Keytruda (pembrolizumab) Line(s) of Business: HMO; PPO; QUEST Integration Akamai Advantage Original Effective Date: 10/01/2015 Current Effective Date: 07/24/2017TBD03/01/2018 POLICY A. INDICATIONS The indications below including FDA-approved indications and compendial uses are considered covered benefit provided that all the approval criteria are met and the member has no exclusions to the prescribed therapy. FDA-Approved Indications Classic Hodgkin Lymphoma Keytruda is indicated for the treatment of adult and pediatric patients with refractory classical Hodgkin Lymphoma (chl), or who have relapsed after 3 or more prior lines of therapy. Melanoma Keytruda is indicated for the treatment of patients with unresectable or metastatic melanoma Non-small Cell Lung Cancer Keytruda, as a single agent, is indicated for the first-line treatment of patients with metastatic non-small cell lung cancer (NSCLC) whose tumors have high PD-L1 expression [Tumor Proportion Score (TPS) 50%] as determined by an FDA-approved test, with no EGFR or ALK genomic tumor aberrations Keytruda, as a single agent, is indicated for the treatment of patients with metastatic NSCLC whose tumors express PD-L1 (TPS 1%) as determined by an FDA-approved test with disease progression on or after platinum-based chemotherapy. Keytruda is indicated for Ppatients with EGFR or ALK genomic tumor aberrations should have disease progression on FDA-approved therapy for these aberrations prior to receiving pembrolizumab. Keytruda, in combination with pemetrexed and carboplatin, is indicated for the first-line treatment of patients with metastatic nonsquamous NSCLC. Head and Neck Cancer Keytruda is indicated for the treatment of patients with recurrent or metastatic head and neck squamous cell carcinoma with disease progression on or after platinum-containing chemotherapy Urothelial Carcinoma Keytruda is indicated for the treatment of patients with locally advanced or metastatic urothelial carcinoma who are not eligible for cisplatin-containing chemotherapy
Keytruda 2 Keytruda is indicated for the treatment of patients with locally advanced or metastatic urothelial carcinoma who have disease progression during or following platinum-containing chemotherapy or within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy Microsatellite Instability-High Cancer Keytruda is indicated for the treatment of adult and pediatric patients with unresectable or metastatic, microsatellite instability-high (MSI-H) or mismatch repair deficient o Solid tumors that have progressed following prior treatment and who have no satisfactory alternative treatment options, or o Colorectal cancer that has progressed following treatment with a fluoropyrimidine, oxaliplatin, and irinotecan Compendial Uses Unresectable or metastatic melanoma as a single agent for: o First-line therapy o Second-line or subsequent therapy (if not already given) following disease progression in patients with performance status (PS) 0-2 if anti PD-1 monotherapy not previously used o After maximum clinical benefit from BRAF targeted therapy for patients with PS 0-2 o Re-induction therapy for patients with PS 0-2 who experience disease control and have no residual toxicity but subsequently experience disease (treatment for disease progression/relapse >3 months after treatment discontinuation. and previous response) Merkel cell carcinoma (non-melanoma skin cancer) o Treatment for distant metastatic disease or disseminated recurrence (with or without surgery or radiation therapy [RT]) Non-small cell lung cancer o Single agent therapy for recurrence or metastasis if PD-L1 expression-positive ( 50%) as First-line therapy for tumors that are EGFR, ALK, and ROS1 negative or unknown Subsequent therapy for sensitizing EGFR mutation-positive tumors and prior erlotinib, afatinib, gefitinib, or osimertinib therapy Subsequent therapy for ALK rearrangement-positive tumors and prior crizotinib, ceritinib, or alectinib therapy Subsequent therapy for ROS1 rearrangement-positive tumors and prior crizotinib therapy o Treatment for recurrence or metastasis for tumors of nonsquamous cell histology in combination with carboplatin and pemetrexed (if pembrolizumab not previously given) for patients with performance status 0-1 as first-line therapy for EGFR, ALK, ROS1, BRAF, and PD-L1 negative or unknown first-line or subsequent therapy for BRAF V600E-mutation positive tumors subsequent therapy for sensitizing EGFR mutation-positive tumors and prior erlotinib, afatinib, gefitinib, or osimertinib therapy subsequent therapy for ALK rearrangement-positive tumors and prior crizotinib, ceritinib, alectinib, or brigatinib therapy subsequent therapy for ROS1 rearrangement-positive tumors and prior crizotinib therapy subsequent therapy for PD-L1 expression-positive ( 50%) tumors and EGFR, ALK, ROS1, and BRAF negative or unknown
Keytruda 3 o Single agent as subsequent therapy (if not already given) for metastatic disease in patients with performance status 0-2 and tumors with PD-L1 expression levels 1% Following progression on a first-line cytotoxic regimen For further progression on other systemic therapy Head and neck cancer o Therapy as a single agent if disease progression on or after platinum-containing chemotherapy for: newly diagnosed T4b, any N, M0 disease; unresectable nodal disease with no metastases; or for patients who are unfit for surgery and performance status (PS)3 metastatic (M1) disease at initial presentation or recurrent/persistent disease with distant metastases, or unresectable locoregional recurrence or second primary with prior radiation therapy (RT) and PS 0-2 unresectable locoregional recurrence without prior RT and PS 3e Bladder Cancer o Used as a single agent for Bladder Cancer clinical stage T4b or T2-4a, N1-3 disease, or for recurrence post cystectomy, or for metastatic disease first line therapy in cisplatin ineligible patients subsequent systemic therapy o Used as a single agent for primary treatment for pprimary ccarcinoma of the uurethra clinical stages T3-4 cn1-2 disease or cn1-2 palpable inguinal lymph nodes as first line therapy in cisplatin ineligible patients o Used as single agent for metastatic disease of the uupper GIU ttract ttumors as first line therapy in cisplatin ineligible patients subsequent systemic therapy o Used as single agent for metastatic disease for Urothelial Carcinoma of the Prostate as first line therapy in cisplatin ineligible patients subsequent systemic therapy Patients with PS 3 with newly diagnosed T4b, any N, M0 disease; unresectable nodal disease with no metastases; unresectable locoregional recurrence and no prior RT, or for patients who are unfit for surgery Unresectable locoregional recurrence or second primary in patients with PS 0-2 who have received prior RT Metastatic disease Bone Cancer Ewing Sarcoma, Mesenchymal Chondrosarcoma, Osteaosarcoma, Dedifferentiated Chondrosarcoma, and High Grade Undifferentiated Pleomorphic Sarcoma single-agent therapy for patients with unresectable or metastatic, microsatellite instability-high (MSI-H) or mismatch repair deficient (dmmr) tumors that have progressed following prior treatment and who have no satisfactory alternative treatment options Classical Hodgkin lymphoma o Refractory or relapsed disease, as a single agent for refractory disease if Deauville 4-5 or for relapsed disease in patients previously treated with brentuximab vedotin o Palliative therapy, as a single agent for relapsed or refractory disease in older adults (age >60) CNS Cancers o Limited (1-3) Brain Metastases
Keytruda 4 consider for treatment for recurrent disease as a single agent for brain metastases if active against primary tumor (melanoma and non-small cell lung cancer) o Multiple (>3) Brain Metastases treatment for recurrent stable systemic disease as a single agent for brain metastases if active against primary tumor (melanoma and non-small cell lung cancer) Colorectaln Cancer o Primary treatment as a single agent for unresectable metachronous metastases (defective mismatch repair/high microsatellite instability[dmmr/msi-h] and previous adjuvant FOLFOX (fluorouracil, leucovorin and oxaliplatin) or CapeOX (capecitabine and oxaliplatin) within the past 12 months o Initial therapy as a single agent for patients with unresectable advanced or metastatic disease (defective mismatch repair/high microsatellite instability ([dmmr/msi-h] only) who are not appropriate for intensive therapy o Subsequent therapy as a single agent (if nivolumab or pembrolizumab not previously given) for unresectable advanced or metastatic disease (defective mismatch repair/high microsatellite instability [dmmr/msi-h] only) following previous oxaliplatin- irinotecanand/or fluoropyrimidine-based therapy Classical Hodgkin lymphoma o Refractory or relapsed disease, as a single agent o Palliative therapy, as a single agent Malignant Pleural Mesothelioma o Subsequent systemic therapy as a single agent Merkel cell carcinoma (non-melanoma skin cancer) Treatment for distant metastatic disease or disseminated recurrence (with or without surgery or radiation therapy [RT]) Rectal Cancer Primary treatment as a single agent for unresectable metachronous metastases (defective mismatch repair/high microsatellite instability [dmmr/msi-h] only) and previous adjuvant FOLFOX (fluorouracil, leucovorin, and oxaliplatin) or CapeOX (capecitabine and oxaliplatin) within the past 12 months Initial therapy as a single agent for patients with unresectable advanced or metastatic disease (defective mismatch repair/high microsatellite instability [dmmr/msi-h] only) who are not appropriate for intensive therapy Subsequent therapy as a single agent (if nivolumab or pembrolizumab not previously given) for unresectable advanced or metastatic disease (defective mismatch repair/high microsatellite instability [dmmr/msi-h] only) following previous oxaliplatin- irinotecanand/or fluoropyrimidine-based therapy B. REQUIRED DOCUMENTATION The following information is necessary to initiate the prior authorization review: For initial therapy
Keytruda 5 o Current oncology notes, clinical notes (including previous treatment history), and any pertinent pathology reports and/or imaging studies supporting the diagnosis of unresectable or metastatic melanoma For NSCLC, a copy of the laboratory report with PD-L1 test results must be submitted o For continuation therapy o Documentation demonstrating lack of disease progression on therapy (e.g, clinical notes, laboratory tests, and any pertinent pathology reports and/or imaging studies) C. PRESCRIBER RESTRICTIONS Keytruda must be recommended by an oncologist or a hematologist. D. CRITERIA FOR APPROVAL 1. Melanoma a. Initial authorization of 3 months may be granted for members who are prescribed Keytruda for initial/first-line therapy or for re-induction therapy when the following criteria are met: i. Member has unresectable or metastatic disease ii. Keytruda will be used as a single agent b. Initial authorization of 3 months may be granted for members who are prescribed Keytruda for second-line or subsequent therapy when the following criteria are met: i. Member has unresectable or metastatic disease ii. Keytruda will be used as a single agent iii. Member experienced disease progression following previous therapy or maximum clinical benefit from BRAF targeted therapy. Examples of previous therapy: Nivolumab (Opdivo) Nivolumab (Opdivo)/ipilimumab (Yervoy) Vemurafenib (Zelboraf) Dabrafenib (Tafinlar)/trametinib (Mekinist) 2. Non-small cell lung cancer a. Initial authorization of 3 months may be granted for members who are prescribed Keytruda for first-line therapy or subsequent therapy following targeted therapy only when the following criteria are met: i. Member has metastatic disease, AND ii. Member has non-squamous NSCLC and Keytruda will be used in combination with pemetrexed and carboplatin, OR iii. Tumor has high PD-L1 expression (Tumor Proportion Score [TPS] 50%; a copy of laboratory test result is required), AND iv. Patients with tumors known to have EGFR, ALK or ROS1 genomic aberrations are required to have had progression on an FDA-approved therapy for one of these aberrations, AND v. Keytruda will be used as a single agent b. Initial authorization of 3 months may be granted for members who are prescribed Keytruda for subsequent therapy following chemotherapy or other systemic therapy when the following criteria are met: i. Member has metastatic disease ii. Tumor is positive for PD-L1 expression (TPS 1%; a copy of laboratory test result is required)
Keytruda 6 iii. Keytruda will be used as a single agent iv. Member has experienced disease progression on or after first-line cytotoxic therapy, or further progression of other systemic therapy (documentation with previous therapy must be submitted) 3. Head and neck cancer for head and neck cancer when the following criteria are met: a. Member has recurrent or metastatic disease, or b. Member has any of the following conditions: diagnosed with T4b disease, unresectable nodal disease, or unfit for surgery, and c. Histology is squamous cell carcinoma, and d. Member has experienced disease progression on or after platinum-containing chemotherapy 4. Classical Hodgkin lymphoma for relapsed or refractory Classical Hodgkin lymphoma when the following criteria are met: Member has relapsed or refractory disease, or Keytruda will be used as palliative therapy 5. Urothelial carcinoma for urothelial carcinoma when the following criteria are met: a. Member has locally advanced or metastatic disease, and b. Member meets any of the following (i., ii. Or iii): i. Not eligible to receive cisplatin-containing chemotherapy ii. Experienced disease progression during or following platinum-containing chemotherapy iii. Experienced disease progression within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy 6. Microsatellite instability-high / Mismatch repair deficient cancer for microsatellite instability-high or mismatch repair deficient cancer when the following criteria are met: a. Solid tumor/colorectal cancer has high microsatellite instability or defective mismatch repair b. Cancer is unresectable or metastatic c. Keytruda is not prescribed for a pediatric patient with a central nervous system cancer d. For colorectal cancer: Experienced disease progression following treatment with a fluoropyrimidine, oxaliplatin, and irinotecan regimenno further criteria. e. For other solid tumors: i. Experienced disease progression following previous treatment, and ii. There are no other satisfactory alternative treatment options available 7. Merkel cell carcinoma
Keytruda 7 for Merkel cell carcinoma and have distant metastatic disease or disseminated recurrence. E. CONTINUATION OF THERAPY 1. No previous authorization/precertification: All members (including new members and members currently receiving treatment without prior authorization) must meet criteria for initial approval in section D. 2. Reauthorization: Members who were previously approved for Keytruda by HMSA/CVS may request reauthorizations after their initial approval. Approval for an additional 3 months may be granted if the following information is supplied: A current oncology note documenting the patient s response to treatment showing no progression of disease Current imaging studies and other objective measures showing no progression of disease when compared with previous results Authorization of 3 months may be granted to members requesting authorization for continuation of therapy if Keytruda was previously authorized by HMSA/CVS and documentation supporting lack of disease progression on Keytruda therapy is provided. F. DOSAGE AND ADMINISTRATION Approvals may be subject to dosing limits in accordance with FDA-approved labeling, accepted compendia, and/or evidence-based practice guidelines. G. ADMINISTRATIVE GUIDELINES Precertification is required. Please refer to the HMSA medical policy web site for the fax form. H. IMPORTANT REMINDER The purpose of this Medical Policy is to provide a guide to coverage. This Medical Policy is not intended to dictate to providers how to practice medicine. Nothing in this Medical Policy is intended to discourage or prohibit providing other medical advice or treatment deemed appropriate by the treating physician. Benefit determinations are subject to applicable member contract language. To the extent there are any conflicts between these guidelines and the contract language, the contract language will control. This Medical Policy has been developed through consideration of the medical necessity criteria under Hawaii s Patients Bill of Rights and Responsibilities Act (Hawaii Revised Statutes 432E-1.4), generally accepted standards of medical practice and review of medical literature and government approval status. HMSA has determined that services not covered under this Medical Policy will not be medically necessary under Hawaii law in most cases. If a treating physician disagrees with HMSA s determination as to medical necessity in a given case, the physician may request that CVS/caremark reconsider the application of the medical necessity criteria to the case at issue in light of any supporting documentation.
Keytruda 8 I. REFERENCES 1. Keytruda [package insert]. Whitehouse Station, NJ: Merck & Co., Inc.; May July 2017. 2. National Cancer Comprehensive Network Drugs and Biologics Compendium. Available at http://www.nccn.org. Accessed November 22, 2016August 22 nd 2017. Document History 10/01/2015 Original effective date 02/2016 Added new indication, first-line melanoma 08/2016 Added new indication, head and neck cancer 11/2016 Added new indication, first-line NSCLC 12/2016 Annual update 05/01/2017 Revision effective date 06/2017 Added new/expanded indications: chl, NSCLC, urothelial carcinoma, MSI- H/dMMR solid tumors 07/24/2017 Revision effective date 08/2017 Annual Review 03/01/2018TBD Revision effective date