Cigna Drug and Biologic Coverage Policy

Transcription

1 Cigna Drug and Biologic Coverage Policy Subject Antiemetic Therapy Table of Contents Coverage Policy... 1 General Background... 6 Coding/Billing Information... 8 References... 8 Effective Date... 1/1/2018 Next Review Date... 9/15/2018 Coverage Policy Number Related Coverage Resources Quantity Limitations INSTRUCTIONS FOR USE The following Coverage Policy applies to health benefit plans administered by Cigna Companies. Certain Cigna Companies and/or lines of business only provide utilization review services to clients and do not make coverage determinations. References to standard benefit plan language and coverage determinations do not apply to those clients. Coverage Policies are intended to provide guidance in interpreting certain standard benefit plans administered by Cigna Companies. Please note, the terms of a customer s particular benefit plan document [Group Service Agreement, Evidence of Coverage, Certificate of Coverage, Summary Plan Description (SPD) or similar plan document] may differ significantly from the standard benefit plans upon which these Coverage Policies are based. For example, a customer s benefit plan document may contain a specific exclusion related to a topic addressed in a Coverage Policy. In the event of a conflict, a customer s benefit plan document always supersedes the information in the Coverage Policies. In the absence of a controlling federal or state coverage mandate, benefits are ultimately determined by the terms of the applicable benefit plan document. Coverage determinations in each specific instance require consideration of 1) the terms of the applicable benefit plan document in effect on the date of service; 2) any applicable laws/regulations; 3) any relevant collateral source materials including Coverage Policies and; 4) the specific facts of the particular situation. Coverage Policies relate exclusively to the administration of health benefit plans. Coverage Policies are not recommendations for treatment and should never be used as treatment guidelines. In certain markets, delegated vendor guidelines may be used to support medical necessity and other coverage determinations. Coverage Policy Cigna covers antiemetic therapy as medically necessary when the following criteria are met: Product Criteria for Use Akynzeo Cigna covers Akynzeo (palonosetron/ neupitant) as medically necessary for an (palonosetron/ adult in combination with dexamethasone for the prevention of nausea and netupitant capsules) vomiting for intravenous antineoplastic therapy meeting either of the following: High emetic risk Moderate emetic risk Aloxi (palonosetron Anzemet (dolasetron tablets) When criteria are met, a maximum of 4 capsules will be allowed per 28 days. Cigna covers Aloxi (palonosetron) as medically necessary in an adult for any of the following: Prevention of nausea and vomiting in combination with dexamethasone for intravenous antineoplastic therapy meeting either of the following: o High emetic risk o Moderate emetic risk Prevention of post-operative nausea and vomiting (PONV) for up to 24 hours following surgery Cigna covers Aloxi (palonosetron) as medically necessary in a pediatric individual for the prevention of nausea and vomiting associated with cancer chemotherapy. Cigna covers Anzemet (dolasetron tablets) as medically necessary for an individual 2 years and older for either of the following: Prevention or treatment of nausea and vomiting associated with cancer Page 1 of 9

2 Product (aprepitant capsules, suspension) Criteria for Use chemotherapy. Prevention of post-operative nausea and vomiting (PONV) Cigna covers (aprepitant) as medically necessary in an adult when both of the following are met: ONE of the following: o Prevention of nausea and vomiting in combination with dexamethasone for intravenous antineoplastic therapy that has high or moderate emetic risk o Prevention of post-operative nausea and vomiting (PONV) in an adult Documented intolerance or inability to use generic aprepitant capsules Cigna covers (aprepitant) as medically necessary in a pediatric individual when both of the following are met: Prevention of nausea and vomiting associated with cancer chemotherapy For individuals 12 years of age and older: Documented intolerance or inability to use generic aprepitant capsules (fosaprepitant Sancuso transdermal) Sustol extended-release Varubi (rolapitant tablets) When criteria are met, the following maximum quantities will be allowed: Capsules: Up to 4 treatment cycles (one 125mg capsule and two 80mg capsules) per 28 days OR one 40 mg capsule per 28 days Suspension: 12 packets per 28 days (3 packets per week) Cigna covers (fosaprepitant) as medically necessary for an adult in combination with dexamethasone for the prevention of nausea and vomiting for intravenous antineoplastic therapy meeting either of the following: High emetic risk Moderate emetic risk Cigna covers Sancuso transdermal) as medically necessary for an adult for either of the following: Prevention of nausea and vomiting for either of the following: o High or moderate emetic risk intravenous antineoplastic therapy in combination with dexamethasone o High or moderate emetic risk oral antineoplastic therapy Breakthrough treatment of chemotherapy-induced nausea/vomiting When criteria are met, a maximum of 4 patches will be allowed per 30 days. Cigna covers Sustol extended-release) as medically necessary for an adult in combination with dexamethasone for the prevention of nausea and vomiting for intravenous antineoplastic therapy meeting either of the following: High emetic risk AND Sustol will be used in combination with an NK1 receptor antagonist (i.e., aprepitant, fosaprepitant, rolapitant) Moderate emetic risk Cigna covers Varubi (rolapitant) as medically necessary for an adult in combination with dexamethasone for the prevention of nausea and vomiting for intravenous antineoplastic therapy meeting either of the following: High emetic risk Moderate emetic risk When criteria are met, a maximum of 4 tablets (2 doses) will be allowed per 28 days. Cigna does not cover the use of antiemetic therapy for any other indication because it is considered experimental, investigational or unproven. When coverage is available and medically necessary, the dosage, frequency, duration of therapy, and site of care should be reasonable, clinically appropriate, and supported by evidence-based literature and adjusted based upon severity, alternative available treatments, and previous response to antiemetic therapy. Page 2 of 9

3 Note: Receipt of sample product does not satisfy any criteria requirements for coverage FDA Approved Indication Product Akynzeo (palonosetron/ netupitant) Aloxi (palonosetron) FDA Approved Indication Akynzeo is indicated for the prevention of acute and delayed nausea and vomiting associated with initial and repeat courses of cancer chemotherapy, including, but not limited to, highly emetogenic chemotherapy. Akynzeo is an oral fixed combination of palonosetron and netupitant: palonosetron prevents nausea and vomiting during the acute phase and netupitant prevents nausea and vomiting during both the acute and delayed phase after cancer chemotherapy. Chemotherapy-Induced Nausea and Vomiting in Adults Aloxi is indicated for: Moderately emetogenic cancer chemotherapy -- prevention of acute and delayed nausea and vomiting associated with initial and repeat courses Highly emetogenic cancer chemotherapy -- prevention of acute nausea and vomiting associated with initial and repeat courses Chemotherapy-Induced Nausea and Vomiting in Pediatric Patients Aged 1 month to Less than 17 Years Aloxi is indicated for prevention of acute nausea and vomiting associated with initial and repeat courses of emetogenic cancer chemotherapy, including highly emetogenic cancer chemotherapy. Postoperative Nausea and Vomiting in Adults Aloxi is indicated for prevention of postoperative nausea and vomiting (PONV) for up to 24 hours following surgery. Efficacy beyond 24 hours has not been demonstrated. Anzemet (dolasetron) (aprepitant) As with other antiemetics, routine prophylaxis is not recommended in patients in whom there is little expectation that nausea and/or vomiting will occur postoperatively. In patients where nausea and vomiting must be avoided during the postoperative period, Aloxi is recommended even where the incidence of postoperative nausea and/or vomiting is low. Anzemet Tablets are indicated for the prevention of nausea and vomiting associated with moderately emetogenic cancer chemotherapy, including initial and repeat courses in adults and children 2 years and older. Prevention of Chemotherapy Induced Nausea and Vomiting (CINV) for oral suspension, in combination with other antiemetic agents, is indicated in patients 6 months of age and older for the prevention of: acute and delayed nausea and vomiting associated with initial and repeat courses of highly emetogenic cancer chemotherapy (HEC) including high-dose cisplatin. nausea and vomiting associated with initial and repeat courses of moderately emetogenic cancer chemotherapy (MEC). capsules, in combination with other antiemetic agents, is indicated in patients 12 years of age and older for the prevention of: acute and delayed nausea and vomiting associated with initial and repeat courses of highly emetogenic cancer chemotherapy (HEC) including high-dose cisplatin. nausea and vomiting associated with initial and repeat courses of moderately emetogenic cancer chemotherapy (MEC). Prevention of Postoperative Nausea and Vomiting (PONV) capsules are indicated in adults for the prevention of postoperative nausea and vomiting. Limitations of Use has not been studied for the treatment of established nausea and vomiting. Chronic continuous administration of EMEND is not recommended because it has not Page 3 of 9

4 Product (fosaprepitant) Sancuso transdermal) Sustol extended-release Varubi (rolapitant) FDA Approved Indication been studied, and because the drug interaction profile may change during chronic continuous use. for injection, in combination with other antiemetic agents, is indicated in adults for the prevention of: acute and delayed nausea and vomiting associated with initial and repeat courses of highly emetogenic cancer chemotherapy (HEC) including high-dose cisplatin. delayed nausea and vomiting associated with initial and repeat courses of moderately emetogenic cancer chemotherapy (MEC). Limitations of Use has not been studied for the treatment of established nausea and vomiting. Sancuso transdermal system) is indicated for the prevention of nausea and vomiting in patients receiving moderately and/or highly emetogenic chemotherapy regimens of up to 5 consecutive days duration. Sustol is indicated in combination with other antiemetics in adults for the prevention of acute and delayed nausea and vomiting associated with initial and repeat courses of moderately emetogenic chemotherapy (MEC) or anthracycline and cyclophosphamide (AC) combination chemotherapy regimens. Varubi is indicated in combination with other antiemetic agents in adults for the prevention of delayed nausea and vomiting associated with initial and repeat courses of emetogenic cancer chemotherapy, including, but not limited to, highly emetogenic chemotherapy. FDA Recommended Dosing Product Akynzeo (palonosetron/ netupitant) FDA Recommended Dosing Highly Emetogenic Chemotherapy, including Cisplatin Based Chemotherapy The recommended dosage in adults is one capsule of Akynzeo administered approximately 1 hour prior to the start of chemotherapy with dexamethasone 12 mg administered orally 30 minutes prior to chemotherapy on day 1 and 8 mg orally once daily on days 2 to 4 [see Clinical Studies (14),Table 5]. Anthracyclines and Cyclophosphamide Based Chemotherapy and Chemotherapy Not Considered Highly Emetogenic The recommended dosage in adults is one capsule of Akynzeo approximately 1 hour prior to the start of chemotherapy with dexamethasone 12 mg administered orally 30 minutes prior to chemotherapy on day 1. Administration of dexamethasone on days 2 to 4 is not necessary [see Clinical Studies (14), Table 7]. Aloxi (palonosetron) Anzemet (dolasetron) Akynzeo can be taken with or without food. Recommended Dosing Chemotherapy-Induced Nausea and Vomiting Age Dose* Infusion Time Adults 0.25 mg x 1 Infuse over 30 seconds beginning approx.. 30 min before the start of chemo Pediatrics (1 month 20 micrograms per Infuse over 15 minutes beginning approx. to less than 1 years) kilogram (max min before the start of chemo mg) x 1 * Note different dosing units in pediatrics Postoperative Nausea and Vomiting Dosage for Adults - a single mg intravenous dose administered over 10 seconds immediately before the induction of anesthesia. The recommended doses of Anzemet Tablets should not be exceeded. Adults The recommended oral dosage of Anzemet (dolasetron mesylate) is 100 mg given within one hour before chemotherapy. Page 4 of 9

5 Product FDA Recommended Dosing Pediatric Patients The recommended oral dosage in pediatric patients 2 to 16 years of age is 1.8 mg/kg given within one hour before chemotherapy, up to a maximum of 100 mg. Safety and effectiveness in pediatric patients under 2 years of age have not been established. In children for whom the 100 mg tablet is not appropriate based on their weight or ability to swallow tablets, the Anzemet Injection solution may be mixed into apple or apple-grape juice for oral dosing in pediatric patients. The diluted product may be kept up to 2 hours at room temperature before use. However, Anzemet Injection solution when administered intravenously is contraindicated in adult and pediatric patients for the prevention of nausea and vomiting associated with initial and repeat courses of emetogenic cancer chemotherapy due to dose dependent QT prolongation. (aprepitant) (fosaprepitant) Sancuso transdermal) Sustol extendedrelease Use in the Elderly, Renal Failure Patients, or Hepatically Impaired Patients No dosage adjustment is recommended, however; ECG monitoring is recommended for elderly and renally impaired patients (see WARNINGS and CLINICAL PHARMACOLOGY, Pharmacokinetics in Humans). **Refer to the prescribing information (product label) for complete dosing information. The following is from the Highlights of Prescribing Information section of the product label Recommended Dosage for Prevention of Chemotherapy Induced Nausea and Vomiting (CINV) capsules in adults and pediatric patients 12 years of age and older: is 125 mg on Day 1 and 80 mg on Days 2 and 3. for oral suspension in pediatric patients 6 months to less than 12 years of age or pediatric and adult patients unable to swallow capsules: see dosing recommendations in Table 3 in the Full Prescribing Information. Administer 1 hour prior to chemotherapy on Days 1, 2, and 3. If no chemotherapy is given on Days 2 and 3, administer in morning. See Full Prescribing Information for recommended dosages of concomitant dexamethasone and 5-HT3 antagonist for HEC and MEC. Recommended Dosage for PONV Adults: 40 mg capsules within 3 hours prior to induction of anesthesia. **Refer to the prescribing information (product label) for complete dosing information. The following is from the Highlights of Prescribing Information section of the product label Recommended dosage in adults is 150 mg on Day 1 as an intravenous infusion over 20 to 30 minutes approximately 30 minutes prior to chemotherapy. See Full Prescribing Information for recommended dosages of concomitant dexamethasone and a 5-HT3 antagonist for HEC and MEC. The transdermal system (patch) should be applied to clean, dry, intact healthy skin on the upper outer arm. Sancuso should not be placed on skin that is red, irritated or damaged. Each patch is packed in a pouch and should be applied directly after the pouch has been opened. The patch should not be cut into pieces. Adults Apply a single patch to the upper outer arm a minimum of 24 hours before chemotherapy. The patch may be applied up to a maximum of 48 hours before chemotherapy as appropriate. Remove the patch a minimum of 24 hours after completion of chemotherapy. The patch can be worn for up to 7 days depending on the duration of the chemotherapy regimen. The recommended dosage of Sustol is 10 mg administered subcutaneously. Administer Sustol in combination with dexamethasone at least 30 minutes before the initiation of MEC or AC combination chemotherapy. Administer Sustol on Day 1 of chemotherapy and not more frequently than once every 7 days because of the extended-release properties of the formulation. Page 5 of 9

6 Product FDA Recommended Dosing For patients receiving MEC, the recommended dexamethasone dosage is 8 mg intravenously on Day 1. For patients receiving AC combination chemotherapy regimens, the recommended dexamethasone dosage is 20 mg intravenously on Day 1, followed by 8 mg orally, twice a day, on Days 2, 3 and 4. Varubi (rolapitant) If Sustol is administered with an NK1 receptor antagonist, see the prescribing information of the NK1 receptor antagonist for the recommended dexamethasone dosage. **Refer to the prescribing information (product label) for complete dosing information. The following is from the Highlights of Prescribing Information section of the product label The recommended dosage is 180 mg rolapitant administered approximately 1 to 2 hours prior to the start of chemotherapy. Administer in combination with dexamethasone and a 5-HT3 receptor antagonist, see full prescribing information for dosing information. No dosage adjustment for dexamethasone is required. Drug Availability Product Akynzeo (palonosetron/ netupitant) Aloxi (palonosetron) Drug Availability Akynzeo (300 mg netupitant/0.5 mg palonosetron) capsules are available as a pack of either 1 capsule or 4 capsules. Aloxi is supplied as a single-use sterile, clear, colorless solution in glass vials that provide: 0.25 mg (free base) per 5 ml (concentration: 0.05 mg/ml, 50 mcg/ml) mg (free base) per 1.5 ml (concentration: 0.05 mg/ml, 50 mcg/ml) Anzemet (dolasetron) (aprepitant) (fosaprepitant) Sancuso transdermal) Sustol extended-release Varubi (rolapitant) Aloxi capsules have been discontinued by the manufacturer. Anzemet tablets are available as 50mg and 100mg and packaged as either 5 count or 10 count. Anzemet injection has been discontinued by the manufacturer. capsules are available as 40mg, 80mg, and 125mg. The 40mg capsules are packaged as either 1 capsule or 5 capsules; 80mg are packaged as either 2 or 6 capsules; 125mg are packaged as 6 capsules. There is also a package of one 125mg and two 80mg capsules. for oral suspension is available as a single use pouch of 125mg powder and should be prepared by a healthcare provider. for injection is available as 150 mg of fosaprepitant, white to off-white lyophilized powder in single-dose glass vial for reconstitution. Sancuso is a 52 cm2 patch containing 34.3 mg of granisetron. The patch releases 3.1 mg of granisetron per 24 hours for up to 7 days. Sancuso is available in packages of 1 patch. Sustol extended-release injection is supplied in cartons of six kits; single dose kit contains: One sterile single-dose amber colored glass syringe which contains 10 mg granisetron/0.4 ml, One sterile 18 Ga 5/8 special thin walled administration needle, Two sodium acetate syringe warming pouches, One Point Lok needle protection device. Varubi is available as: Tablets containing 90 mg rolapitant and supplied as a single dose package (2 tablets as one set of twinned blisters) General Background Pharmacology Page 6 of 9

7 Aprepitant (), fosaprepitant (), and rolapitant (Varubi) are a substance P/neurokinin 1 (NK1) receptor antagonists. Dolasetron (Anzemet), palonosetron (Aloxi), granisetron (Sustol) are selective serotonin-3 (5-HT3) receptor antagonists. Akynzeo is a combination product of a 5-HT3 receptor antagonist (palonosetron) and an NK1 receptor antagonis (netupitant). Guidelines National Comprehensive Cancer Network (NCCN) NCCN provides recommendations for antiemetic therapy regimens based on the emetogenic risk of the chemotherapy and if it is intravenous or oral. The emetogenic risk of intravenous antineoplastics is based on the frequency of emesis. High emetic risk agents have a greater than 90% frequency of emesis (an example includes combination regimens that contain an anthracycline and cyclophosphamide). Moderate emetic risk has a 30-90% frequency of emesis while low emetic risk and minimal emetic risk have a 10-30% and less than 10% frequency of emesis, respectively. For oral antineoplastic agents, the levels are divided into those with moderate to high emetic risk (greater than or equal to 30% frequency of emesis) and minimal to low emetic risk (less than 30% frequency of emesis). (NCCN, 2017) For high emetic risk intravenous (IV) chemotherapy, NCCN recommends several options for acute and delayed emesis prevention without a preference given to one regimen over another. Regimens recommended include either aprepitant oral, fosaprepitant IV, or rolapitant oral in combination with a 5-HT3 receptor antagonist (palonosetron IV; granisetron subcutaneous [SQ], oral, IV or transdermal; ondansetron oral or IV; or dolasetron oral) with dexamethasone. Other options include netupitant/palonosetron oral in combination with dexamethasone; olanzapine oral with palonosetron IV and dexamethasone; or aprepitant oral or fosaprepitant IV in combination with a 5-HT3 receptor antagonist, dexamethasone, and olanzapine. (NCCN, 2017) For moderate emetic risk IV chemotherapy, several options are recommended without preference for acute and delayed emesis prevention. One option recommends a 5-HT3 receptor antagonist in combination with dexamethasone. NCCN notes a preference for palonosetron IV or granisetron SQ when a 5-HT3 receptor antagonist is not used in combination with an NK1 antagonist. Other options include use of aprepitant oral, fosaprepitant IV, rolapitant oral in combination with a 5-HT3 receptor antagonist and dexamethasone; netupitant/palonosetron oral in combination with dexamethasone; or olanzapine oral with palonosetron IV and dexamethasone. (NCCN, 2017) Emesis prevention for low emetic risk IV chemotherapy includes use of dexamethasone; metoclopramide; prochlorperazine; or an oral 5-HT3 receptor antagonist. There is not routine prophylaxis recommended for minimal emetic risk IV chemotherapy. (NCCN, 2017) For emesis prevention with oral chemotherapy, NCCN recommends a 5-HT3 receptor antagonist (dolasetron oral; granisetron oral or transdermal; or ondansetron oral) for high to moderate emetic risk therapy. As needed treatment is recommended initially for low to minimal emetic risk with recommendations provided when nausea/vomiting is experienced. (NCCN, 2017) If breakthrough chemotherapy-induced nausea and vomiting occurs, recommendations for subsequent chemotherapy cycles include changing the antiemetic regimen to a higher level for primary treatment. (NCCN, 2017) American Society of Clinical Oncology (ASCO) For adults receiving high-emetic risk antineoplastic therapy (cisplatin and other high-emetic risk single agents or anthracycline combined with cyclophosphamide), ASCO recommends a 4-drug combination, including a NK1 antagonist, 5-HT3 receptor antagonist, dexamethasone, and olanzapine. For moderate-emetic risk antineoplastic therapy with carboplatin (area under the curve [AUC] greater than or equal to 4 mg/ml per minute), ASCO recommends a 3-drug combination of NK1 antagonist, 5-HT3 receptor antagonist, and dexamethasone. A 2-drug regimen of 5-HT3 receptor antagonist and dexamethasone is recommended for moderate-emetic risk antineoplastic therapy excluding carboplatin AUC greater than or equal to 4 mg/ml per minute. ASCO recommends a single dose of 5-HT3 receptor antagonist or single dose of dexamethasone before low-emetic risk antineoplastic treatment and no routine antiemetic prophylaxis for minimal-emetic risk. For breakthrough nausea and vomiting, ASCO recommends adding olanzapine to the standard antiemetic regimen (if no previously included) and offering a drug of a different class. Recommendations for high emetic Page 7 of 9

8 risk radiation therapy include use of a 5-HT3 receptor antagonist with or without dexamethasone or a dopamine receptor antagonist. (Hesketh, 2017) ASCO provides recommendations for pediatric patients. For high-emetic risk antineoplastic therapy, a 3-drug combination of 5-HT3 receptor antagonist, dexamethasone, and aprepitant (if able to receive) is recommended. For those unable to receive dexamethasone, a 2-drug combination of palonosetron and aprepitant is advised. For moderate-emetic risk, a 5-HT3 receptor antagonist and dexamethasone is recommended and for those unable to receive dexamethasone, a combination of a 5-HT3 receptor antagonist and aprepitant. For lowemetic risk, ondansetron or granisetron should be given and no routine prophylaxis is recommended for minimal emetic risk. (Hesketh, 2017) Clinical Efficacy Dolasetron Tablets for the Prevention of Post-Operative Nausea and Vomiting (PONV) The AHFS supports the use of dolasetron tablets (Anzemet) for the prevention of post-operative nausea and vomiting based on several randomized, double-blind, placebo-controlled studies. (AHFS, 2017) Coding/Billing Information Note: Akynzeo (palonosetron/netupitant), Anzemet (dolasetron), (aprepitant), Sancuso transdermal), and Varubi (rolapitant) are typically covered under pharmacy benefit plans. Certain prescription drugs require an authorization for coverage to ensure that appropriate treatment regimens are followed. Medical drug coding and diagnosis codes, however, are generally not required for pharmacy claims submissions. Aloxi (palonsetron) and Sustol extended-release requires medical drug coding and is listed as follows: Note: 1) This list of codes may not be all-inclusive. 2) Deleted codes and codes which are not effective at the time the service is rendered may not be eligible for reimbursement. Covered when medically necessary: HCPCS Description Codes C9486 Injection, granisetron extended release, 0.1 mg (Code deleted 12/31/2017) J1453 Fosaprepitant injection J1627 Injection, granisetron, extended-release, 0.1 mg (Code effective 01/01/2018) J2469 Palonosetron HCl References 1. Eisai Inc. Aloxi (palonosetron HCl) injection for intravenous use [product information]. Woodcliff Lake, NJ: Eisai Inc. September Helsinn Therapeutics (U.S.), Inc. Akynzeo (netupitant and palonosetron) capsules, for oral use [product information]. Iselin, NJ: Helsinn Therapeutics (U.S.), Inc. December Heron Therapeutics. Sustol extended-release injection, for subcutaneous use) [product information]. Redwood City, CA: Heron Therapeutics. August Hesketh PJ, Kris MG, Basch E, et al. Antiemetics: American Society of Clinical Oncology Clinical Practice Guideline Update. J Clin Oncol 2017; 35: Merck & Co., Inc. (aprepitant) capsules, for oral use and (aprepitant) for oral suspension [product information]. Whitehouse Station, NJ: Merck & Co., Inc. May Page 8 of 9

9 6. Merck & Co., Inc. (fosaprepitant) capsules, for injection, for intravenous use [product information]. Whitehouse Station, NJ: Merck & Co., Inc. May McEvoy GK, ed. American Hospital Formulary Service 2017 Drug Information. Bethesda, MD: American Society of Health-Systems Pharmacists, Inc National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines in Oncology (NCCN Guidelines ): Antiemesis V2.2017; [available with free subscription] Updated March 28, Accessed July 18, ProStrakan Inc. Sancuso transdermal system) [product information]. Bedminster, NJ: ProStrakan Inc. September sanofi-aventis U.S. LLC. Anzemet Tablets (dolasetron mesylate) [product information]. Bridgewater, NJ: sanofi-aventis U.S. LLC. September TESARO, Inc. Varubi (rolapitant) tablets, for oral use [product information]. Waltham, MA: TESARO, Inc. September Cigna Companies refers to operating subsidiaries of Cigna Corporation. All products and services are provided exclusively by or through such operating subsidiaries, including Cigna Health and Life Insurance Company, Connecticut General Life Insurance Company, Cigna Behavioral Health, Inc., Cigna Health Management, Inc., QualCare, Inc., and HMO or service company subsidiaries of Cigna Health Corporation. The Cigna name, logo, and other Cigna marks are owned by Cigna Intellectual Property, Inc Cigna. Page 9 of 9