the epidermal growth factor receptor (EGFR) family, vascular endothelial growth factor (VEGF) receptors, RET, protein tyrosine kinase 6, TIE2, members of the EPH receptors kinase family, and members of the Src family of tyrosine kinases. Vandetanib inhibits endothelial cell migration, proliferation, and survival and new blood vessel formation in in vitro models of angiogenesis. Vandetanib inhibits EGFR-dependent cell survival in vitro. In addition, vandetanib inhibits epidermal growth factor stimulated receptor tyrosine kinase phosphorylation in tumor cells and endothelial cells and VEGF-stimulated tyrosine kinase phosphorylation in endothelial cells. Vandetanib was evaluated in a double-blind, randomized trial of 331 patients with unresectable, locally advanced or metastatic MTC. In comparison to placebo, vandetanib increased progression free survival (hazard ratio 0.35, 95% CI ). The FDA approved vandetanib for the treatment of symptomatic or progressive MTC in patients with unresectable locally advanced or metastatic disease through a restricted access program due to the potential for cardiac toxicity.

2 National Comprehensive Cancer Network (NCCN) Guidelines for Thyroid cancer currently recommend vandetanib for both MTC and differentiated thyroid cancers (papillary, follicular, and Hurthle cell). Of note, NCCN states that several factors should be considered prior to initiating therapy with a kinase inhibitor which includes the following: therapy may improve progression-free survival but is not curative, side effects may have a significant effect on quality of life, rates of disease progression are variable, and the pace of disease progression should be factored into treatment decisions. More specifically, patients with indolent disease who are asymptomatic may not be appropriate for kinase inhibitors due to side effects adversely affecting the patient s quality of life whereas patients with rapidly progressing disease may experience benefit even in the presence of side effects. Vandetanib is also recommended by NCCN for the treatment of non-small cell lung cancer when positive for RET gene rearrangements. 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 vandetanib (Caprelsa ) meets the definition of medical necessity when administered for the indications listed in Table 1 and ALL of the indication-specific criteria are met: Table 1 Indications Specific Criteria Non-small cell lung cancer ALL of the following are met: 1. Member has tested positive for RET gene rearrangements 2. Vandetanib is used as a single agent 3. Dose does not exceed 300 mg/day using the fewest number of tablets per day Medullary thyroid carcinoma ALL of the following are met: 1. Member s disease is progressive and/or symptomatic 2. Member has ONE of the following: a. Unresectable locoregional disease b. Distant metastatic disease 3. Vandetanib is used as a single agent 4. Dose does not exceed 300 mg/day using the fewest number of tablets per day

3 Follicular carcinoma Hurthle cell carcinoma Papillary carcinoma ALL of the following are met: 1. Member s disease is progressive and/or symptomatic 2. Member has ONE of the following: a. Unresectable locoregional disease that is recurrent or persistent b. Distant metastatic disease 3. Member s disease is resistant to radioiodine treatment 4. Vandetanib is used as a single agent 5. Dose does not exceed 300 mg/day using the fewest number of tablets per day Approval duration: 180 days II. Vandetanib (Caprelsa ) meets the definition of medical necessity when used as a single agent for the following designated Orphan Drug indication ( when the dose does not exceed the maximum FDA-approved dosing: a. Anaplastic thyroid cancer Approval duration: 1 year III. Continuation of vandetanib (Caprelsa ) meets the definition of medical necessity for the indications in Table I and orphan indications when ALL of the following criteria are met: A. The member s disease has not progressed while receiving treatment with vandetanib B. 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 C. The dose does not exceed 300 mg per day and will be achieved using the fewest number of tablets per day. 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: Vandetanib is approved for the treatment of adult members with symptomatic or progressive medullary thyroid carcinoma with unresectable locally advanced or metastatic disease. The use of vandetanib in the treatment of indolent, asymptomatic or slowly progressing disease should be carefully considered because of the treatment related risk of vandetanib.

4 Vandetanib 300 mg should be taken once daily, with or without food. Vandetanib tablets should be swallowed intact and should not be crushed. Vandetanib therapy should be continued until members are no longer benefiting from treatment or an unacceptable toxicity occurs. Recommended Dose Adjustments: Corrected QT interval (corrected for heart rate using Fridericia s formula [QTcF]) exceeds 500 ms: interrupt dosing until toxicity returns to less than 450 ms, then resume at a reduced dose Common Terminology Criteria for Adverse Events (CTCAE) grade 3 or greater toxicity: interrupt dosing until toxicity resolves to CTCAE grade 1, and then resume at a reduced dose. The 300 mg daily dose can be reduced to 200 mg (two 100 mg tablets) and then to 100 mg for CTCAE grade 3 or greater toxicities. Note: Because of the 19-day half-life, adverse reactions, including a prolonged QT interval, may not resolve quickly. Monitor appropriately. Moderate (creatinine clearance [CrCl] ml/min) and severe renal impairment (CrCl < 30 ml/min): reduce the starting dose to 200 mg (two 100 mg tablets) daily. Hepatic Impairment: vandetanib was not studied in members with moderate (Child-Pugh class B) and severe (Child-Pugh class C) hepatic insufficiency and should be avoided in this member population. Missed Dose: If a member misses a dose, the missed dose should not be taken if it is less than 12 hours before the next dose. Drug Availability: Vandetanib is available as 100- and 300 mg film-coated tablets. Vandetanib is not available at retail pharmacies and can only be dispensed through a restricted distribution program. CONTRAINDICATIONS Vandetanib is contraindicated in members with congenital long QT syndrome. PRECAUTIONS/ WARNINGS: Boxed Warning Vandetanib can prolong the QT interval. Torsades de pointes and sudden death have occurred. Use should be avoided in persons with hypocalcemia, hypokalemia, hypomagnesemia, or long QT syndrome. Avoid use in combination with agents known to prolong the QT interval. Warnings Prolonged QT Interval, Torsades de pointes, ventricular tachycardia and sudden death: Monitor electrocardiograms and levels of serum potassium, calcium, magnesium and TSH. Reduce vandetanib dose as appropriate. Do not initiate treatment if the QTcF interval is greater than 450 ms. Severe skin reactions, including Stevens-Johnson syndrome, some resulting in death: Consider discontinuation of vandetanib for severe skin reactions. Photosensitivity can occur up during treatment and up to 4 months after treatment discontinuation. Interstitial lung disease (ILD) or pneumonitis, including fatalities: investigate unexplained nonspecific respiratory signs and symptoms. Discontinue vandetanib for confirmed ILD. Ischemic cerebrovascular events, hemorrhage, heart failure, diarrhea, hypertension, and reversible posterior leukoencephalopathy syndrome: Discontinue or interrupt vandetanib.

5 Hypothyroidism may occur: monitor TSH during treatment. Embryo-fetal toxicity: Can cause fetal harm. Advise women of the potential risk to a fetus and to avoid pregnancy during and for four months following treatment with vandetanib. Vandetanib Risk Evaluation and Mitigation Strategy (REMS) Program: A REMS is required for vandetanib due to the risk of QT prolongation, Torsades de pointes, and sudden death. Vandetanib is available only through the restricted distribution program called CAPRELSA REMS Program. The program requires prescribers and pharmacies to be certified to prescribed and dispense vandetanib. For more information about the specific REMS requirements or to enroll in the CAPRELSA REMS program, visit or call BILLING/CODING INFORMATION: HCPCS Coding: C9399 Unclassified drugs or biologicals. J8999 Prescription drug, oral, chemotherapeutic, NOS ICD-10 Diagnosis Codes That Support Medical Necessity: 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, 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 C73 Malignant neoplasm of thyroid gland REIMBURSEMENT INFORMATION: Refer to section entitled POSITION STATEMENT. PROGRAM EXCEPTIONS: Federal Employee Program (FEP): Follow FEP guidelines.

6 State Account Organization (SAO): Follow SAO guidelines. Medicare Advantage products: No National Coverage Determination (NCD) and/or Local Coverage Determination (LCD) were found at the time of the last guideline revised date. 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. DEFINITIONS: Medullary thyroid carcinoma (MTC): A form of thyroid carcinoma which originates from the parafollicular cells (C cells), which produce the hormone calcitonin. RELATED GUIDELINES: Cabozantinib (Cometriq ), 09-J OTHER: Table 1: 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. 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: 2. American Cancer Society: Cancer Facts and Figures Available at Accessed Sept 24, Caprelsa (vandetanib) [package insert]. AstraZeneca Pharmaceuticals LP. Wilmington (DE): July 2016.

7 4. Clinical Pharmacology. [database online]. Tampa, FL: Gold Standard, Inc.; URL: Accessed 10/29/ Food and Drug Administration. Center for Drug Evaluation and Research: Application number : Summary review. Accessed 08/09/ Micromedex Healthcare Series [Internet database]. Greenwood Village, Colorado: Thomson Healthcare. Updated periodically. Accessed 10/29/ Ingenix HCPCS Level II, Expert Ingenix ICD-9-CM for Physicians-Volumes 1 & 2, Expert Kloos RT, Eng C, Evans DB, et al. Medullary thyroid cancer: management guidelines of the American Thyroid Association. Thyroid 2009;19(6): National Cancer Institute. Common Terminology Criteria for Adverse Events. Available at: Accessed 9/24/ National Comprehensive Cancer Network (NCCN). Clinical practice guidelines in oncology. Version Non-small cell lung cancer. Available at Accessed 10/29/ National Comprehensive Cancer Network (NCCN). Clinical practice guidelines in oncology. Version Thyroid Carcinoma. Available at Accessed 10/29/ National Comprehensive Cancer Network (NCCN). Drugs & Biologics Compendium [Internet]. Fort Washington (PA): National Comprehensive Cancer Network; 2018 [cited 2018 Oct 29]. Available from: Orphan Drug Designations and Approval [Internet]. Silver Spring (MD): US Food and Drug Administration; 2018 [cited 2018 Oct 29]. Available from: Wells SA, Robinson BG, Gagel RF. Vandetanib in members with locally advanced or metastatic medullary thyroid cancer: a randomized, double-blind, Phase III trial. J Clin Oncol. 2012; 30: Wells SA, Sylvia LA, Henning D et al. Revised American Thyroid Association guidelines for the management of medullary thyroid carcinoma. Thyroid. 2015; 25: COMMITTEE APPROVAL: This Medical Coverage Guideline (MCG) was approved by the Florida Blue Pharmacy Policy Committee on 11/14/18. GUIDELINE UPDATE INFORMATION: 10/15/11 New Medical Coverage Guideline. 10/15/12 Review and revision to guideline; consisting of revising position statement, dosage and administration, and precautions sections; updating reference section; and adding contraindication. 11/15/13 Review and revision to guideline; consisting of updating references and program exceptions.

8 11/15/14 Review and revision to guideline; consisting of revising position statement and precautions section; updating references. 11/01/15 Revision: ICD-9 Codes deleted. 11/15/15 Review and revision to guideline; consisting of revising position statement, dosing/administration, warnings/precautions, coding and references. 10/15/16 Review and revision to guideline; consisting of revising position statement, description and references. 12/15/17 Review and revision to guideline; consisting of revising position statement, description, coding and references. 12/15/18 Review and revision to guideline; consisting of updating references.