BlueCross BlueShield of Tennessee Medical Policy Manual

Nivolumab (Opdivo®) (Intravenous)

NDC CODE(S)

00003-3772-XX OPDIVO 10MG/ML Solution (B-M SQUIBB U.S. (PRIMARY CARE))

00003-3774-XX OPDIVO 100MG/10ML Solution (B-M SQUIBB U.S. (PRIMARY CARE))

00003-3734-XX OPDIVO 240MG/24ML Solution (B-M SQUIBB U.S. (PRIMARY CARE))

DESCRIPTION

Nivolumab is a human monoclonal antibody classified as an IgG4 kappa immunoglobulin.  It blocks the interaction with PD-1, programmed death receptor-1, and its ligands PD-L1 and PD-L2.  When the PD-1 receptor found on T-cells binds with its ligands, T-cell proliferation and cytokine production is inhibited.  Some tumors cause increased production of PD-1 ligands and can contribute to the inhibition of active T-cell immune surveillance of tumors. Nivolumab releases pathway-mediated inhibition of the immune response, including the anti-tumor immune response, which results in decreased tumor growth.   

POLICY 

MEDICAL APPROPRIATENESS

INITIAL APPROVAL CRITERIA

LENGTH OF AUTHORIZATION

Universal Criteria

Cutaneous Melanoma

*Metastatic disease includes stage III clinical satellite/in transit metastases or local satellite/in-transit recurrence in patients with limited resectable and unresectable disease, unresectable nodal recurrence, and disseminated (unresectable) distant metastatic disease

Uveal Melanoma

Hepatocellular Carcinoma (HCC)

Non-Small Cell Lung Cancer (NSCLC)

** Note: If there is insufficient tissue to allow testing for all of the EGFR, ALK, ROS1, BRAF, NTRK1/2/3, MET, and RET, repeat biopsy and/or plasma testing should be done. If these are not feasible, treatment is guided by available results and, if unknown, these patients are treated as though they do not have driver oncogenes.

Renal Cell Carcinoma (RCC)

Adult Classical Hodgkin Lymphoma (cHL)

Pediatric Classical Hodgkin Lymphoma (cHL)

* Pediatric Hodgkin Lymphoma may be applicable to adolescent and young adult (AYA) patients up to the age of 39 years.     

Squamous Cell Carcinoma of the Head and Neck (SCCHN)

Urothelial Carcinoma (Bladder Cancer)

*Note:

If platinum treatment occurred greater than 12 months ago, the patient should be re-treated with platinum-based therapy if the patient is still platinum eligible (see below for cisplatin- or carboplatin-ineligible comorbidities).

·         Cisplatin-ineligible comorbidities may include the following: GFR < 60 mL/min, PS ≥ 2, hearing loss of ≥ 25 decibels (dB) at two contiguous frequencies, or grades ≥ 2 peripheral neuropathy. Carboplatin may be substituted for cisplatin particularly in those patients with a GFR <60 mL/min or a PS of 2.

·         Carboplatin-ineligible comorbidities may include the following: GFR < 30 mL/min, PS ≥ 3, grade ≥ 3 peripheral neuropathy, or NYHA class ≥ 3, etc.

Colorectal Cancer (CRC)

* Single agent nivolumab should be used in patients who are not candidates for intensive therapy

Merkel Cell Carcinoma

Central Nervous System (CNS) Cancer

Anal Carcinoma

Gestational Trophoblastic Neoplasia

Malignant Pleural Mesothelioma

Small Bowel Adenocarcinoma

Extranodal NK/ T-Cell Lymphoma

Esophageal and Esophagogastric Junction Cancers

Gastric Cancer

Endometrial Carcinoma (Uterine Neoplasms)

Vulvar Cancer (Squamous Cell Carcinoma)

If confirmed using an immunotherapy assay-http://www.fda.gov/CompanionDiagnostics

 

****Genomic Aberration/Mutational Driver Targeted Therapies

(NOTE: not all inclusive, refer to guidelines for appropriate use)

Sensitizing EGFR mutation-positive tumors

  • Afatinib

  • Dacomitinib

  • Erlotinib

  • Gefitinib

  • Osimertinib

ALK rearrangement-positive tumors

  • Alectinib

  • Brigatinib

  • Ceritinib

  • Crizotinib

  • Lorlatinib 

ROS1 rearrangement-positive tumors

  • Ceritinib

  • Crizotinib

  • Entrectinib

BRAF V600E-mutation positive tumors

  • Dabrafenib +Trametinib

  • Vemurafenib

 NTRK Gene Fusion positive tumors

  • Larotrectinib

  • Entrectinib

PD-1/PD-L1 expression-positive tumors (≥1%)

  • Pembrolizumab

  • Atezolizumab

  • Nivolumab ± ipilimumab

MET Exon-14 skipping mutations

  • Capmatinib

  • Crizotinib

RET rearrangement-positive tumors

  • Cabozantinib

  • Selpercatinib

  • Vandetanib

RENEWAL CRITERIA

Cutaneous Melanoma (adjuvant therapy)

NSCLC (in combination with ipilimumab or in combination with ipilimumab and two (2) cycles of platinum-doublet chemotherapy)

MPM (combination with ipilimumab)

Vulvar Cancer

Renal Cell Carcinoma (in combination with cabozantinib)

Esophageal and Esophagogastric Junction Adenocarcinoma and Squamous Cell Carcinoma (single agent postoperative therapy)

cHL (in combination with brentuximab vedotin)

Cutaneous Melanoma Re-induction

DOSAGE/ADMINISTRATION

Max Units (per dose and over time) [HCPCS Unit]:

INDICATION

DOSE

Merkel Cell

Administer 240 mg intravenously every 2 weeks or 3 mg/kg intravenously every 2 weeks until disease progression or unacceptable toxicity

Anal Cancer

Administer 240 mg intravenously every 2 weeks, 480 mg intravenously every 4 weeks, or 3 mg/kg intravenously every 2 weeks until disease progression or unacceptable toxicity

Cutaneous Melanoma

Single agent (excluding adjuvant therapy):

• Administer 240 mg intravenously every 2 weeks or 480 mg intravenously every 4 weeks until disease progression or unacceptable toxicity

In combination with ipilimumab (excluding adjuvant therapy):

• Administer 1 mg/kg intravenously, with ipilimumab on the same day, every 3 weeks for 4 doses, then follow with single agent regimen

Adjuvant treatment:

• Administer 240 mg intravenously every 2 weeks or 480 mg intravenously every 4 weeks until disease recurrence or unacceptable toxicity for up to 1 year

Uveal Melanoma

Single agent:

• Administer up to 10 mg/kg intravenously every 2 weeks until disease progression or unacceptable toxicity

In combination with ipilimumab:

• Administer 1 mg/kg intravenously, with ipilimumab on the same day, every 3 weeks for 4 doses, then 3 mg/kg intravenously every 2 weeks until disease progression or unacceptable toxicity

NSCLC

Single agent:

• Administer 240 mg intravenously every 2 weeks OR 480 mg intravenously every 4 weeks until disease progression or unacceptable toxicity

In combination with ipilimumab:

• Administer 3 mg/kg intravenously every 2 weeks, with ipilimumab 1 mg/kg every 6 weeks, until disease progression or unacceptable toxicity for up to 2 years

In combination with ipilimumab and platinum-doublet chemotherapy for metastatic or recurrent disease:

• Administer 360 mg intravenously every 3 weeks, with ipilimumab 1 mg/kg every 6 weeks and histology-based platinum-doublet chemotherapy every 3 weeks for 2 cycles,  then continue 360 mg every 3 weeks until disease progression or unacceptable toxicity for up to 2 years

SCCHN, Urothelial Carcinoma, & Gestational Trophoblastic Neoplasia (GTN)

Administer 240 mg intravenously every 2 weeks or 480 mg intravenously every 4 weeks until disease progression or unacceptable toxicity

cHL

Single-agent:

• Administer 240 mg intravenously every 2 weeks or 480 mg intravenously every 4 weeks until disease progression or unacceptable toxicity

In combination with brentuximab vedotin

• Administer 3 mg/kg intravenously every 3 weeks for up to 12 weeks (4 cycles) (NOTE: brentuximab vedotin is given on day 1 and nivolumab is given on day 8 of cycle 1 and both are given on day 1 of all subsequent cycles)

MSI-H/dMMR CRC

Adult patients and for pediatric patients ≥ 12 years and ≥ 40 kg

As a single agent: Administer 240 mg intravenously every 2 weeks or 480 mg intravenously every 4 weeks until disease progression or unacceptable toxicity

• In combination with ipilimumab: Administer 3 mg/kg intravenously, with ipilimumab 1 mg/kg on the same day, every 3 weeks for 4 doses, then follow with the single agent regimen

Pediatric patients ≥ 12 years and < 40 kg

• As a single agent: Administer 3 mg/kg intravenously every 2 weeks until disease progression or unacceptable toxicity

• In combination with ipilimumab: Administer 3 mg/kg intravenously, with ipilimumab 1 mg/kg on the same day, every 3 weeks for 4 doses, then follow with the single agent regimen

Renal Cell Carcinoma (RCC)

Single-agent:

• Administer 240 mg intravenously every 2 weeks or 480 mg intravenously every 4 weeks until disease progression or unacceptable toxicity

In combination with ipilimumab:

• Administer 3 mg/kg intravenously, with ipilimumab on the same day, every 3 weeks for 4 doses, then follow with single-agent regimen

In combination with cabozantinib (Cabometyx):

• Administer 240 mg intravenously every 2 weeks or 480 mg intravenously every 4 weeks until disease progression or unacceptable toxicity for up to 2 years

Hepatocellular Carcinoma (HCC)

Single-agent:

• Administer 240 mg intravenously every 2 weeks or 480 mg intravenously every 4 weeks until disease progression or unacceptable toxicity

In combination with ipilimumab:

• Administer 1 mg/kg intravenously, with ipilimumab on the same day, every 3 weeks for 4 doses, then follow with single-agent regimen

Malignant Pleural Mesothelioma (MPM)

Single agent:

• Administer 3 mg/kg intravenously every 2 weeks until disease progression or unacceptable toxicity

In combination with ipilimumab:

• Subsequent Therapy

− Administer 3 mg/kg intravenously every 2 weeks, with ipilimumab 1 mg/kg every 6 weeks, until disease progression or unacceptable toxicity for up to 2 years OR

− Administer 240 mg intravenously every 2 weeks, with ipilimumab 1 mg/kg every 6 weeks (for a total of 4 ipilimumab doses); treatment with nivolumab is continued for up to 2 years or until disease progression or unacceptable toxicity

• Initial Therapy

− Administer 360 mg intravenously every 3 weeks, with ipilimumab 1 mg/kg every 6 weeks; until disease progression or unacceptable toxicity for up to 2 years

CNS Metastases from Melanoma

Single agent:

• Administer 3 mg/kg intravenously every 2 weeks until disease progression or unacceptable toxicity

In combination with ipilimumab:

• Administer 1 mg/kg intravenously, with ipilimumab on the same day, every 3 weeks for 4 doses, then 3 mg/kg intravenously every 2 weeks until disease progression or unacceptable toxicity

CNS Metastases from NSCLC

Administer 3 mg/kg intravenously every 2 weeks until disease progression or unacceptable toxicity

Small Bowel Adenocarcinoma

Single agent:

• Administer 3 mg/kg intravenously every 2 weeks, or 240 mg intravenously every 2 weeks, or 480 mg intravenously every 4 weeks until disease progression or unacceptable toxicity

In combination with ipilimumab:

• Administer 3 mg/kg intravenously, with ipilimumab on the same day, every 3 weeks for 4 doses, then 3 mg/kg or 240 mg intravenously every 2 weeks until disease progression or unacceptable toxicity

Esophageal and Esophagogastric Junction Cancer

Esophageal Squamous Cell Carcinoma:

• Administer 240 mg intravenously every 2 weeks or 480 mg intravenously every 4 weeks until disease progression or unacceptable toxicity

Single agent for postoperative therapy:

• Administer 240 mg intravenously every 2 weeks for 16 weeks followed by 480 mg intravenously every 4 weeks for up to 1 year

In combination with oxaliplatin and either fluorouracil or capecitabine:

• Administer 360 mg intravenously every 3 weeks or 240 mg intravenously every 2 weeks until disease progression or unacceptable toxicity

Gastric Cancer

In combination with oxaliplatin and either fluorouracil or capecitabine:

Administer 360 mg intravenously every 3 weeks or 240 mg intravenously every 2 weeks until disease progression or unacceptable toxicity

Extranodal NK/ T-Cell Lymphoma

Administer 40 mg intravenously every 2 weeks until disease progression or unacceptable toxicity

Endometrial Carcinoma

Administer 3 mg/kg intravenously every 2 weeks for 8 doses and then 480 mg intravenously every 4 weeks until disease progression or unacceptable toxicity

Vulvar Cancer

Administer 240 mg intravenously every 2 weeks until disease progression or unacceptable toxicity for up to 2 years

Dosing should be calculated using actual body weight and not flat dosing (as applicable) based on the following:

Weight ≥ 74 kg:

·            Standard dose 480 mg IV every 4 weeksWeight is 67 kg to 73 kg:

·            Use 440 mg IV every 4 weeks Weight is ≤ 66kg:

·            Use 400 mg IV every 4 weeks

-OR-

Weight > 67 kg:

·            Standard dose 240 mg IV every 2 weeksWeight is 53 kg to 67 kg:

·            Use 200 mg IV every 2 weeks Weight is < 53kg:

·            Use 160 mg IV every 2 weeks

Note: This information is not meant to replace clinical decision making when initiating or modifying medication therapy and should only be used as a guide. Patient-specific variables should be taken into account.

LENGTH OF AUTHORIZATION

Coverage will be provided for six months and may be renewed (unless otherwise specified).

DOSAGE LIMITS

Max Units (per dose and over time) [HCPCS Unit]:

DIAGNOSIS

BILLABLE UNITS

PER UNIT TIME (days)

Merkel Cell & Anal Carcinoma

340 BU

14 days

Melanoma & HCC ( both in combination with ipilimumab)

Initial: 140 BU

21 days x 4 doses

Followed by:480 BU

28 days

Esophageal and Esophagogastric Junction Cancer (single agent postoperative therapy)

Initial: 240 BU

14 days x 8 doses

Followed by: 480 BU

28 days

Melanoma/HCC/NSCLC/cHL (as a single agent) RCC (as a single agent & in combination with cabozantinib), SCCHN, MSI-H/dMMR CRC (as a single agent), Gestational Trophoblastic Tumor, Esophageal Squamous Cell Carcinoma & Urothelial Carcinoma

480 BU

28 days

Metastatic NSCLC with PD-L1 expressing tumors (in combination with ipilimumab)

340 BU

14 days

Metastatic or recurrent NSCLC (in combination with ipilimumab and platinum-doublet chemotherapy), Esophageal and Esophagogastric Junction Cancer (in combination with oxaliplatin and either fluorouracil or capecitabine), Gastric Cancer

380 BU

21 days

Vulvar Cancer 

240 BU

14 days

cHL (in combination with brentuximab vedotin)

340 BU

21 days x 4 doses

MSI-H/dMMR CRC (in combination with ipilimumab)

Initial: 340 BU

21 days x 4 doses

Followed by: 480 BU

28 days

Small Bowel Adenocarcinoma & CNS Metastases from NSCLC (both as single agents)

340 BU

14 days

Small Bowel Adenocarcinoma (in combination with ipilimumab)

Initial: 340 BU

21 days x 4 doses

Followed by: 340 BU

14 days

RCC (in combination with ipilimumab)

Initial: 340 BU

21 days x 4 doses

Followed by:480 BU

28 days

MPM (as a single agent or in combination with ipilimumab)

340 BU

14 days

CNS Metastases from Melanoma & Uveal Melanoma (both in combination with ipilimumab)

Initial: 140 BU

21 days x 4 doses

Followed by: 340 BU

14 days

CNS Metastases from Melanoma (as a single agent)

340BU

14 days

Uveal Melanoma (As a single agent)

1140 BU

14 days

Extranodal NK/T-cell Lymphoma

40 BU

14 days

Endometrial Carcinoma

Initial: 340 BU

14 days x 8 doses

Followed by: 480 BU

28 days

APPLICABLE TENNESSEE STATE MANDATE REQUIREMENTS

BlueCross BlueShield of Tennessee’s Medical Policy complies with Tennessee Code Annotated Section 56-7-2352 regarding coverage of off-label indications of Food and Drug Administration (FDA) approved drugs when the off-label use is recognized in one of the statutorily recognized standard reference compendia or in the published peer-reviewed medical literature.

IMPORTANT REMINDER

We develop Medical Policies to provide guidance to Members and Providers.  This Medical Policy relates only to the services or supplies described in it.  The existence of a Medical Policy is not an authorization, certification, explanation of benefits or a contract for the service (or supply) that is referenced in the Medical Policy.  For a determination of the benefits that a Member is entitled to receive under his or her health plan, the Member's health plan must be reviewed.  If there is a conflict between the Medical Policy and a health plan, the express terms of the health plan will govern.

ADDITIONAL INFORMATION

For appropriate chemotherapy regimens, dosage information, contraindications, precautions, warnings, and monitoring information, please refer to one of the standard reference compendia (e.g., the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) published by the National Comprehensive Cancer Network®, Drugdex Evaluations of Micromedex Solutions at Truven Health, or The American Hospital Formulary Service Drug Information).

SOURCES 

1.     Opdivo [package insert]. Princeton, NJ; Bristol-Myers Squibb Company; December 2021. Accessed January 2021.

2.     Referenced with permission from the NCCN Drugs & Biologics Compendium (NCCN Compendium®) nivolumab. National Comprehensive Cancer Network, 2020. The NCCN Compendium® is a derivative work of the NCCN Guidelines®. NATIONAL COMPREHENSIVE CANCER NETWORK®, NCCN®, and NCCN GUIDELINES® are trademarks owned by the National Comprehensive Cancer Network, Inc. To view the most recent and complete version of the Compendium, go online to NCCN.org. Accessed January 2021.

3.     Scherpereel A, Mazieres J, Greillier L, et al. Second- or third-line nivolumab (Nivo) versus nivo plus ipilimumab (Ipi) in malignant pleural mesothelioma (MPM) patients: Results of the IFCT-1501 MAPS2 randomized phase II trial. [Abstract]. J Clin Oncol 2017;35: Abstract LBA 8507.

4.     Walocko FM, Scheier BY, Harms PW, et al. Metastatic Merkel cell carcinoma response to nivolumab. J Immunother Cancer. 2016 Nov 15;4:79.

5.     Tawbi HA-H, Forsyth PAJ, Algazi AP, et al. Efficacy and safety of nivolumab (NIVO) plus ipilimumab (IPI) in patients with melanoma (MEL) metastatic to the brain: Results of the phase II study CheckMate 204. J Clin Oncol 2017;35(15_suppl):abstr 9507.

6.     Morris VK, Salem ME, Nimeiri H, et al. Nivolumab for previously treated unresectable metastatic anal cancer (NCI9673): a multicentre, single-arm, phase 2 study. Lancet Oncol. 2017 Apr;18(4):446-453. doi: 10.1016/S1470-2045(17)30104-3. Epub 2017 Feb 18.

7.     Zhao X, Ivaturi V, Gopalakrishnan M, et al. Abstract CT 101: A model-based exposure-response (E-R) assessment of a nivolumab (NIVO) 4-weekly (Q4W) dosing schedule across multiple tumor types. Cancer Res July 1 2017 (77) (13 Supplement) CT101; DOI: 10.1158/1538-7445.AM2017-CT101.

8.     Zhao X, Suryawanshi M, Hruska M, et al. Assessment of nivolumab benefit-risk profile of a 240 mg flat dose relative to a 3 mg/kg dosing regimen in patients with advanced tumors. Ann Oncol2017; 28:2002-2008.

9.     Feng Y, Xiaoning W, Bajaj G, et al. Nivolumab exposure-response analyses of efficacy and safety in previously treated squamous or nonsquamous non-small cell lung cancer. ClinCa Res 2017;23(18): 5394-5405.

10.  Gupta S, Sonpavde G, Grivas P, et al. Defining “platinum-ineligible” patients with metastatic urothelial cancer (mUC). J Clin Oncol. 2019 Mar 1;37(7_suppl):451.

11.  Hellmann MD, Ciuleanu TE, Pluzanski A, et al. Nivolumab plus ipilimumab in lung cancer with a high tumor mutational burden. N Engl J Med 2018; 378:2093-2104.

12.  Fahrenbruch R, Kintzel P, Bott AM, et al. Dose Rounding of Biologic and Cytotoxic Anticancer Agents: A Position Statement of the Hematology/Oncology Pharmacy Association. J Oncol Pract. 2018 Mar;14(3):e130-e136.

13.  Hematology/Oncology Pharmacy Association (2019). Intravenous Cancer Drug Waste Issue Brief. Retrieved from http://www.hoparx.org/images/hopa/advocacy/Issue-Briefs/Drug_Waste_2019.pdf

14.  Bach PB, Conti RM, Muller RJ, et al. Overspending driven by oversized single dose vials of cancer drugs. BMJ. 2016 Feb 29;352:i788.

15.  Weber JS, D'Angelo SP, Minor D, et al. Nivolumab versus chemotherapy in patients with advanced melanoma who progressed after anti-CTLA-4 treatment (CheckMate 037): a randomised, controlled, open-label, phase 3 trial. Lancet Oncol. 2015 Apr;16(4):375-84. doi: 10.1016/S1470-2045(15)70076-8. Epub 2015 Mar 18.

16.  Robert C, Long GV, Brady B, et al. Nivolumab in previously untreated melanoma without BRAF mutation. N Engl J Med. 2015 Jan 22;372(4):320-30. doi: 10.1056/NEJMoa1412082. Epub 2014 Nov 16.

17.  Larkin J, Chiarion-Sileni V, Gonzalez R, et al. Combined Nivolumab and Ipilimumab or Monotherapy in Untreated Melanoma. N Engl J Med. 2015 Jul 2;373(1):23-34. doi: 10.1056/NEJMoa1504030. Epub 2015 May 31.

18.  Weber J, Mandala M, Del Vecchio M, et al. Adjuvant Nivolumab versus Ipilimumab in Resected Stage III or IV Melanoma. N Engl J Med. 2017 Nov 9;377(19):1824-1835. doi: 10.1056/NEJMoa1709030. Epub 2017 Sep 10.

19.  Algazi AP, Tsai KK, Shoushtari AN, et al. Clinical outcomes in metastatic uveal melanoma treated with PD-1 and PD-L1 antibodies. Cancer. 2016 Nov 15;122(21):3344-3353. doi: 10.1002/cncr.30258. Epub 2016 Aug 17.

20.  Piulats JM, Cruz-Merino LDL, Garcia MTC, et al. Phase II multicenter, single arm, open label study of nivolumab in combination with ipilimumab in untreated patients with metastatic uveal melanoma (GEM1402.NCT02626962). J Clin Oncol 2017; 35 Abstr 9533.

21.  El-Khoueiry AB, Sangro B, Yau T, et al. Nivolumab in patients with advanced hepatocellular carcinoma (CheckMate 040): an open-label, non-comparative, phase 1/2 dose escalation and expansion trial. Lancet. 2017 Jun 24;389(10088):2492-2502. doi: 10.1016/S0140-6736(17)31046-2. Epub 2017 Apr 20.

22.  Brahmer J, Reckamp KL, Baas P, et al. Nivolumab versus Docetaxel in Advanced Squamous-Cell Non-Small-Cell Lung Cancer. N Engl J Med. 2015 Jul 9;373(2):123-35. doi: 10.1056/NEJMoa1504627. Epub 2015 May 31.

23.  Borghaei H, Paz-Ares L, Horn L, et al. Nivolumab versus Docetaxel in Advanced Nonsquamous Non-Small-Cell Lung Cancer. N Engl J Med. 2015 Oct 22;373(17):1627-39. doi: 10.1056/NEJMoa1507643. Epub 2015 Sep 27.

24.  Antonia SJ, López-Martin JA, Bendell J, et al. Nivolumab alone and nivolumab plus ipilimumab in recurrent small-cell lung cancer (CheckMate 032): a multicentre, open-label, phase 1/2 trial. Lancet Oncol. 2016 Jul;17(7):883-895. doi: 10.1016/S1470-2045(16)30098-5. Epub 2016 Jun 4.

25.  Motzer RJ, Escudier B, McDermott DF, et al. Nivolumab versus Everolimus in Advanced Renal-Cell Carcinoma. N Engl J Med. 2015 Nov 5;373(19):1803-13. doi: 10.1056/NEJMoa1510665. Epub 2015 Sep 25.

26.  Motzer RJ, Tannir NM, McDermott DF, et al. Nivolumab plus Ipilimumab versus Sunitinib in Advanced Renal-Cell Carcinoma. N Engl J Med. 2018 Apr 5;378(14):1277-1290. doi: 10.1056/NEJMoa1712126. Epub 2018 Mar 21.

27.  Armand P, Engert A, Younes A, et al. Nivolumab for Relapsed/Refractory Classic Hodgkin Lymphoma After Failure of Autologous Hematopoietic Cell Transplantation: Extended Follow-Up of the Multicohort Single-Arm Phase II CheckMate 205 Trial. J Clin Oncol. 2018 May 10;36(14):1428-1439. doi: 10.1200/JCO.2017.76.0793. Epub 2018 Mar 27.

28.  Ansell SM, Lesokhin AM, Borrello I, et al. PD-1 blockade with nivolumab in relapsed or refractory Hodgkin's lymphoma. N Engl J Med. 2015 Jan 22;372(4):311-9. doi: 10.1056/NEJMoa1411087. Epub 2014 Dec 6.

29.  Ferris RL, Blumenschein G Jr, Fayette J, et al. Nivolumab for Recurrent Squamous-Cell Carcinoma of the Head and Neck. N Engl J Med. 2016 Nov 10;375(19):1856-1867. Epub 2016 Oct 8.

30.  Sharma P, Retz M, Siefker-Radtke A, et al. Nivolumab in metastatic urothelial carcinoma after platinum therapy (CheckMate 275): a multicentre, single-arm, phase 2 trial. Lancet Oncol. 2017 Mar;18(3):312-322. doi: 10.1016/S1470-2045(17)30065-7. Epub 2017 Jan 26.

31.  Overman MJ, McDermott R, Leach JL, et al. Nivolumab in patients with metastatic DNA mismatch repair-deficient or microsatellite instability-high colorectal cancer (CheckMate 142): an open-label, multicentre, phase 2 study. Lancet Oncol. 2017 Sep;18(9):1182-1191. doi: 10.1016/S1470-2045(17)30422-9. Epub 2017 Jul 19.

32.  Overman MJ, Lonardi S, Wong KYM, et al. Durable Clinical Benefit With Nivolumab Plus Ipilimumab in DNA Mismatch Repair-Deficient/Microsatellite Instability-High Metastatic Colorectal Cancer. J Clin Oncol. 2018 Mar 10;36(8):773-779. doi: 10.1200/JCO.2017.76.9901. Epub 2018 Jan 20.

33.  Topalian SL, Bhatia S, Hollebecque A, et al. Non-comparative, open-label, multiple cohort, phase 1/2 study to evaluate nivolumab (NIVO) in patients with virus-associated tumors (CheckMate 358): Efficacy and safety in Merkel cell carcinoma (MCC). DOI: 10.1158/1538-7445.AM2017-CT074 Published July 2017.

34.  Long GV, Atkinson V, Lo S, et al. Combination nivolumab and ipilimumab or nivolumab alone in melanoma brain metastases: a multicentre randomised phase 2 study. Lancet Oncol. 2018 May;19(5):672-681. doi: 10.1016/S1470-2045(18)30139-6. Epub 2018 Mar 27.

35.  Referenced with permission from the NCCN Drugs & Biologics Compendium (NCCN Compendium®) Anal Carcinoma. Version 2.2020. National Comprehensive Cancer Network, 2021. The NCCN Compendium® is a derivative work of the NCCN Guidelines®. NATIONAL COMPREHENSIVE CANCER NETWORK®, NCCN®, and NCCN GUIDELINES® are trademarks owned by the National Comprehensive Cancer Network, Inc. To view the most recent and complete version of the Compendium, go online to NCCN.org. Accessed January 2021.

36.  Referenced with permission from the NCCN Drugs & Biologics Compendium (NCCN Compendium®) Gestational Trophoblastic Neoplasia. Version 3.2020. National Comprehensive Cancer Network, 2021. The NCCN Compendium® is a derivative work of the NCCN Guidelines®. NATIONAL COMPREHENSIVE CANCER NETWORK®, NCCN®, and NCCN GUIDELINES® are trademarks owned by the National Comprehensive Cancer Network, Inc. To view the most recent and complete version of the Compendium, go online to NCCN.org. Accessed January 2021.

37.  Scherpereel A, Mazieres J, Greillier L, et al. Nivolumab or nivolumab plus ipilimumab in patients with relapsed malignant pleural mesothelioma (IFCT-1501 MAPS2): a multicentre, open-label, randomised, non-comparative, phase 2 trial. Lancet Oncol. 2019 Feb;20(2):239-253. doi: 10.1016/S1470-2045(18)30765-4. Epub 2019 Jan 16.

38.  Disselhorst MJ, Quispel-Janssen J, Lalezari F, et al. Ipilimumab and nivolumab in the treatment of recurrent malignant pleural mesothelioma (INITIATE): results of a prospective, single-arm, phase 2 trial. Lancet Respir Med. 2019 Mar;7(3):260-270. doi: 10.1016/S2213-2600(18)30420-X. Epub 2019 Jan 16.

39.  Referenced with permission from the NCCN Drugs & Biologics Compendium (NCCN Compendium®) Small Bowel Adenocarcinoma. Version 2.2020. National Comprehensive Cancer Network, 2021. The NCCN Compendium® is a derivative work of the NCCN Guidelines®. NATIONAL COMPREHENSIVE CANCER NETWORK®, NCCN®, and NCCN GUIDELINES® are trademarks owned by the National Comprehensive Cancer Network, Inc. To view the most recent and complete version of the Compendium, go online to NCCN.org. Accessed January 2021.

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ORIGINAL EFFECTIVE DATE:  2/5/2015

MOST RECENT REVIEW DATE:    6/2/2021

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