CAM 106

Nivolumab (Opdivo)

Category:Prescription Drug   Last Reviewed:June 2021
Department(s):Medical Affairs   Next Review:June 2022
Original Date:June 2015    

Description:
Nivolumab (Opdivo) is a human programmed death receptor (PD-1)-blocking antibody. It enhances the antitumor response by binding to PD-1 receptors and blocking its interaction with PD-L1 and PD-L2.

Policy:
OPDIVO is a programmed death receptor-1 (PD-1) blocking antibody indicated for the treatment of: 

  • patients with BRAF V600 wild-type unresectable or metastatic melanoma, as a single agent.  
  • patients with BRAF V600 mutation-positive unresectable or metastatic melanoma, as a single agent.a  
  • patients with unresectable or metastatic melanoma, in combination with ipilimumab.a 
  • patients with melanoma with lymph node involvement or metastatic disease who have undergone complete resection, in the adjuvant setting.  
  • patients with metastatic non-small cell lung cancer and progression on or after platinum-based chemotherapy. Patients with EGFR or ALK genomic tumor aberrations should have disease progression on FDA-approved therapy for these aberrations prior to receiving OPDIVO.  
  • patients with advanced renal cell carcinoma who have received prior anti-iangiogenic therapy.  
  • adult patients with classical Hodgkin lymphoma that has relapsed or progressed afterb:   ď‚·
    • autologous hematopoietic stem cell transplantation (HSCT) and brentuximab vedotin, or 
    • 3 or more lines of systemic therapy that includes autologous HSCT. 
  • patients with recurrent or metastatic squamous cell carcinoma of the head and neck with disease progression on or after a platinum-based therapy.
  • patients with locally advanced or metastatic urothelial carcinoma whob 
    • have disease progression during or following platinum-containing chemotherapy 
    • have disease progression within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy.  
  • adult and pediatric (12 years and older) patients with microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) metastatic colorectal cancer that has progressed following treatment with a fluoropyrimidine, oxaliplatin, and irinotecan.b   
  • patients with hepatocellular carcinoma who have been previously treated with sorafenib.   
  • patients with intermediate or poor risk, previously untreated advanced renal cell carcinoma in combination with ipilimumab 
  • patients with metastatic small cell lung cancer with progression after platinum-based chemotherapy and at least one other line of therapy.

Compendial Uses: 

  • classical Hodgkin lymphoma 
  • renal cell carcinoma 
  • malignant pleural mesothelioma 
  • NSCLC 
  • small cell lung cancer   

a  This indication is approved under accelerated approval based on progression-free survival. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials. 

b  This indication is approved under accelerated approval based on overall response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical  benefit in confirmatory trials.

BlueCross BlueShield of South Carolina recognizes uses and indications of injectable oncology medications (including chemotherapy/systemic therapy, therapeutic radiopharmaceuticals, and selected supportive therapies) to be medically necessary if they are listed in the NCCN Drugs and Biologics Compendium with Categories of Evidence + Consensus of 1, 2A and 2B. Treatments listed with a Category of Evidence and Consensus of 3 are considered unproven and not medically necessary.

Rationale:
The safety and efficacy of nivolumab were evaluated in a randomized, open-label phase 3 trial (CheckMate-37) of subjects with unresectable (Stage IIIc) or metastatic (Stage IV) melanoma and disease progression following ipilimumab and, if BRAF V600 mutation‒positive, a BRAF inhibitor. Subjects were randomized to receive nivolumab 3 mg/kg every two weeks (n=268) or investigator’s choice of chemotherapy (n=102), either dacarbazine or carboplatin plus paclitaxel. The primary endpoints were objective response rate (ORR) and overall survival. Efficacy was assessed in a single-arm, noncomparative, preplanned interim analysis in the first 120 patients who received nivolumab in Trial 1 and in whom the minimum duration of follow-up was six months.

At six months, the primary endpoint of ORR in the 120 patients who received nivolumab was 32 percent (four complete and 34 partial responses), with 87 percent having a response duration of 2.6 to more than 10 months. The ORR included patients with and without BRAF V600 mutation-positive disease. Evidence of a clinical benefit outside of tumor response rate has not been established. The median duration of exposure was 5.3 months (range, one day to 13.8+ months), with a median of eight doses (range, one-31) in nivolumab-treated patients, and was two months (range, one day to 9.6+ months) in chemotherapy-treated patients. In this ongoing trial, 24 percent of patients received nivolumab for more than six months, and 3 percent of patients received nivolumab for more than one year.

Nivolumab was discontinued for adverse reactions in 9 percent of patients, while 26 percent of patients receiving nivolumab had a drug delay for an adverse reaction. The most common adverse reaction (reported in at least 20 percent of patients) was rash.

Nivolumab’s efficacy to treat squamous NSCLC was established in a randomized trial of 272 participants, of whom 135 received nivolumab and 137 received docetaxel. The trial was designed to measure the amount of time participants lived after starting treatment (overall survival). On average, participants who received nivolumab lived 3.2 months longer than those participants who received docetaxel.

The safety and efficacy of nivolumab to treat squamous NSCLC was supported by a single-arm trial of 117 participants who had progressed after receiving a platinum-based therapy and at least one additional systemic regimen. The study was designed to measure objective response rate (ORR), or the percentage of participants who experienced partial shrinkage or complete disappearance of the tumor. Results showed 15 percent of participants experienced ORR, of whom 59 percent had response durations of six months or longer.

National Comprehensive Cancer Network (NCCN) Guidelines for Melanoma (Version 3.2015) recommend nivolumab for treatment of metastatic or unresectable melanoma in all patients as first-line therapy and as second-line or subsequent therapy in patients with a performance status of 0-2 who have failed treatment with a BRAF inhibibitor. 

References:

  1. Opdivo® Prescribing Information. BMS. Princeton, NJ. December 2014.
  2. Opdivo® Dossier. BMS. Princeton, NJ. December 2014.
  3. AHFS Drug Information. Bethesda (MD): American Society of Health-System Pharmacists, Inc; 2015 [cited 2015-02-12]. In: STAT!Ref Online Electronic Medical Library [Internet]. Available from: http://online.statref.com/.
  4. Clinical Pharmacology [Internet]. Tampa (FL): Gold Standard, Inc.; 2015 [cited 2015-02-12]. Available from: http://www.clinicalpharmacology.com/.
  5. ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine; 2000 Feb 29 - [cited 2015-02-12]. Available from: http://clinicaltrials.gov/.
  6. DRUGDEX® System [Internet]. Greenwood Village (CO): Thomson Micromedex; Updated periodically [cited 2015-02-12]. Available from: http://www.thomsonhc.com/.
  7. E.R. Squibb & Sons, LLC. Opdivo (nivolumab) injection. 2014 [cited 2015-02-12]. In: DailyMed [Internet]. Bethesda (MD): National Library of Medicine. Available from: http://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=f570b9c4-6846-4de2-abfa-4d0a4ae4e394/.
  8. National Comprehensive Cancer Network®. NCCN clinical practice guidelines in oncology (NCCN Guidelines®). Melanoma, v. 2.2015 [cited 2015-02-12]. Available from: http://www.nccn.org/professionals/physician_gls/f_guidelines.asp.
  9. NCCN Drugs & Biologics Compendium [Internet]. Fort Washington (PA): National Comprehensive Cancer Network; 2015 [cited 2015-02-12]. Available from: http://www.nccn.org/professionals/drug_compendium/content/contents.asp/.
  10. Orphan Drug Designations and Approval [Internet]. Silver Spring (MD): US Food and Drug Administration; 2015 [cited 2015-02-12]. Available from: http://www.accessdata.fda.gov/scripts/opdlisting/oopd/index.cfm/.

Coding Section:

Codes

Number

Description 

HCPCS 

C9399 

Unclassified drugs or biologicals

 

J3490 

Unclassified drugs 

 

J9299

Injection, nivolumab, 1 mg 

 

J9999 

Not otherwise classified, antinoplastic drugs 

 ICD-10 CM

C00.0 – C08.9

Malignant neoplasm of lip, base of tongue, of other and unspecified parts of tongue, gum, floor of mouth, palate, of other and unspecified parts of mouth, parotid and salivary gland.

 

C09.0 – C10.9

Malignant neoplasm of tonsil and oropharynx

 

C11.0 – C11.9

Malignant neoplasm of nasopharynx

 

C12.0 – C14.8

Malignant neoplasm of piriform sinus, hypopharynx and other and ill-defined sites in the lip, oral cavity and pharynx.

 

C15.3 – C15.9

Malignant neoplasm of esophagus

 

C30.0

Malignant neoplasm of nasal cavity

 

C31.0 – C31.9

Malignant neoplasm of accessory sinuses

 

C32.0 – C32.9

Malignant neoplasm of larynx

 

C33

Malignant neoplasm of trachea

 

C34.00 – C34.02

Malignant neoplasm of unspecified main bronchus

 

C34.10 – C34.12

Malignant neoplasm of upper lobe, unspecified bronchus or lung

 

C34.2

Malignant neoplasm of middle lobe, bronchus or lung

 

C34.30 – C34.32

Malignant neoplasm of lower lobe, unspecified bronchus or lung

 

C34.80 – C34.82

Malignant neoplasm of overlapping sites of unspecified bronchus and lung

 

C34.90 – C34.92

Malignant neoplasm of unspecified part of unspecified bronchus or lung

 

C38.4

Malignant neoplasm of pleura

 

C43.0

Malignant melanoma of lip

 

C43.10

Malignant melanoma of unspecified eyelid, including canthus

 

C43.11

Malignant melanoma of right eyelid, including canthus

 

C43.12

Malignant melanoma of left eyelid, including canthus

 

C43.20

Malignant melanoma of unspecified ear and external auricular canal

 

C43.21

Malignant melanoma of right ear and external auricular canal

 

C43.22

Malignant melanoma of left ear and external auricular canal

 

C43.30

Malignant melanoma of unspecified part of face

 

C43.31

Malignant melanoma of nose

 

C43.39

Malignant melanoma of other parts of face

 

C43.4

Malignant melanoma of scalp and neck

 

C43.51

Malignant melanoma of anal skin

 

C43.52

Malignant melanoma of skin of breast

 

C43.59

Malignant melanoma of other part of trunk

 

C43.60

Malignant melanoma of unspecified upper limb, including shoulder

 

C43.61

Malignant melanoma of right upper limb, including shoulder

 

C43.62

Malignant melanoma of left upper limb, including shoulder

 

C43.70

Malignant melanoma of unspecified lower limb, including hip

 

C43.71

Malignant melanoma of right lower limb, including hip

 

C43.72

Malignant melanoma of left lower limb, including hip

 

C43.8

Malignant melanoma of overlapping sites of skin

 

C43.9

Malignant melanoma of skin, unspecified

 

C44.00

Malignant neoplasm of skin of lip

 

C44.02

Squamous cell carcinoma of skin of lip

 

C44.09

Other specified malignant neoplasm of skin of lip

 

C45.0

Mesotheothlioma of pleura

 

C61

Malignant neoplasm of prostate (urothelial carcinoma)

 

C64.1 – C64.9

Malignant neoplasm of unspecified kidney, except renal pelvis

 

C65.1 – C65.9

Malignant neoplasm of unspecified renal pelvis

 

C66.1 – C66.9

Malignant neoplasm of ureter

 

C67.0 – C67.9

Malignant neoplasm of bladder

 

C68.0 – C68.9

Malignant neoplasm of other and unspecified urinary organs

 

C69.90

Malignant neoplasm of unspecified site of unspecified eye

 

C69.91

Malignant neoplasm of unspecified site of right eye

 

C69.92

Malignant neoplasm of unspecified site of left eye

 

C76.0

Malignant neoplasm of head, face and neck

 

C77.0

Secondary and unspecified malignant neoplasm of lymph nodes of head, face and neck

 

C78.00 – C78.89

Secondary malignant neoplasm of respiratory and digestive organs

 

C79.31

Secondary malignant neoplasm of brain

 

C79.51-C79.52

Secondary malignant neoplasm of bone and bone marrow

 

C80.0

Disseminated malignant neoplasm, unspecified

 

C80.1

Malignant (primary) neoplasm, unspecified

 

C81.10 – C81.99

Hodgkin Lymphoma

 

D37.01

Neoplasm of uncertain behavior of lip

 

D37.02

Neoplasm of uncertain behavior of tongue

 

D37.04

Neoplasm of uncertain behavior of the minor salivary glands

 

D37.05

Neoplasm of uncertain behavior of pharynx

 

D37.09

Neoplasm of uncertain behavior of other specified sites of the oral cavity

 

D38.0

Neoplasm of uncertain behavior of larynx

Procedure and diagnosis codes on Medical Policy documents are included only as a general reference tool for each policy. They may not be all-inclusive. 

This medical policy was developed through consideration of peer-reviewed medical literature generally recognized by the relevant medical community, U.S. FDA approval status, nationally accepted standards of medical practice and accepted standards of medical practice in this community, Blue Cross and Blue Shield Association technology assessment program (TEC) and other non-affiliated technology evaluation centers, reference to federal regulations, other plan medical policies and accredited national guidelines.

"Current Procedural Terminology© American Medical Association.  All Rights Reserved" 

History From 2015 Forward     

06/21/2021 

Annual review, no change to policy intent. 

10/29/2020 

Interim review to add the statement: BlueCross BlueShield of South Carolina recognizes uses and indications of injectable oncology medications (including chemotherapy/systemic therapy, therapeutic radiopharmaceuticals, and selected supportive therapies) to be medically necessary if they are listed in the NCCN Drugs and Biologics Compendium with Categories of Evidence + Consensus of 1, 2A and 2B. Treatments listed with a Category of Evidence and Consensus of 3 are considered unproven and not medically necessary.

06/18/2020 

Annual review, no change to policy intent. 

06/01/2019 

Annual review, adding medical necessity criteria "Opdivo is indicated for the treatment of patients with metastatic small cell lung cancer with progression after platinum-based chemotherapy and at least one other line of therapy." No other changes made. 

06/11/2018 

Annual review, adding medical necessity criteria for FDA approved use in intermediate or poor risk , previously untreated advanced renal cell carcinoma in combination with ipilimumab. Also adding compendial uses: classical Hodgkin lymphoma, renal cell carcinoma, malignant pleural mesothelioma, NSCLC and small cell lung cancer. No other changes made. 

01/11/2018 

Interim Review. Updating policy verbiage to include additional medically necessary uses of Opdivo.

01/03/2018 

Interim review, updating coding. 

07/24/2017 

Interim review updating the medically necessary indications for use of Opdivo. No other changes made. 

05/01/2017 

Interim review to add updated medical necessity criteria related to Hodgkin lymphoma, squamous cell carcinoma of the head and neck and locally advanced or metastatic urothelial carcinoma. No other changes 

01/31/2017 

Removed language regarding adjuvant therapy 

01/25/2017 

Interim review adding details about the medical necessity for adjuvant melanoma treatment and the available program for coverage from the manufacturer. 

06/02/2016 

Annual review, no change to policy intent. 

05/10/2016 

Interim review to add the following medical necessity criteria: renal cell carcinoma 

06/08/2015

NEW POLICY 

 


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