Plus Medicare Part D Formulary Prior Authorization …...cancer chemotherapeutic regimen within 48 hours of the patient receiving cancer treatment is billed under Part B. The assumption

Plus Medicare Part D Formulary Prior Authorization Guidelines

PLUS DRUG FORMULARY

PRIOR AUTHORIZATION GUIDELINES

Copyright © 2004-2016 MedImpact, Inc. All rights reserved. This document is confidential and proprietary to MedImpact and contains material MedImpact may consider Trade Secrets. This document is intended for specified use by Business Partners of MedImpact under permission by MedImpact and may not otherwise be reproduced, transmitted, published, or disclosed to others without prior written authorization. MedImpact maintains the sole and exclusive ownership, right, title, and interest in and to this document.

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FOREWORD This document will serve as a reference to assist with administration of clinical and administrative prior authorization (PA) criteria for Part D Standard formulary clients. This document should not be used to determine formulary status or effective date for a PA guideline. To determine formulary status or effective date for a PA guideline, refer to the formulary ASCII and PA ASCII files produced monthly.

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5HT3 ANTI-NAUSEA AGENT BVD DETERMINATION (PART D)

Generic Brand HICL GCN Exception/Other

ONDANSETRON HCL ZOFRAN 06055 ROUTE = ORAL

ONDANSETRON ZOFRAN ODT, ZUPLENZ

19058

GRANISETRON KYTRIL, GRANISOL

07611 ROUTE = ORAL

DOLASETRON ANZEMET 16576 ROUTE = ORAL

Do not review Part D guidelines with physicians; if the caller wishes to initiate an oral request then a verbal MRF must be completed. Please check the applicable CS note for processing. NOTE: This PA is for administrative purposes to determine Medicare Part B versus Medicare Part D funding and applies to ORAL forms of these agents only. GUIDELINES FOR USE 1. Is the prescription written for greater than a 2 days (48 hours) supply?

If yes, continue to #3. If no, continue to #2.

2. Is the prescription written for a full therapeutic replacement for an intravenous anti-emetic drug as part of a cancer chemotherapeutic regimen for use within 48 hours of the patient receiving cancer treatment? (CSR: If unknown, ask the caller to submit MRF.)

If yes, approve for 12 months under Part B. (Populate the B vs. D field with "B" in the PA override field. If MI does not process Part B for the client, refer the caller/request back to the Health plan.) If no, continue to #3.

3. Approve for up to 12 months under Part D. (Populate B vs. D field with "D" in the PA override field.)

RATIONALE Ensure that any use as a full therapeutic replacement for an intravenous anti-emetic drug as part of a cancer chemotherapeutic regimen within 48 hours of the patient receiving cancer treatment is billed under Part B. The assumption is that any prescription that exceeds a 2 days supply is by default not intended to specifically comply with the Medicare Part B requirement for Part B coverage of antiemetics, and therefore should be covered under Part D, irrespective of the timing relative to chemo (i.e. even if the prescription is filled within 48 hours of chemo).

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5HT3 ANTI-NAUSEA AGENT BVD DETERMINATION (PART D) FDA APPROVED INDICATIONS The ORAL FORM OF ZOFRAN and ORAL SOLUBLE FILM ZUPLENZ are indicated for the prevention of nausea and vomiting associated with highly emetogenic cancer chemotherapy, including cisplatin ≥ 50 mg/m2, with initial and repeat courses of moderately emetogenic cancer chemotherapy, with radiotherapy in patients receiving either total body irradiation, single high-dose fraction to the abdomen, or daily fractions to the abdomen, and prevention of postoperative nausea and/or vomiting. ORAL KYTRIL is indicated for the prevention of nausea and vomiting associated with initial and repeat courses of emetogenic cancer therapy, including high-dose cisplatin, and nausea and vomiting associated with radiation, including total body irradiation and fractionated abdominal radiation. ORAL ANZEMET is indicated for the prevention of nausea and vomiting associated with moderately emetogenic cancer chemotherapy, including initial and repeat courses and the prevention of postoperative nausea and vomiting. REFERENCES

Glaxo Smith Kline. Zofran® (ondansetron) package insert. Research Triangle Park, NC. September 2009.

Par Pharmaceutical. Zuplenz® (ondansetron) package insert. Woodcliff Lake, NJ. July 2010.

Roche Laboratories Inc. Kytril® (granisetron) package insert. Nutley, NJ. March 2010.

Sanofi Aventis U.S. LLC. Anzemet® (dolasetron) package insert. Kansas City, MO. October 2009.

Antiemesis version 2.2010. National Comprehensive Cancer Network Clinical Practice Guidelines in Oncology v 2.2010 [online]. Available at: http://www.nccn.org/professionals/physician_gls/PDF/antiemesis.pdf. [Accessed October 23, 2012].

American Society of Clinical Oncology Guideline for Antiemetics in Oncology: Update 2006 [online]. Available at: http://jco.ascopubs.org/cgi/content/short/24/18/2932. [Accessed October 23, 2012].

ACOG (American College Of Obstetrics And Gynecology): Practice Bulletin: Nausea And Vomiting Of Pregnancy. Obstet Gynecol 2004 Apr; 103(4): 803-14.

Medicare Prescription Drug Benefit Manual Chapter 6 – Part D Drugs and Formulary Requirements, Appendix C- Summary of Coverage Policy Medicare Part B Versus Part D Coverage Issues. Rev 10, 02-19-10. Available at: http://www.cms.gov/PrescriptionDrugCovContra/12_PartDManuals.asp. [Accessed October 23, 2012].


http://www.nccn.org/professionals/physician_gls/PDF/antiemesis.pdfhttp://www.cms.gov/PrescriptionDrugCovContra/12_PartDManuals.asp

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5HT3 ANTI-NAUSEA AGENT BVD DETERMINATION (PART D) For Part D use only:

5HT3 ANTI-NAUSEA AGENT BVD DETERMINATION

Covered uses THIS DRUG MAY BE COVERED UNDER MEDICARE PART B OR D DEPENDING UPON THE CIRCUMSTANCES. INFORMATION MAY NEED TO BE SUBMITTED DESCRIBING THE USE AND SETTING OF THE DRUG TO MAKE THE DETERMINATION.

Exclusion Criteria N/A

Required Medical Information N/A

Age Restrictions N/A

Prescriber Restrictions N/A

Coverage Duration N/A

Other Criteria N/A

Quantity Limit (from Formulary ASCII file)

N/A

Part D Effective: 01/01/14 Created: 09/05 Commercial Effective: N/A Client Approval: 11/13 P&T Approval: 11/13

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ABATACEPT - IV (PART D)


ABATACEPT/MALTOSE - IV ORENCIA - IV 33411

Do not review Part D guidelines with physicians; if the caller wishes to initiate an oral request then a verbal MRF must be completed. Please check the applicable CS note for processing. NOTE: For requests for the SQ dosage form of Orencia, please see the Orencia SQ PA Guideline. GUIDELINES FOR USE INITIAL CRITERIA (NOTE: FOR RENEWAL CRITERIA SEE BELOW) 1. Does the patient have a diagnosis of moderate to severe rheumatoid arthritis (RA) and meets all of

the following criteria:

therapy initiated by or in consultation with a rheumatologist

previous trial with at least one of the following DMARD (disease-modifying antirheumatic drug) agents such as methotrexate, leflunomide, hydroxychloroquine, or sulfasalazine

patient is 18 years of age or older

patient will not be on concurrent therapy with Kineret (anakinra), or a TNF (tumor necrosis factor) inhibitor: Humira, Enbrel, Cimzia, Remicade, Simponi, or Simponi Aria

previous trial with preferred formulary TNF (tumor necrosis factor) inhibitor Humira? If yes, approve for 4 months. APPROVAL TEXT: Renewal requires that the patient has experienced or maintained a 20% or greater improvement in tender joint count and swollen joint count while on therapy. If no, continue to #2.


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ABATACEPT - IV (PART D) INITIAL CRITERIA (CONTINUED) 2. Does the patient have a diagnosis of moderate to severe juvenile idiopathic arthritis (JIA) and meets

all of the following criteria:





previous trial with preferred formulary TNF (tumor necrosis factor) inhibitor Humira? If yes, approve for 4 months. APPROVAL TEXT: Renewal requires that the patient has experienced or maintained a 20% or greater improvement in tender joint count and swollen joint count while on therapy. If no, do not approve. INITIAL DENIAL TEXT: Our guideline for ABATACEPT - IV requires a diagnosis of moderate to severe rheumatoid arthritis (RA) or moderate to severe juvenile idiopathic arthritis (JIA). Additional guideline requirements apply. For moderate to severe rheumatoid arthritis, approval requires all of the following:





previous trial with preferred formulary TNF (tumor necrosis factor) inhibitor Humira For moderate to severe juvenile idiopathic arthritis, approval requires all of the following:





previous trial with preferred formulary TNF (tumor necrosis factor) inhibitor Humira


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ABATACEPT - IV (PART D) GUIDELINES FOR USE (CONTINUED) RENEWAL CRITERIA 1. Does the patient have a diagnosis of moderate to severe rheumatoid arthritis (RA) and meets the

following criteria:

documentation that the patient has experienced or maintained a 20% or greater improvement in tender and swollen joint count while on therapy? If yes, approve for 12 months. If no, continue to #2.

2. Does the patient have a diagnosis of moderate to severe juvenile idiopathic arthritis (JIA) and meets the following criteria?:

documentation that the patient has experienced or maintained a 20% or greater improvement in tender and swollen joint count while on therapy? If yes, approve for 12 months. If no, do not approve. RENEWAL DENIAL TEXT: Our guideline for ABATACEPT - IV renewal requires a diagnosis of moderate to severe rheumatoid arthritis (RA) or moderate to severe juvenile idiopathic arthritis (JIA). Additional guideline requirements apply. Renewal for moderate to severe rheumatoid arthritis requires:

documentation that the patient has experienced or maintained a 20% or greater improvement in tender and swollen joint count while on therapy.

Renewal for moderate to severe juvenile idiopathic arthritis requires:

documentation that the patient has experienced or maintained a 20% or greater improvement in tender and swollen joint count while on therapy.


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RATIONALE Ensure appropriate diagnostic, utilization and safety criteria are met for the management of requests for abatacept. FDA APPROVED INDICATIONS Monotherapy or concomitant use with DMARDs other than TNF antagonists in patients with moderate to severe active rheumatoid arthritis or concomitantly with MTX for moderately to severely active polyarticular juvenile idiopathic arthritis in pediatric patients 6 years of age and older. Adult Rheumatoid Arthritis (RA)

Moderately to severely active RA in adults. ORENCIA may be used as monotherapy or concomitantly with DMARDs other than TNF antagonists.

Polyarticular Juvenile Idiopathic Arthritis (PJIA)

Moderately to severely active polyarticular juvenile idiopathic arthritis in pediatric patients 6 years of age and older. ORENCIA may be used as monotherapy or concomitantly with MTX.

Important Limitations of Use

Should not be given concomitantly with TNF antagonists. REFERENCES

Bristol-Myers Squibb Corp. Orencia package insert. Princeton, NJ. December 2013.

Orencia. MedImpact P&T Monograph, November 2011.


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ABATACEPT - IV (PART D) For Part D use only:


Covered uses ALL FDA APPROVED INDICATIONS NOT OTHERWISE EXCLUDED FROM PART D.

Exclusion Criteria PATIENT WILL NOT BE ON CONCURRENT THERAPY WITH KINERET (ANAKINRA), OR A TNF (TUMOR NECROSIS FACTOR) INHIBITOR: HUMIRA, ENBREL, CIMZIA, REMICADE, SIMPONI, OR SIMPONI ARIA

Required Medical Information RENEWAL: RHEUMATOID ARTHRITIS/JUVENILE IDIOPATHIC ARTHRITIS/: EXPERIENCED OR MAINTAINED 20 PERCENT IMPROVEMENT IN TENDER AND SWOLLEN JOINT COUNT WHILE ON THERAPY.


Prescriber Restrictions PRESCRIBED BY OR IN CONSULTATION WITH: RHEUMATOID ARTHRITIS, JUVENILE IDIOPATHIC ARTHRITIS: RHEUMATOLOGIST

Coverage Duration INITIAL: 4 MONTHS RENEWAL: 12 MONTHS

Other Criteria INITIAL: FOR RHEUMATOID ARTHRITIS (RA) / JUVENILE IDIOPATHIC ARTHRITIS (JIA): PREVIOUS TRIAL WITH HUMIRA AND ONE DMARD (DISEASE-MODIFYING ANTIRHEUMATIC DRUG) AGENT SUCH AS METHOTREXATE, LEFLUNOMIDE, HYDROXYCHLOROQUINE, OR SULFASALAZINE. NOT APPROVED FOR PATIENTS ON CONCURRENT THERAPY WITH KINERET (ANAKINRA), OR A TNF (TUMOR NECROSIS FACTOR) INHIBITOR: HUMIRA, ENBREL, CIMZIA, REMICADE, SIMPONI, OR SIMPONI ARIA


NONE

Advantage Plus Plus N

Yes Yes No

Part D Effective: 01/01/16 Created 05/05 Commercial Effective: N/A Client Approval: 10/15 P&T Approval: 05/15

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ABATACEPT - SQ (PART D)


ABATACEPT - SQ ORENCIA - SQ 37825

Do not review Part D guidelines with physicians; if the caller wishes to initiate an oral request then a verbal MRF must be completed. Please check the applicable CS note for processing. NOTE: For requests for the IV dosage form of Orencia, please see the Orencia IV PA Guideline. GUIDELINES FOR USE INITIAL CRITERIA (NOTE: FOR RENEWAL CRITERIA SEE BELOW) 1. Does the patient have a diagnosis of moderate to severe rheumatoid arthritis (RA) and meets all of


Therapy initiated by or in consultation with a rheumatologist

Previous trial with at least one of the following DMARD (disease-modifying antirheumatic drug) agents: methotrexate, leflunomide, hydroxychloroquine, or sulfasalazine

Patient is 18 years of age or older

Patient will not be on concurrent therapy with Kineret (anakinra) or a TNF (tumor necrosis factor) inhibitor: Humira, Enbrel, Cimzia, Remicade, Simponi, or Simponi Aria

Previous trial with the preferred formulary TNF (tumor necrosis factor) inhibitor: Humira? If yes, approve for 4 months by GPID. APPROVAL TEXT: Renewal requires that the patient has experienced or maintained a 20% or greater improvement in tender joint count and swollen joint count while on therapy. If no, do not approve. DENIAL TEXT: Our guideline for ABATACEPT - SQ requires a diagnosis of moderate to severe rheumatoid arthritis (RA). Additional guideline requirements apply.

Therapy initiated by or in consultation with a rheumatologist

Previous trial with at least one of the following DMARD (disease-modifying antirheumatic drug) agents: methotrexate, leflunomide, hydroxychloroquine, or sulfasalazine

Patient is 18 years of age or older

Patient will not be on concurrent therapy with Kineret (anakinra) or a TNF (tumor necrosis factor) inhibitor: Humira, Enbrel, Cimzia, Remicade, Simponi, or Simponi Aria

Previous trial with the preferred formulary TNF (tumor necrosis factor) inhibitor: Humira


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ABATACEPT - SQ (PART D) GUIDELINES FOR USE (CONTINUED) RENEWAL CRITERIA 1. Does the patient have a diagnosis of moderate to severe rheumatoid arthritis (RA) and meets the

following criteria:

Documentation that the patient experienced or maintained a 20% or greater improvement in tender and swollen joint count while on therapy? If yes, approve for 12 months by GPID. If no, do not approve. DENIAL TEXT: Our guideline for ABATACEPT - SQ renewal requires a diagnosis of moderate to severe rheumatoid arthritis (RA). Additional guideline requirements apply.

Documentation that the patient experienced or maintained a 20% or greater improvement in tender and swollen joint count while on therapy

RATIONALE Ensure appropriate diagnostic, utilization and safety criteria are met for the management of requests for abatacept. Abatacept subcutaneous administration is only approved for the treatment of adult RA. Abatacept intravenous administration is approved for both treatment of adult RA and juvenile idiopathic arthritis. FDA APPROVED INDICATIONS Monotherapy or concomitant use with DMARDs other than TNF antagonists in patients with moderate to severe active rheumatoid arthritis or concomitantly with MTX for moderately to severely active polyarticular juvenile idiopathic arthritis in pediatric patients 6 years of age and older Adult Rheumatoid Arthritis (RA)

Moderately to severely active RA in adults. ORENCIA may be used as monotherapy or concomitantly with DMARDs other than TNF antagonists.

Polyarticular Juvenile Idiopathic Arthritis (PJIA)

Moderately to severely active polyarticular juvenile idiopathic arthritis in pediatric patients 6 years of age and older. ORENCIA may be used as monotherapy or concomitantly with MTX. The safety and efficacy of subcutaneous Orencia injection has not been studied in patients under 18 years of age.


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ABATACEPT - SQ (PART D) FDA APPROVED INDICATIONS (CONTINUED) Important Limitations of Use Should not be given concomitantly with TNF antagonists. Orencia is not recommended for use concomitantly with other biologic rheumatoid arthritis therapy such as anakinra. REFERENCES

Bristol-Myers Squibb Corp. Orencia package insert. Princeton, NJ. December 2013.

Orencia. MedImpact P&T Monograph, November 2011. For Part D use only:

ABATACEPT - SQ (PART D)



Required Medical Information RENEWAL: RHEUMATOID ARTHRITIS: EXPERIENCED OR MAINTAINED 20 PERCENT OR GREATER IMPROVEMENT IN TENDER AND SWOLLEN JOINT COUNT WHILE ON THERAPY.

Age Restrictions 18 YEARS OR OLDER.

Prescriber Restrictions RHEUMATOLOGIST.

Coverage Duration INITIAL: 4 MONTHS RENEWAL: 12 MONTHS

Other Criteria INITIAL: PREVIOUS TRIAL WITH HUMIRA AND ONE DMARD (DISEASE-MODIFYING ANTIRHEUMATIC DRUG) AGENTS SUCH AS METHOTREXATE, LEFLUNOMIDE, HYDROXYCHLOROQUINE, OR SULFASALAZINE. NOT APPROVED FOR PATIENTS ON CONCURRENT THERAPY WITH KINERET (ANAKINRA), OR A TNF (TUMOR NECROSIS FACTOR) INHIBITOR: HUMIRA, ENBREL, CIMZIA, REMICADE, SIMPONI, OR SIMPONI ARIA.


N/A


Yes Yes No


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ABIRATERONE (PART D)


ABIRATERONE ACETATE ZYTIGA 37571

Do not review Part D guidelines with physicians; if the caller wishes to initiate an oral request then a verbal MRF must be completed. Please check the applicable CS note for processing. GUIDELINES FOR USE 1. Does the patient have a diagnosis of metastatic castration-resistant prostate cancer?

If yes, continue to #2. If no, do not approve. DENIAL TEXT: See the denial text at the end of the guideline.

2. Will the patient be taking Zytiga in combination with prednisone?

If yes, approve for 12 months by HICL with a quantity limit of #4 tablets per day. If no, do not approve. DENIAL TEXT: See the denial text at the end of the guideline.

DENIAL TEXT: Our guideline for ABIRATERONE requires a diagnosis of metastatic castration-resistant prostate cancer and concurrent prednisone therapy.

RATIONALE To ensure appropriate use of Zytiga consistent with FDA approved indication. FDA APPROVED INDICATIONS Zytiga is indicated for use in combination with prednisone for the treatment of patients with metastatic castration-resistant prostate cancer. REFERENCES

Centocor Ortho Biotech Inc. package insert. Horsham, PA. December 2012.


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ABIRATERONE (PART D) For Part D use only:

ABIRATERONE (PART D)






Coverage Duration 12 MONTHS

Other Criteria N/A


120 IN 30


Yes Yes No


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ADALIMUMAB (PART D)


ADALIMUMAB HUMIRA 24800 ROUTE = SUBCUTANE. STRENGTHS = 10mg/0.2mL 20mg/0.4mL 40mg/0.8mL Psoriasis Starter Pack Crohn's-UC-HS Starter Pack

Do not review Part D guidelines with physicians; if the caller wishes to initiate an oral request then a verbal MRF must be completed. Please check the applicable CS note for processing. GUIDELINES FOR USE INITIAL CRITERIA (NOTE: FOR RENEWAL CRITERIA SEE BELOW) 1. Does the patient have a diagnosis of moderate to severe rheumatoid arthritis (RA) and meets all of


Therapy prescribed by or in consultation with a rheumatologist

Previous trial with at least one of the following DMARD (disease-modifying antirheumatic drug) agents such as methotrexate, leflunomide, hydroxychloroquine, or sulfasalazine

18 years of age or older

Patient will not be on concurrent therapy with Kineret (anakinra), Orencia (abatacept), Rituxan (rituximab), or a TNF (tumor necrosis factor) inhibitor (Enbrel, Cimzia, Remicade, Simponi, or Simponi Aria)? If yes, approve for 4 months by HICL. APPROVAL TEXT: Renewal requires that the patient has experienced or maintained a 20% or greater improvement in tender joint count or swollen joint count while on therapy. If no, continue to #2.


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ADALIMUMAB (PART D) INITIAL CRITERIA (CONTINUED) 2. Does the patient have a diagnosis of moderate to severe polyarticular juvenile idiopathic arthritis

(PJIA) and meets all of the following criteria:




Patient will not be on concurrent therapy with Kineret (anakinra), Orencia (abatacept), Rituxan (rituximab), or a TNF (tumor necrosis factor) inhibitor (Enbrel, Cimzia, Remicade, Simponi, or Simponi Aria)

Documentation of current weight? If yes, approve for 5 months by HICL. APPROVAL TEXT: Renewal requires that the patient has experienced or maintained a 20% or greater improvement in tender joint count or swollen joint count while on therapy. If no, continue to #3.

3. Does the patient have a diagnosis of psoriatic arthritis (PsA) and meets all of the following criteria:

Therapy prescribed by or in consultation with a rheumatologist or dermatologist



Patient will not be on concurrent therapy with Kineret (anakinra), Orencia (abatacept), Rituxan (rituximab), or a TNF (tumor necrosis factor) inhibitor (Enbrel, Cimzia, Remicade, Simponi, or Simponi Aria)? If yes, approve for 4 months by HICL. APPROVAL TEXT: Renewal requires that the patient has experienced or maintained a 20% or greater improvement in tender joint count or swollen joint count while on therapy. If no, continue to #4.


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ADALIMUMAB (PART D) INITIAL CRITERIA (CONTINUED) 4. Does the patient have a diagnosis of ankylosing spondylitis (AS) and meets all of the following

criteria:



Patient will not be on concurrent therapy with Kineret (anakinra), Orencia (abatacept), Rituxan (rituximab), or a TNF inhibitor (Enbrel, Cimzia, Remicade, Simponi, or Simponi Aria)? If yes, approve for 4 months by HICL. APPROVAL TEXT: Renewal requires that the patient has experienced or maintained an improvement of at least 50% or 2 units (scale of 1-10) in the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI). If no, continue to #5.

5. Does the patient have a diagnosis of moderate to severe plaque psoriasis (PsO) and meets all of the following criteria:

Therapy prescribed by or in consultation with a dermatologist

plaque psoriasis involving at least 5% body surface area (BSA) or psoriatic lesions affecting the hands, feet, or genital area

Previous trial with one of the following conventional therapies such as PUVA (Phototherapy Ultraviolet Light A), UVB (Ultraviolet Light B), topical corticosteroids, calcipotriene, acitretin, methotrexate, or cyclosporine


Patient will not be on concurrent therapy with Kineret (anakinra), Orencia (abatacept), Rituxan (rituximab), or a TNF inhibitor (Enbrel, Cimzia, Remicade, Simponi, or Simponi Aria)? If yes, approve for 3 months by HICL. APPROVAL TEXT: Renewal requires that the patient has achieved or maintained clear or minimal disease or a decrease in PASI (Psoriasis Area and Severity Index) of at least 50% or more. If no, continue to #6.


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ADALIMUMAB (PART D) INITIAL CRITERIA (CONTINUED) 6. Does the patient have a diagnosis of moderate to severe Crohn's disease (CD) and meets all of the

following criteria:

Therapy prescribed by or in consultation with a gastroenterologist

Previous trial with at least one of the following conventional agents such as corticosteroids (i.e., budesonide, methylprednisolone), azathioprine, mercaptopurine, methotrexate, or mesalamine


Patient will not be on concurrent therapy with Kineret (anakinra), Orencia (abatacept), Rituxan (rituximab), or a TNF inhibitor (Enbrel, Cimzia, Remicade, Simponi, or Simponi Aria)? If yes, approve for 3 months by HICL. If no, continue to #7.

7. Does the patient have a diagnosis of moderate to severe ulcerative colitis (UC) and meets all of the following criteria:


Previous trial with at least one of the following conventional agents such as corticosteroids (i.e., budesonide, methylprednisolone), azathioprine, mercaptopurine, methotrexate, or mesalamine


Patient will not be on concurrent therapy with Kineret (anakinra), Orencia (abatacept), Rituxan (rituximab), or a TNF inhibitor (Enbrel, Cimzia, Remicade, Simponi, or Simponi Aria)? If yes, approve for 3 months by HICL. If no, continue to #8.

8. Does the patient have a diagnosis of moderate to severe hidradenitis suppurativa (HS)? If yes, approve for 3 months by HICL. If no, do not approve. DENIAL TEXT: See the initial denial text at the end of the guideline.


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ADALIMUMAB (PART D) INITIAL DENIAL TEXT (CONTINUED)

INITIAL DENIAL TEXT: Our guideline for ADALIMUMAB requires a diagnosis of moderate to severe rheumatoid arthritis, psoriatic arthritis, moderate to severe polyarticular juvenile idiopathic arthritis, ankylosing spondylitis, moderate to severe plaque psoriasis, moderate to severe Crohn’s disease, moderate to severe ulcerative colitis, or hidradenitis suppurativa. Additional guideline requirements apply. For patients with moderate to severe rheumatoid arthritis (RA), approval requires all of the following:



Patient age of at least 18 years

Patient will not be on concurrent therapy with Kineret (anakinra), Orencia (abatacept), Rituxan (rituximab), or a TNF (tumor necrosis factor) inhibitor (Enbrel, Cimzia, Remicade, Simponi, or Simponi Aria)

For patients with moderate to severe polyarticular juvenile idiopathic arthritis (PJIA), approval requires all of the following:




Patient will not be on concurrent therapy with Kineret (anakinra), Orencia (abatacept), Rituxan (rituximab), or a TNF inhibitor (Enbrel, Cimzia, Remicade, Simponi, or Simponi Aria)

Documentation of patient's current weight For patients with psoriatic arthritis (PsA), approval requires all of the following:

Therapy prescribed by or in consultation with a rheumatologist or dermatologist




For patients with ankylosing spondylitis (AS), approval requires all of the following:




(INITIAL DENIAL TEXT CONTINUED ON NEXT PAGE)


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ADALIMUMAB (PART D) INITIAL DENIAL TEXT (CONTINUED)

For patients with moderate to severe plaque psoriasis (PsO), approval requires all of the following:

Therapy prescribed by or in consultation with a dermatologist

plaque psoriasis involving at least 5% body surface area (BSA) or psoriatic lesions affecting the hands, feet, or genital area

Previous trial with one of the following conventional therapies such as PUVA (Phototherapy Ultraviolet Light A), UVB (Ultraviolet Light B), topical corticosteroids, calcipotriene, acitretin, methotrexate, or cyclosporine



For patients with moderate to severe Crohn’s disease, approval requires all of the following:


Previous trial with one or more of the following conventional agents such as corticosteroids (i.e., budesonide, methylprednisolone), azathioprine, mercaptopurine, methotrexate, or mesalamine



For patients with moderate to severe ulcerative colitis (UC), approval requires all of the following:


Previous trial with one or more of the following conventional agents such as corticosteroids (i.e., budesonide, methylprednisolone), azathioprine, mercaptopurine, methotrexate, or mesalamine



RENEWAL CRITERIA 1. Does the patient have a diagnosis of moderate to severe rheumatoid arthritis (RA) and meets the

following criteria:

Documentation that the patient has experienced or maintained a 20% or greater improvement in tender or swollen joint count while on therapy? If yes, approve for 12 months. If no, continue to #2.


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ADALIMUMAB (PART D) RENEWAL CRITERIA (CONTINUED) 2. Does the patient have a diagnosis of moderate to severe polyarticular juvenile idiopathic arthritis

(PJIA) and meets the following criteria:


3. Does the patient have a diagnosis of psoriatic arthritis (PsA) and meets the following criteria:


4. Does the patient have a diagnosis of ankylosing spondylitis (AS) and meets the following criteria:

Documentation that the patient has experienced or maintained an improvement of at least 50% or 2 units (scale of 1-10) in the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI)? If yes, approve for 12 months. If no, continue to #5.

5. Does the patient have a diagnosis of moderate to severe plaque psoriasis (PsO) and meets the following criteria:

Documentation that the patient has achieved or maintained clear or minimal disease or a decrease in PASI (Psoriasis Area and Severity Index) of at least 50% or more? If yes, approve for 12 months. If no, continue to #6.

6. Does the patient have a diagnosis of moderate to severe Crohn's disease (CD), moderate to severe ulcerative colitis (UC), or moderate to severe hidradenitis suppurativa (HS)?

If yes, approve for 12 months. If no, do not approve. DENIAL TEXT: See the renewal denial text at the end of the guideline.


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ADALIMUMAB (PART D) RENEWAL CRITERIA (CONTINUED)

RENEWAL DENIAL TEXT: Our guideline for ADALIMUMAB renewal requires a diagnosis of moderate to severe rheumatoid arthritis, psoriatic arthritis, moderate to severe juvenile idiopathic arthritis, ankylosing spondylitis, moderate to severe chronic plaque psoriasis, moderate to severe Crohn's disease, moderate to severe ulcerative colitis, or moderate to severe hidradenitis suppurativa. Additional guideline requirements apply. Renewal for the diagnosis of moderate to severe rheumatoid arthritis (RA) requires:

Documentation that the patient has experienced or maintained a 20% or greater improvement in tender or swollen joint count while on therapy

Renewal for the diagnosis of moderate to severe polyarticular juvenile idiopathic arthritis (PJIA) requires:


Renewal for the diagnosis of psoriatic arthritis (PsA) requires:


Renewal for the diagnosis of ankylosing spondylitis (AS) requires:

Documentation that the patient has experienced or maintained an improvement of at least 50% or 2 units (scale of 1-10) in the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI)

Renewal for the diagnosis of moderate to severe plaque psoriasis (PsO) requires:

Documentation that the patient has achieved or maintained clear or minimal disease or a decrease in PASI (Psoriasis Area and Severity Index) of at least 50% or more

RATIONALE Ensure appropriate diagnostic, utilization and safety criteria are used for the management of requests for adalimumab. FDA APPROVED INDICATIONS HUMIRA is indicated for reducing signs and symptoms, inducing major clinical response, inhibiting the progression of structural damage and improving physical function in adult patients with moderately to severely active rheumatoid arthritis. HUMIRA can be used alone or in combination with methotrexate or other non-biologic disease-modifying anti-rheumatic drugs (DMARDs). HUMIRA is indicated for reducing signs and symptoms, inhibiting the progression of structural damage, and improving physical function in adult patients with active psoriatic arthritis. HUMIRA can be used alone or in combination with non-biologic (DMARDs). HUMIRA is indicated for reducing signs and symptoms in patients with active ankylosing spondylitis.


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ADALIMUMAB (PART D) FDA APPROVED INDICATIONS (CONTINUED) HUMIRA is indicated for reducing signs and symptoms, inducing, and maintaining clinical remission in adults with moderately to severely active Crohn's disease who have had an inadequate response to conventional therapy. HUMIRA is indicated for reducing signs and symptoms and inducing clinical remission in these patients if they have also lost response to or are intolerant to infliximab. HUMIRA is indicated for reducing signs and symptoms and inducing and maintaining clinical remission in pediatric patients 6 years of age and older with moderately to severely active Crohn’s disease who have had an inadequate response to corticosteroids or immunomodulators such as azathioprine, 6-mercaptopurine, or methotrexate. HUMIRA is indicated for inducing and sustaining clinical remission in adult patients with moderately to severely active ulcerative colitis who have had an inadequate response to immunosuppressant's such as corticosteroids, azathioprine, or 6-mercaptopurine (6-MP). The effectiveness of HUMIRA has not been established in patients who have lost response to or were intolerant to TNF blockers. HUMIRA is indicated for the treatment of adult patients with moderate to severe chronic plaque psoriasis who are candidates for systemic therapy or phototherapy, and when other systemic therapies are medically less appropriate. HUMIRA should only be administered to patients who will be closely monitored and have regular follow-up visits with a physician. HUMIRA is indicated for the treatment of moderate to severe hidradenitis suppurativa. Dosing: Rheumatoid Arthritis, Psoriatic Arthritis, Ankylosing Spondylitis 40mg every other week. Some patients with RA not receiving methotrexate may benefit from increasing the frequency to 40 mg every week. Juvenile Idiopathic Arthritis The recommended dose of HUMIRA for patients 2 years of age and older with polyarticular juvenile idiopathic arthritis (JIA) is based on weight as shown below: 10kg (22lbs) to

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ADALIMUMAB (PART D) DOSING (CONTINUED) Plaque Psoriasis 80 mg initial dose followed by 40 mg every other week starting one week after initial dose. Adult Hidradenitis Suppurativa Initial dose (Day 1) is 160mg (four 40mg injections I one day or two 40mg injections per day for two consecutive days), followed by 80mg two weeks later (Day 15). Two weeks later (Day 29) begin a maintenance dose of 40mg every week. Pediatric Crohn's Disease

17 kg to

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ADALIMUMAB (PART D) REFERENCES

Abbott Laboratories. Humira product information. North Chicago, IL. September, 2015.

Bristol-Myers Squibb. Orencia product information. Princeton, NJ. November, 2009.

Felson D, Anderson J, Boers M, et al. American College of Rheumatology preliminary definition of improvement in rheumatoid arthritis. Arthritis Rheum 1995; 38:727-35.

Mease P, Gladman D, Ritchlin C, et al. Adalimumab for the treatment of patients with moderately to severely active psoriatic arthritis. Arthritis and Rheumatism 2005; 52:3279-89.

Braun J, Davis J et al. First update of the international ASAS consensus statement for the use of anti-TNF agents in patients with ankylosing spondylitis. Ann Rheum Dis. 2006; 65(3):316-20.

Hanauer SB, Sandborn WJ, Rutgeerts P, et al. Human Anti-Tumor Necrosis Factor Monoclonal Antibody (Adalimumab) in Crohn's Disease: the CLASSIC-I Trial. Gastroenterology. 2006; 130: 323-333.

Colombel JF, Sandborn WJ, Rutgeerts P, et al. Adalimumab for Maintenance of Clinical Response and Remission in Patients With Crohn's Disease: The CHARM Trial. Gastroenterology. 2007; 132: 53-65.

Papadakis KA, Shaye OA, Vasiliauskas EA, et al. Safety and Efficacy of Adalimumab (D2E7) in Crohn's Disease Patients with an Attenuated Response to Infliximab. Am J Gastro. 2005; 75-79.

Clinical Pharmacology [database online]. Tampa, FL: Gold Standard, Inc.; 2009. Available at: http://www.clinicalpharmacology.com. [Accessed: June 22, 2010].

For Part D use only:

ADALIMUMAB (PART D)

Covered uses ALL FDA APPROVED INDICATIONS NOT OTHERWISE

EXCLUDED FROM PART D.

Exclusion Criteria NA

Required Medical Information INITIAL: POLYARTICULAR JUVENILE IDIOPATHIC ARTHRITIS:

CURRENT WEIGHT; PLAQUE PSORIASIS: MODERATE TO

SEVERE PLAQUE PSORIASIS INVOLVING GREATER THAN

OR EQUAL TO 5 PERCENT BODY SURFACE AREA OR

PSORIATIC LESIONS AFFECT THE HANDS, FEET, OR

GENITAL AREA. RENEWAL: RHEUMATOID

ARTHRITIS/JUVENILE IDOPATHIC ARTHRITIS/PSORIATIC

ARTHRITIS: EXPERIENCED OR MAINTAINED 20 PERCENT

IMPROVEMENT IN TENDER OR SWOLLEN JOINT COUNT

WHILE ON THERAPY. ANKYLOSING SPONDYLITIS:

EXPERIENCED OR MAINTAINED IMPROVEMENT OF AT

LEAST 50 PERCENT OR 2 UNITS IN THE BATH ANKYLOSING

SPONDYLITIS DISEASE ACTIVITY INDEX (BASDAI). PLAQUE

PSORIASIS: ACHIEVED OR MAINTAINED CLEAR OR MINIMAL

DISEASE OR A DECREASE IN PSORIASIS AREA AND

http://www.clinicalpharmacology.com/

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SEVERITY INDEX (PASI) OF AT LEAST 50% OR MORE.

Age Restrictions NA

Prescriber Restrictions PRESCRIBED BY OR IN CONSULTATION WITH: RHEUMATOID

ARTHRITIS, POLYARTICULAR JUVENILE IDIOPATHIC

ARTHRITIS, ANKYLOSING SPONDYLITIS:

RHEUMATOLOGIST; PSORIATIC ARTHRITIS:

DERMATOLOGIST OR RHEUMATOLOGIST; PSORIASIS:

DERMATOLOGIST; CROHN’S DISEASE/ULCERATIVE COLITIS:

GASTROENTEROLOGIST.

Coverage Duration INITIAL: RA /PSA/AS: 4 MONTHS; PJIA: 5

MONTHS;PSO/CD/UC/HS: 3 MONTHS RENEWAL: 12 MONTHS

FOR ALL DIAGNOSES

Other Criteria INITIAL: RHEUMATOID ARTHRITIS (RA)/POLYARTICULAR

JUVENILE IDIOPATHIC ARTHRITIS (PJIA)/PSORIATRIC

ARTHRITIS (PSA): PREVIOUS TRIAL WITH ONE DMARD

(DISEASE-MODIFYING ANTIRHEUMATIC DRUG) AGENT

SUCH AS METHOTREXATE, LEFLUNOMIDE,

HYDROXYCHLOROQUINE, OR SULFASALAZINE; PLAQUE

PSORIASIS (PSO): PREVIOUS TRIAL WITH ONE OF THE

FOLLOWING CONVENTIONAL THERAPIES SUCH AS PUVA

(PHOTOTHERAPY ULTRAVIOLET LIGHT A), UVB

(ULTRAVIOLET LIGHT B), TOPICAL CORTICOSTEROIDS,

CALCIPOTRIENE, ACITRETIN, METHOTREXATE, OR

CYCLOSPORINE; CROHN’S DISEASE (CD)/ULCERATIVE

COLITIS (UC): PREVIOUS TRIAL WITH ONE OF THE

FOLLOWING CONVENTIONAL AGENTS SUCH AS

CORTICOSTEROIDS (I.E., BUDESONIDE,

METHYLPREDNISOLONE), AZATHIOPRINE,

MERCAPTOPURINE, METHOTREXATE, OR MESALAMINE);

NOT APPROVED FOR PATIENT ON CONCURRENT THERAPY

WITH KINERET (ANAKINRA), ORENCIA (ABATACEPT),

RITUXAN (RITUXIMAB), OR A TNF INHIBITOR (ENBREL,

CIMZIA, REMICADE, SIMPONI, OR SIMPONI ARIA)

Quantity Limit (from Formulary

ASCII file)

NONE


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ADALIMUMAB (PART D)


Yes Yes No


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ADO-TRASTUZUMAB EMTANSINE (PART D)


ADO-TRASTUZUMAB EMTANSINE KADCYLA 40046

Do not review Part D guidelines with physicians; if the caller wishes to initiate an oral request then a verbal MRF must be completed. Please check the applicable CS note for processing. GUIDELINES FOR USE 1. Does the patient have a diagnosis of metastatic breast cancer?

If yes, continue to #2. If no, do not approve. DENIAL TEXT: See the denial text at the end of the guideline..

2. Is the patient's breast cancer HER2 positive (defined as IHC 3+ or FISH amplification ratio greater than 2.0)?


3. Has the patient received prior therapy for metastatic disease (such as Perjeta with Herceptin and a taxane (either docetaxel or paclitaxel); or Herceptin with paclitaxel (with or without carboplatin), docetaxel, vinorelbine, or Xeloda); or developed disease recurrence during or within six months of completing adjuvant therapy?

If yes, approve for 12 months. If no, do not approve. DENIAL TEXT: See the denial text at the end of the guideline.

DENIAL TEXT: Our guideline for ADO-TRASTUZUMAB EMTANSINE requires a diagnosis of metastatic breast cancer that is HER2 positive and prior therapy for metastatic disease or patient has developed disease recurrence during or within six months of completing adjuvant therapy.

RATIONALE To ensure appropriate use aligned with FDA approved indications and NCCN guidelines.


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ADO-TRASTUZUMAB EMTANSINE (PART D) RATIONALE (CONTINUED) The recommended dose of Kadcyla is 3.6 mg/kg given as an intravenous infusion every 3 weeks (21-day cycle) until disease progression or unacceptable toxicity. Do not administer Kadcyla at doses greater than 3.6 mg/kg. Do not substitute Kadcyla for or with Herceptin. Administer infusion over 90 minutes for first dose. Patients should be observed during the infusion and for at least 90 minutes following the initial dose for fever, chills, or other infusion related reactions. Subsequent infusions can be administered over 30 minutes if prior infusions were well tolerated. Patients should be observed during the infusion and for at least 30 minutes after infusion. If a planned dose is delayed or missed, it should be administered as soon as possible; do not wait until the next planned cycle. The schedule of administration should be adjusted to maintain a 3-week interval between doses. The infusion may be administered at the dose and rate the patient tolerated in the most recent infusion. The infusion rate of Kadcyla should be slowed or interrupted if the patient develops an infusion-related reaction. Permanently discontinue Kadcyla for life-threatening infusion related reactions. Management of increased serum transaminases, hyperbilirubinemia, left ventricular dysfunction, thrombocytopenia, pulmonary toxicity or peripheral neuropathy may require temporary interruption, dose reduction, or treatment discontinuation of Kadcyla. The first dose reduction is to 3mg/kg, followed by a reduction to 2.4mg/kg. Any further reduction should result in discontinuation of treatment. A reduction in the dose is recommended in the case of hepatotoxicity signaled by increases in serum transaminases and/or hyperbilirubinemia or in the case of Grade 4 thrombocytopenia (platelets < 25,000/mm3). Temporary discontinuation is recommended for patients experiencing Grade 3 or 4 peripheral neuropathy until resolution to ≤ Grade 2. Permanent discontinuation is advised for patients with serum transaminases > 3 x ULN and concomitant total bilirubin > 2 x ULN; patients diagnosed with nodular regenerative hyperplasia (NRH), interstitial lung disease (ILD), or pneumonitis. Kadcyla (ado-trastuzumab emtansine) is a HER2-targeted antibody-drug conjugate of Herceptin (trastuzumab) and DM1, a microtubule inhibitor. DM1 is too toxic to deliver directly into a patient's bloodstream, like other chemotherapy drugs. The Herceptin component of Kadcyla targets and delivers DM1 directly into cancer cells, sparing noncancerous cells. Upon binding to sub-domain IV of the HER2 receptor, ado-trastuzumab emtansine undergoes receptor-mediated internalization and subsequent lysosomal degradation, resulting in intracellular release of DM1-containing cytotoxic catabolites. Binding of DM1 to tubulin disrupts microtubule networks in the cell, which results in cell cycle arrest and apoptotic cell death.


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ADO-TRASTUZUMAB EMTANSINE (PART D) RATIONALE (CONTINUED) Breast cancer is the most common cancer among women and the second leading cause of cancer death. An estimated 232,340 Americans will be diagnosed with breast cancer and another 39,620 will die of it in 2013. The most common risk factors are female gender and increasing age. The five year survival rate for metastatic breast cancer is 15%. In HER2-positive breast cancers, the increased amount of the protein contributes to cancer call growth and survival. Nearly 20% of breast cancers have increased amounts of HER2.

The National Comprehensive Cancer Network (NCCN) guidelines recommend Perjeta (pertuzumab) with Herceptin and a taxane (either docetaxel or paclitaxel) as the preferred first-line therapy for HER2 positive metastatic breast cancer. Other first-line regimens include Herceptin with: paclitaxel ± carboplatin, docetaxel, vinorelbine, or Xeloda (capecitabine). Regimens for Herceptin-exposed HER2-positive disease include:

Tykerb + Xeloda

Herceptin + Xeloda

Herceptin + Tykerb (without cytotoxic therapy)

Herceptin + other agents Additional phase III studies may expand upon Kadcyla’s initial indication. Kadcyla alone or in combination with Perjeta is being evaluated against Herceptin plus taxane (docetaxel or paclitaxel) in patients with HER2-positive progressive or recurrent locally advanced or previously untreated metastatic breast cancer in the MARIANNE study, with initial results expected in the first half 2014. The TH3RESA study will evaluate Kadcyla with treatment of the physician's choice in patients with metastatic or unresectable locally advanced/recurrent HER2-positive breast cancer previously treated with Herceptin, a taxane, and Tykerb and disease progression after at least two regimens of HER2-directed therapy. Additionally Kadcyla is being studied as adjuvant therapy for HER2-positive breast cancer in the KATHERINE study and for advanced gastric cancer in another trial. Kadcyla’s pivotal trial included in the prescribing information was the EMILIA study; a randomized, multicenter, open-label Phase III trial of 991 patients with HER2-positive, unresectable locally advanced or metastatic breast cancer. Prior taxane and trastuzumab-based therapy was required before trial enrollment. Patients with only prior adjuvant therapy were required to have disease recurrence during or within six months of completing adjuvant therapy. Breast tumor samples were required to show HER2 over expression defined as 3+ IHC or FISH amplification ratio ≥ 2.0 determined at a central laboratory. Patients were randomly allocated (1:1) to receive Tykerb plus Xeloda or Kadcyla. Randomization was stratified by world region (United States, Western Europe other), number of prior chemotherapy regimens for unresectable locally advanced or metastatic disease (0–1, >1) and visceral versus non-visceral disease as determined by the investigators.


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ADO-TRASTUZUMAB EMTANSINE (PART D) RATIONALE (CONTINUED) Kadcyla was given intravenously at 3.6 mg/kg on Day 1 of a 21-day cycle. Tykerb was administered at 1250 mg/day orally once per day of a 21-day cycle and Xeloda was administered at 1000 mg/m2 orally twice daily on Days 1−14 of a 21-day cycle. Patients were treated with Kadcyla or Tykerb plus Xeloda until progression of disease, withdrawal of consent, or unacceptable toxicity. At the time of the primary analysis, median time on study drug was 5.7 months for Kadcyla, 4.9 months for Tykerb, and 4.8 months for Xeloda. The co-primary efficacy endpoints of the study were progression-free survival (PFS) based on tumor response assessments by an independent review committee (IRC), and overall survival (OS). Additional endpoints included PFS (based on investigator tumor response assessments), objective response rate (ORR), duration of response and time to symptom progression. Patient demographics and baseline tumor characteristics were balanced between treatment arms. The median age was approximately 53 years (range 24-84 years and all but 5 patients were women. Tumor prognostic characteristics including hormone receptor status (positive: 55%, negative: 43%), presence of visceral disease (68%) and non-visceral disease only (33%) and the number of metastatic sites (< 3: 61%, ≥ 3: 37%) were similar in the study arms. The majority of patients (88%) had received prior systemic treatment in the metastatic setting. All but one patient received Herceptin prior to study entry; approximately 85% of patients received prior Herceptin in the metastatic setting. Over 99% percent of patients had received a taxane, and 61% of patients had received an anthracycline prior to study entry. Overall, patients received a median of 3 systemic agents in the metastatic setting. Among patients with hormone receptor-positive tumors, 44.4% received prior adjuvant hormonal therapy and 44.8% received hormonal therapy for locally advanced/metastatic disease. Median progression-free survival as assessed by independent review was 9.6 months with Kadcyla versus 6.4 months with Tykerb plus Xeloda (hazard ratio for progression or death from any cause, 0.65; 95% confidence interval [CI], 0.55 to 0.77; P

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ADO-TRASTUZUMAB EMTANSINE (PART D) RATIONALE (CONTINUED) A treatment benefit with Kadcyla in terms of PFS and OS was observed in patient subgroups based on stratification factors, key baseline demographic and disease characteristics, and prior treatments. In the subgroup of patients with hormone receptor-negative disease (n=426), the hazard ratios for PFS and OS were 0.56 (95% CI: 0.44, 0.72) and 0.75 (95% CI: 0.54, 1.03), respectively. In the subgroup of patients with hormone receptor-positive disease (n=545), the hazard ratios for PFS and OS were 0.72 (95% CI: 0.58, 0.91) and 0.62 (95% CI: 0.46, 0.85), respectively. In the subgroup of patients with non-measurable disease (n=205), based on IRC assessments, the hazard ratios for PFS and OS were 0.91 (95% CI: 0.59, 1.42) and 0.96 (95% CI: 0.54, 1.68), respectively; in patients with measurable disease the hazard ratios were 0.62 (95% CI: 0.52, 0.75) and 0.65 (95% CI: 0.51, 0.82), respectively. The PFS and OS hazard ratios in patients who were younger than 65 years old (n=853) were 0.62 (95% CI: 0.52, 0.74) and 0.66 (95% CI: 0.52, 0.83), respectively. In patients ≥ 65 years old (n=138), the hazard ratios for PFS and OS were 1.06 (95% CI: 0.68, 1.66) and 1.05 (95% CI: 0.58, 1.91), respectively. Kadcyla has boxed warnings for hepatotoxicity, cardiac toxicity, and embryo-fetal toxicity. Warnings and precautions include pulmonary toxicity, infusion-related reactions, hypersensitivity reactions, thrombocytopenia, and neurotoxicity. The most common adverse drug reactions (frequency > 25%) with Kadcyla were fatigue, nausea, musculoskeletal pain, thrombocytopenia, headache, increased transaminases, and constipation. Nursing mothers should discontinue nursing or discontinue Kadcyla taking into consideration the importance of the drug to the mother. Females of reproductive potential should be counseled on pregnancy prevention and planning. These patients are encouraged to participate in the MotHER Pregnancy Registry. Kadcyla is pregnancy category D. NCCN considers either immunohistochemistry (IHC) or in situ hybridization (ISH) tests as an acceptable method for making an initial determination of HER2 tumor status. Breast cancer tumors are classified as HER2 positive if they are scored as 3+ by an IHC method. FDA APPROVED INDICATIONS Kadcyla (ado-trastuzumab emtansine) is indicated, as a single agent, for the treatment of patients with HER2-positive, metastatic breast cancer who previously received trastuzumab and a taxane, separately or in combination. Patients should have either:

Received prior therapy for metastatic disease, or

Developed disease recurrence during or within six months of completing adjuvant therapy.


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REFERENCES

Kadcyla [Prescribing Information]. South San Francisco, CA: Genentech, Inc.; February 2013.

Verma S, Miles D, Gianni L, et al. Trastuzumab Emtansine for HER2-Positive Advanced Breast Cancer. N Engl J Med 2012; 367:1783-91.

National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology : Breast Cancer. Version 1.2013. Available at: http://www.nccn.org/professionals/physician_gls/pdf/breast.pdf [Accessed March 4, 2013].

American Cancer Society. Breast Cancer Detailed Guide. Available at: http://www.cancer.org/cancer/breastcancer [Accessed March 4, 2013].

A Study of Trastuzumab Emtansine (T-DM1) Plus Pertuzumab/Pertuzumab Placebo Versus Trastuzumab [Herceptin] Plus a Taxane in Patients With Metastatic Breast Cancer (MARIANNE). Available at: http://clinicaltrials.gov/show/NCT01120184 [Accessed March 4, 2013].

A Study of Trastuzumab Emtansine in Comparison With Treatment of Physician's Choice in Patients With HER2-Positive Breast Cancer Who Have Received at Least Two Prior Regimens of HER2-Directed Therapy (TH3RESA). Available at: http://clinicaltrials.gov/show/NCT01419197 [Accessed March 4, 2013].

A Study of Trastuzumab Emtansine Versus Trastuzumab as Adjuvant Therapy in Patients With HER2-Positive Breast Cancer Who Have Residual Tumor in the Breast or Axillary Lymph Nodes Following Preoperative Therapy (KATHERINE). Available at: http://clinicaltrials.gov/ct2/show/NCT01772472 [Accessed March 4, 2013].

A Study of Trastuzumab Emtansine Versus Taxane in Patients With Advanced Gastric Cancer. Available at: http://clinicaltrials.gov/ct2/show/NCT01641939 [Accessed March 4, 2013].

For Part D use only:







Coverage Duration 12 MONTHS

Other Criteria N/A


NONE


Yes Yes No


http://www.nccn.org/professionals/physician_gls/pdf/breast.pdfhttp://www.cancer.org/cancer/breastcancerhttp://clinicaltrials.gov/show/NCT01120184http://clinicaltrials.gov/show/NCT01419197http://clinicaltrials.gov/ct2/show/NCT01772472http://clinicaltrials.gov/ct2/show/NCT01641939?term=trastuzumab+emtansine&rank=1

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AFATINIB (PART D)


AFATINIB DIMALEATE GILOTRIF 40478

Do not review Part D guidelines with physicians; if the caller wishes to initiate an oral request then a verbal MRF must be completed. Please check the applicable CS note for processing. GUIDELINES FOR USE 1. Does the patient have a diagnosis of metastatic, non-small cell lung cancer (NSCLC)?


2. Do the patients' tumors have epidermal growth factor receptor (EGFR) exon 19 deletions or exon 21 (L858R) substitution mutations as detected by an FDA-approved test?

If yes, approve for 12 months by HICL with a quantity limit of #30 tablets in 30 days. If no, do not approve. DENIAL TEXT: See the denial text at the end of the guideline.

DENIAL TEXT: Our guideline for AFATINIB requires a diagnosis of metastatic, non-small cell lung cancer (NSCLC) and, tumors have epidermal growth factor receptor (EGFR) exon 19 deletions or exon 21 (L858R) substitution mutations as detected by an FDA-approved test.

RATIONALE Based on FDA approved indication and NCCN recommendations. Gilotrif is indicated for the treatment of NSCLC as first line therapy in patients whose tumor expresses EGFR exon 19 deletions or exon 21 (L858R) substitutions. NCCN recommends its use as first or second line treatment of NSCLC with EGFR exon 19 deletions or exon 21 (L858R) substitutions. The recommended dose of Gilotrif is 40 mg orally once daily until disease progression or no longer tolerated by the patient. Take Gilotrif at least 1 hour before or 2 hours after a meal. Do not take a missed dose within 12 hours of the next dose. Withhold Gilotrif for any drug-related adverse reactions of:

National Cancer Institute Common Terminology Criteria for Adverse Events Grade 3 or higher

Diarrhea of Grade 2 or higher persisting for 2 or more consecutive days while taking anti-diarrheal medication

Cutaneous reactions of Grade 2 that are prolonged (lasting more than 7 days) or intolerable

Renal dysfunction of Grade 2 or higher


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AFATINIB (PART D) RATIONALE (CONTINUED) Resume treatment when the adverse reaction fully resolves, returns to baseline, or improves to Grade 1 Reinstitute Gilotrif at a reduced dose, i.e., 10 mg per day less than the dose at which the adverse reaction occurred. Permanently discontinue Gilotrif for:

Life-threatening bullous, blistering, or exfoliative skin lesions

Confirmed interstitial lung disease (ILD)

Severe drug-induced hepatic impairment

Persistent ulcerative keratitis

Symptomatic left ventricular dysfunction

Severe or intolerable adverse reaction occurring at a dose of 20 mg per day Gilotrif has warnings for diarrhea, bullous and exfoliative skin disorders, interstitial lung disease (ILD), hepatic toxicity, keratitis, and embryofetal toxicity. Gilotrif is pregnancy category D. Nursing mothers should discontinue Gilotrif or nursing. The most common adverse reactions (≥20%) are diarrhea, rash/dermatitis acneiform, stomatitis, paronychia, dry skin, decreased appetite, and pruritus. Co-administration of P-gp inhibitors can increase afatinib exposure. Reduce Gilotrif by 10 mg per day if not tolerated. Co-administration of chronic Pgp inducers orally can decrease afatinib exposure. Increase Gilotrif by 10 mg per day as tolerated. Gilotrif versus Alimta with Cisplatin: EGFR Mutation Positive 1st line NSCLC (11) (12) (13) LUX-Lung 3 (Study 1 in prescribing information) was a randomized, multicenter, open-label trial that evaluated Gilotrif in the first-line treatment of 345 patients with EGFR mutation-positive, metastatic (Stage IV and Stage IIIb with pleural and/or pericardial effusion) NSCLC. Patients were randomized (2:1) to receive Gilotrif 40 mg orally once daily (n=230) or up to 6 cycles of Alimta/cisplatin (n=115). Randomization was stratified according to EGFR mutation status (exon 19 deletion versus exon 21 L858R versus other) and race (Asian versus non-Asian). The major efficacy outcome was progression-free survival (PFS) as assessed by an independent review committee (IRC). Other efficacy outcomes included objective response rate (ORR) and overall survival (OS). EGFR mutation status was prospectively determined for screening and enrollment of patients by a clinical trial assay (CTA). Tumor samples from 264 patients (178 randomized to Gilotrif and 86 patients randomized to chemotherapy) were tested retrospectively by the companion diagnostic therascreen® EGFR RGQ PCR Kit, which is FDA-approved for selection of patients for Gilotrif treatment.


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AFATINIB (PART D) RATIONALE (CONTINUED) Among the patients randomized, 65% were female, the median age was 61 years, the baseline ECOG performance status was 0 (39%) or 1 (61%), 26% were Caucasian and 72% were Asian. The majority of the patients had a tumor sample with an EGFR mutation categorized by the CTA as either exon 19 deletion (49%) or exon 21 L858R substitution (40%), while the remaining 11% had other mutations. A statistically significant improvement in PFS as determined by the IRC was demonstrated for patients randomized to Gilotrif compared with those randomized to chemotherapy; 11.1 versus 6.9 months. There was no statistically significant difference for overall survival between the treatment arms at the interim analysis conducted at 84% of the planned events for the final analysis. Median survival was longer than anticipated with platinum-doublet chemotherapy so cross-over to the Gilotrif arm may have obscured Gilotrif’s overall survival benefit. Efficacy Results of Study 1 (From Gilotrif prescribing information)

GILOTRIF (N=230)

Premetrexed/Cisplatin (N-115)

Progression-free Survival

Number of Deaths or Progressions, N (%) 152 (66.1%) 69 (60.0%)

Median Progression-free Survival (months) 11.1 6.9

95% CI (9.6,13.6) (5.4,8.2)

Documents

Plus Medicare Part D Formulary Prior Authorization …...cancer chemotherapeutic regimen within 48 hours of the patient receiving cancer treatment is billed under Part B. The assumption