Coverage Policies

Effective Date:

a)    This policy will apply to all services performed on or after the above revision date which will become the new effective date.

b)    For all services referred to in this policy that were performed before the revision date, contact customer service for the rules that would apply.

1.    Opdivo (Nivolumab) requires prior authorization.

2.    Opdivo is used to treat a number of different types of cancer.

Opdivo (Nivolumab) is considered medically necessary for patients with:

A.   Melanoma (must meet all):

1.    Diagnosis of unresectable, metastatic, or lymph node positive melanoma;

2.    Prescribed by or in consultation with an oncologist;

3.    Age ≥ 12 years;

4.    Request meets one of the following (a, b, or c):*

a.    If prescribed as monotherapy (unresectable or metastatic disease, or adjuvant treatment), dose does not exceed any of the following (i or ii):

i.      Adult and pediatric members weighing ≥ 40 kg: 240 mg every 2 weeks or 480 mg every 4 weeks;

ii.    Pediatric members weighing < 40 kg: 3 mg/kg every 2 weeks or 6 mg/kg every 4 weeks (see Appendix E for dose rounding guidelines);

b.    If prescribed in combination with Yervoy® (unresectable or metastatic disease), dose does not exceed any of the following (i or ii; see Appendix E for dose rounding guidelines):

i.      Adult and pediatric members weighing ≥ 40 kg: 1 mg/kg every 3 weeks for 4 doses, followed by 240 mg every 2 weeks or 480 mg every 4 weeks;

ii.    Pediatric members weighing < 40 kg: 1 mg/kg every 3 weeks for 4 doses, followed by 3 mg/kg every 2 weeks or 6 mg/kg every 4 weeks;

c.    Dose is supported by practice guidelines or peer-reviewed literature for the relevant off-label use (prescriber must submit supporting evidence).

*Prescribed regimen must be FDA-approved or recommended by NCCN  

Approval duration: 6 months

B.   Non-Small Cell Lung Cancer (must meet all):

1.    Diagnosis of resectable, recurrent, advanced, or metastatic NSCLC;

2.    Prescribed by or in consultation with an oncologist;

3.    Age ≥ 18 years;

4.    Member has not previously progressed on a PD-1/PD-L1 inhibitor (e.g., Keytruda®, Tecentriq®, Imfinzi®);

5.    For resectable NSCLC: Both of the following are met (a and b):

a.    Opdivo is prescribed as neoadjuvant treatment;

b.    Tumors ≥ 4 cm or node positive disease;

6.    For recurrent, advanced, or metastatic NSCLC: Opdivo is prescribed in one of the following ways (a, b, or c):

a.    For use as a single agent, and disease has progressed on or after systemic therapy;

b.    For use as a single agent or in combination with Yervoy for tumors positive for the Tumor Mutation Burden (TMB) biomarker;

c.    For use in combination with Yervoy, and both of the following (i and ii):

i.      Request meets one of the following (a, b, or c):

a)    Disease mutation status is unknown or negative for EGFR, ALK, ROS1, BRAF, MET exon 14 skipping, and RET, and member has not received prior systemic therapy for advanced disease;

b)    Disease mutation status is positive for EGFR, ALK, ROS1, BRAF, MET exon 14 skipping, RET, or NTRK gene fusion, and member has received mutation-specific treatment;

c)    Disease is positive for a RET rearrangement;

ii.    Request meets one of the following (a or b):

a)    Member has PD-L1 tumor expression of ≥ 1%;

b)    Opdivo is being used in combination with Yervoy ± a platinum-based regimen (see Appendix B);

*Prior authorization may be required for Yervoy

7.    Request meets one of the following (a, b, c, d, or e):*

a.    Monotherapy: Dose does not exceed 240 mg every 2 weeks or 480 mg every 4 weeks;

b.    In combination with Yervoy: Dose does not exceed 3 mg/kg every 2 weeks (see Appendix E for dose rounding guidelines);

c.    In combination with Yervoy and platinum-doublet chemotherapy: Dose does not exceed 360 mg every 3 weeks;

d.    In combination with platinum-doublet chemotherapy, both of the following are met (i and ii):

i.      Dose does not exceed 360 mg every 3 weeks;

ii.    Request does not exceed 3 cycles;

e.    Dose is supported by practice guidelines or peer-reviewed literature for the relevant off-label use (prescriber must submit supporting evidence).

*Prescribed regimen must be FDA-approved or recommended by NCCN  

Approval duration: 6 months (9 weeks for neoadjuvant NSCLC)

C.   Malignant Pleural Mesothelioma (must meet all):

1.    Diagnosis of unresectable malignant pleural mesothelioma;

2.    Prescribed by or in consultation with an oncologist;

3.    Age ≥ 18 years;

4.    Prescribed in one of the following ways (a or b):

a.    As first-line therapy in combination with Yervoy;

b.    If not administered first-line, as subsequent therapy in combination with Yervoy or as a single agent;

5.    Request meets one of the following (a or b):*

a.    Dose does not exceed 360 mg every 3 weeks;

b.    Dose is supported by practice guidelines or peer-reviewed literature for the relevant off-label use (prescriber must submit supporting evidence).

*Prescribed regimen must be FDA-approved or recommended by NCCN  

Approval duration: 6 months

D.   Renal Cell Carcinoma (must meet all):

1.    Diagnosis of RCC;

2.    Prescribed by or in consultation with an oncologist;

3.    Age ≥ 18 years;

4.    Request meets one of the following (a, b, or c):*

a.    Monotherapy or in combination with cabozantinib: Dose does not exceed 240 mg every 2 weeks or 480 mg every 4 weeks;

b.    In combination with Yervoy: Dose does not exceed 3 mg/kg every 3 weeks for 4 doses, followed by 240 mg every 2 weeks or 480 mg every 4 weeks (see Appendix E for dose rounding guidelines);

c.    Dose is supported by practice guidelines or peer-reviewed literature for the relevant off-label use (prescriber must submit supporting evidence).

*Prescribed regimen must be FDA-approved or recommended by NCCN  

Approval duration: 6 months

E.   Classical Hodgkin Lymphoma (must meet all):

1.    Diagnosis of relapsed, refractory or progressive cHL;

2.    Prescribed by or in consultation with an oncologist;

3.    Age ≥ 18 years;

4.    Prescribed as subsequent therapy;

5.    Request meets one of the following (a or b):*

a.    Dose does not exceed 240 mg every 2 weeks or 480 mg every 4 weeks;   

b.    Dose is supported by practice guidelines or peer-reviewed literature for the relevant off-label use (prescriber must submit supporting evidence).

*Prescribed regimen must be FDA-approved or recommended by NCCN  

Approval duration: 6 months

F.    Squamous Cell Carcinoma of the Head and Neck (must meet all):

1.    Diagnosis of SCCHN;

2.    Prescribed by or in consultation with an oncologist;

3.    Age ≥ 18 years;

4.    Prescribed as a single agent;

5.    Disease has progressed on or after a platinum-containing regimen (e.g., cisplatin, carboplatin);

6.    Request meets one of the following (a or b):*

a.    Dose does not exceed 240 mg every 2 weeks or 480 mg every 4 weeks;   

b.    Dose is supported by practice guidelines or peer-reviewed literature for the relevant off-label use (prescriber must submit supporting evidence).

*Prescribed regimen must be FDA-approved or recommended by NCCN  

Approval duration: 6 months

G.   Urothelial Carcinoma (must meet all):

1.    Diagnosis of UC;

2.    Prescribed by or in consultation with an oncologist;

3.    Age ≥ 18 years;

4.    One of the following (a, b, or c):

a.    Failure of a platinum-containing regimen (e.g., cisplatin, carboplatin), unless clinically significant adverse effects are experienced or all are contraindicated;

b.    Prescribed as adjuvant treatment and member is at high risk of recurrence after undergoing resection of UC;

c.    Member is at high risk of recurrence and did not previously receive a platinum-containing regimen;

5.    Request meets one of the following (a or b):*

a.    Dose does not exceed 240 mg every 2 weeks or 480 mg every 4 weeks;   

b.    Dose is supported by practice guidelines or peer-reviewed literature for the relevant off-label use (prescriber must submit supporting evidence).

*Prescribed regimen must be FDA-approved or recommended by NCCN  

Approval duration: 6 months

H.   Colorectal Cancer (must meet all):

1.    Diagnosis of unresectable or metastatic CRC;

2.    Tumor is characterized as MSI-H or dMMR;

3.    Prescribed by or in consultation with an oncologist;

4.    Age ≥ 12 years;

5.    Dose does not exceed one of the following (a, b, or c):*

a.    Monotherapy: 240 mg every 2 weeks;

b.    In combination with Yervoy: 3 mg/kg every 3 weeks for 4 doses, then 240 mg every 2 weeks or 480 mg every 4 weeks (see Appendix E for dose rounding guidelines);

c.    Dose is supported by practice guidelines or peer-reviewed literature for the relevant off-label use (prescriber must submit supporting evidence).

*Prescribed regimen must be FDA-approved or recommended by NCCN  

Approval duration: 6 months

I.     Hepatocellular Carcinoma (must meet all):

1.    Diagnosis of HCC;

2.    Prescribed by or in consultation with an oncologist;

3.    Age ≥ 18 years;

4.    Member has had disease progression following treatment with Nexavar®, Lenvima®, Tecentriq® + bevacizumab (Mvasi® and Zirabev™ are preferred), or Imfinzi®;
*Prior authorization may be required for Nexavar, Lenvima, Tecentriq, bevacizumab, and Imfinzi.

5.    Prescribed in combination with Yervoy;

6.    Documentation of Child-Pugh Class A status;

7.    Dose does not exceed one of the following (a or b):*

a.    In combination with Yervoy: 1 mg/kg every 3 weeks for 4 doses, then 240 mg every 2 weeks or 480 mg every 4 weeks (see Appendix E for dose rounding guidelines);

b.    Dose is supported by practice guidelines or peer-reviewed literature for the relevant off-label use (prescriber must submit supporting evidence).

*Prescribed regimen must be FDA-approved or recommended by NCCN  

Approval duration: 6 months

J.    Esophageal Cancer (must meet all):

1.    Diagnosis of one of the following (a or b):

a.    Completely resected esophageal cancer or gastroesophageal junction (esophagogastric junction; EGJ) cancer;

b.    Unresectable advanced, recurrent, or metastatic ESCC;

2.    Prescribed by or in consultation with an oncologist;

3.    Age ≥ 18 years;

4.    For completely resected esophageal cancer or EGJ cancer, member meets both of the following (a and b):

a.    Member has residual pathologic disease;

b.    Member has previously received CRT;

5.    For ESCC, one of the following (a or b):

a.    For unresectable advanced or metastatic disease: Prescribed in combination with Yervoy or with fluoropyrimidine- and platinum-containing chemotherapy;

b.    For unresectable advanced, recurrent, or metastatic disease: Member has had previous treatment with a fluoropyrimidine-based (e.g., 5-fluorouracil, capecitabine) and platinum-based (e.g., carboplatin, cisplatin, oxaliplatin) chemotherapy;

6.    Request meets one of the following (a, b, or c):*

a.    ESCC in combination with Yervoy: Dose does not exceed 3 mg/kg every 2 weeks or 360 mg every 3 weeks;

b.    Other indications: Dose does not exceed 240 mg every 2 weeks or 480 mg every 4 weeks;

c.    Dose is supported by practice guidelines or peer-reviewed literature for the relevant off-label use (prescriber must submit supporting evidence).

*Prescribed regimen must be FDA-approved or recommended by NCCN  

Approval duration: 6 months

K.   Gastric and Esophageal Adenocarcinomas (must meet all):

1.    Diagnosis of gastric cancer, EGJ cancer, or esophageal adenocarcinoma;

2.    Member meets one of the following (a or b):

a.    Disease is advanced, recurrent, or metastatic;

b.    For EGJ cancer or esophageal adenocarcinoma: member meets one of the following (i or ii):

i.      Member is post-operative following chemoradiation;

ii.    Disease is advanced, recurrent, or metastatic;

3.    Prescribed by or in consultation with an oncologist;

4.    Age ≥ 18 years;

5.    For advanced, recurrent, or metastatic disease: both of the following are met (a and b):

a.    Prescribed in combination with a fluoropyrimidine- (e.g., 5-fluorouracil, capecitabine) and platinum-containing (e.g., carboplatin, cisplatin, oxaliplatin) chemotherapy;

b.    Disease is HER2-negative;

6.    Request meets one of the following (a or b):*

a.    Dose does not exceed 240 mg every 2 weeks or 360 mg every 3 weeks;

b.    Dose is supported by practice guidelines or peer-reviewed literature for the relevant off-label use (prescriber must submit supporting evidence).

*Prescribed regimen must be FDA-approved or recommended by NCCN  

Approval duration: 6 months

A.   Off-label NCCN Compendium Recommended Indications (must meet all):

7.    Diagnosis of one of the following (a-o):

a.    Squamous cell anal carcinoma that is metastatic;

b.    Merkel cell carcinoma;

c.    Gestational trophoblastic neoplasia;

d.    Uveal melanoma that is metastatic;

e.    Small bowel adenocarcinoma that is advanced or metastatic;

f.     Extranodal NK/T-cell lymphoma, nasal type, that is relapsed or refractory;

g.    Pediatric Hodgkin lymphoma, as subsequent therapy;

h.    Vulvar cancer - HPV-related advanced, recurrent, or metastatic disease, as second-line treatment;

i.      Cervical cancer;

j.      Endometrial carcinoma that is recurrent or metastatic;

k.    Small cell lung cancer, as subsequent therapy;

l.      Bone cancer (e.g., Ewing Sarcoma, chordoma, osteosarcoma, chondrosarcoma);

m.  Central nervous system (CNS) cancer (e.g., brain metastases);

n.    Pediatric primary mediastinal large B-cell lymphoma;

o.    Pediatric diffuse high-grade gliomas;

8.    Prescribed by or in consultation with an oncologist;

9.    For anal carcinoma: prescribed as second line or subsequent therapy (examples of prior therapy include 5-FU/cisplatin, carboplatin/paclitaxel, FOLFOX, FOLFCIS);

10. For gestational trophoblastic neoplasia: prescribed as a single agent for multi-agent chemotherapy-resistant disease (see Appendix B) in one of the following settings (a or b):

a.    Recurrent or progressive intermediate trophoblastic tumor following treatment with a platinum-containing regimen (e.g., cisplatin, carboplatin);

b.    High-risk disease (see Appendix D);

11. For pediatric primary mediastinal large B-cell lymphoma: prescribed as one of the following (a or b):

a.    As a single agent as second line therapy after failure of induction therapy/initial treatment (see appendix B);

b.    Combination with brentuximab vedotin as consolidation/additional therapy;

12. For pediatric diffuse high-grade gliomas: prescribed as a single agent for adjuvant therapy or for recurrent/progressive disease;

13. For uveal melanoma, bone cancer, CNS cancer: prescribed as a single agent or in combination with Yervoy;

*Prior authorization may be required for Yervoy.

14. For cervical cancer: prescribed as second line or subsequent therapy for PD-L1 tumor expression of ≥ 1%;

15. Dose is within FDA maximum limit for any FDA-approved indication or is supported by practice guidelines or peer-reviewed literature for the relevant off-label use (prescriber must submit supporting evidence).*

*Prescribed regimen must be FDA-approved or recommended by NCCN  

Approval duration: 6 months

Codes Used in this BI:

J9299 – Injection, Nivolumab, 1mg (Opdivo) effective 1/01/2016

i)     Opdivo Prescribing Information. Princeton, NJ: Bristol-Myers Squibb; February 2023. Available at https://www.opdivo.com/. Accessed March 16, 2023.

ii)    National Comprehensive Cancer Network Drugs and Biologics Compendium. Available at http://www.nccn.org. Accessed April 13, 2023.

iii)   National Comprehensive Cancer Network. Non-Small Cell Lung Cancer Version 5.2022. Available at: https://www.nccn.org/professionals/physician_gls/pdf/nscl.pdf. Accessed November 4, 2022.

iv)   National Comprehensive Cancer Network. Kidney Cancer, Version 3.2023. Available at: https://www.nccn.org/professionals/physician_gls/pdf/kidney.pdf. Accessed November 04, 2022.

v)    Hellman MD, Paz-Ares L, Bernabe Caro R, et al. Nivolumab plus ipilimumab in advanced non-small-cell lung cancer. N Engl J Med. 2019 November; 381(21):2020-2031.

vi)   National Comprehensive Cancer Network. Bladder Cancer, Version 2.2022. Available at: https://www.nccn.org/professionals/physician_gls/pdf/bladder.pdf. Accessed November 04, 2022.

vii)  National Comprehensive Cancer Network. Hepatobiliary Cancers, Version 3.2022. Available at: https://www.nccn.org/professionals/physician_gls/pdf/hepatobiliary.pdf. Accessed November 4, 2022.

viii)National Comprehensive Cancer Network. Esophageal and Esophagogastric Junction Cancers, Version 4.2022. Available at: https://www.nccn.org/professionals/physician_gls/pdf/esophageal.pdf. Accessed November 4, 2022.

ix)   National Comprehensive Cancer Network. Pediatric Central Nervous System Cancers, Version 2.2023. Available at: https://www.nccn.org/professionals/physician_gls/pdf/ped_cns.pdf. Accessed November 4, 2022.

x)    National Comprehensive Cancer Network. Central Nervous System Cancers, Version 2.2022. Available at: https://www.nccn.org/professionals/physician_gls/pdf/cns.pdf. Accessed November 4, 2022.

xi)   National Comprehensive Cancer Network. Pediatric Aggressive Mature B-Cell Lymphomas, Version 3.2022. Available at: https://www.nccn.org/professionals/physician_gls/pdf/ped_b-cell.pdf. Accessed November 4, 2022.

xii)  National Comprehensive Cancer Network. Bone Cancer, Version 2.2023. Available at: https://www.nccn.org/professionals/physician_gls/pdf/bone.pdf. Accessed November 4, 2022.

xiii)National Comprehensive Cancer Network. Melanoma: Cutaneous, Version 2.2023. Available at: https://www.nccn.org/professionals/physician_gls/pdf/cutaneous_melanoma.pdf. Accessed April 13, 2023.

Addendum:

1.    Effective 01/01/2017: Updated approved diagnoses of head and neck cancer, classical Hodgkin Lymphoma, and small cell lung cancer.

2.    Effective  05/01/2017: Updated approved diagnosis of bladder cancer

3.    Effective 11/01/2017: Updated approved diagnosis of hepatocellular cancer.

4.    Effective 03/01/2019: Updated criteria for hepatocellular cancer by removing requirement for progression on, or intolerance to Nexavar per NCCN.

5.    Effective 04/01/2019: Updated to include reference to using Opdivo as first-line treatment in advanced RCC in combination with Yervoy. Updated criteria for melanoma.

6.    Effective 12/01/2021: Updated to include coverage for malignant pleural mesothelioma, esophageal cancer, gastric cancer, gastroesophageal junction cancer, and esophageal adenocarcinoma.

7.    Effective 08/01/2023: Updated policy completely to incorporate all FDA-approved indications.