ModifiedCareSourcePolicy N/A

Nivolumab (Opdivo) — Oncology indications and authorization criteria (coverage criteria)

Defines medical necessity criteria, dosing, and authorization periods for nivolumab (Opdivo) across multiple cancer types for oncology prescribers and payer review.

Policy Summary

PayerCareSource

PolicyNivolumab (Opdivo) — Oncology indications and authorization criteria (coverage criteria)

Policy CodePolicy N/A

Change TypeMaterial revisions to indications, dosing, biomarkers, and prior‑therapy requirements

Effective DateN/A

Next Review DateN/A

Key ActionObtain prior authorization with documentation of diagnosis, age, line of therapy, required biomarkers, prior therapies when specified, and intended dosing regimen.

SourceLink

POLICY UPDATE CHANGES

Added ICE (ifosfamide, carboplatin, and etoposide) as combination option with brentuximab vedotin for classic Hodgkin lymphoma in relapsed/refractory disease.

Removed requirement that patient has tried three or more systemic regimens (including autologous stem cell transplant) for classical Hodgkin lymphoma; added options for primary treatment including combinations with AVD or Adcetris or as single agent.

Multiple new disease-specific indications were added (e.g., ampullary adenocarcinoma, bone cancer, Kaposi sarcoma, primary mediastinal large B-cell lymphoma, squamous cell skin cancer, thyroid, vaginal cancers, pediatric indications).

Numerous dosing regimen additions and removals (examples: added 240 mg q2w and 480 mg q4w options for certain indications; added mg/kg regimens for endometrial carcinoma and small cell lung cancer).

Changes to biomarker and mutation-related requirements for multiple tumor types (e.g., removal/addition of PD-L1 CPS and lists of actionable mutations for NSCLC and gastric/esophageal cancers).

~30+distinct cancer-specific entries

Trek Health ingests and normalizes Transparency in Coverage data and payer policy updates to give provider organizations a clear view of how commercial reimbursement behaves across markets, payers, and services. Our platform transforms raw payer disclosures into structured intelligence that supports contract evaluation, payer negotiations, and service line strategy. By combining market benchmarks with ongoing policy visibility, Trek helps teams identify variability, risk, and opportunity in commercial reimbursement. The result is faster insight, stronger negotiating positions, and more informed financial decisions.

Indication-specific Coverage Criteria

Indication-specific coverage criteria (multiple cancer types)

Covered when ALL criteria for the specific cancer indication are met (each indication lists its own A/B/C… requirements).

General per-indication structure: Each cancer indication requires documentation of patient age (usually ≥18 years unless pediatric age expansion is specified), disease status (eg, locally advanced, unresectable, recurrent, or metastatic, or resectable when neoadjuvant use is specified), tumor biomarker or mutation status when required (eg, MSI-H/dMMR, TMB-H, PD-L1 CPS, specific actionable mutations), prior therapy conditions when specified, that the medication is prescribed by or in consultation with an oncologist, and selection of an approved dosing regimen.

Individual tumor sections enumerate specific alternatives (eg, single agent OR in combination with ipilimumab or other agents) and list dosing options (240 mg q2w, 480 mg q4w, 360 mg q3w, or mg/kg regimens).

Selected molecularly defined lung cancer indications

Lung cancer / EGFR/ERBB2/NRG1 mutation guidance

EGFR/ERBB2/NRG1 mutation indications: Approve when the tumor harbors ONE of the following genomic alterations: EGFR exon 20 insertion (or specified EGFR non-exon19/L858R mutations such as S768I, L861Q, G719X), ERBB2 (HER2) mutation, OR NRG1 gene fusion; AND the patient does NOT have EGFR exon 19 deletion or L858R mutation, nor ALK, RET, or ROS1 rearrangements as exclusionary alterations.

Policy notes prior targeted therapy for some mutation-positive patients and documents examples of targeted agents; see tumor-specific entry for whether prior targeted therapy is required.

Neoadjuvant/resctable disease

Neoadjuvant and perioperative use

Neoadjuvant/resectable disease: Approve for neoadjuvant (perioperative) use when ALL of the following are met: patient has resectable disease (defined as tumor ≥4 cm or node positive), the medication is being used as neoadjuvant therapy, and dosing/combination regimen conforms to an approved option; approval duration for neoadjuvant use is limited (examples: up to 4 months for certain NSCLC entries; up to 3 months noted for other tumor types).4 months (example for NSCLC); up to 3 months (other tumors)

Resectable disease definition and neoadjuvant duration are specified in tumor-specific entries; combinations with platinum-doublet chemotherapy or other perioperative regimens are addressed per indication.

Indication-specific coverage summary

Covered when indication-specific criteria are met per disease-specific entries below (examples pulled from history/revision notes in this segment):

Classic Hodgkin Lymphoma: Coverage when patient has relapsed or refractory disease and nivolumab will be used as single agent or in combination with brentuximab vedotin (Adcetris) or ICE (ifosfamide, carboplatin, etoposide); prior requirement that patient had tried ≥3 systemic regimens (including autologous SCT) was removed and primary treatment options were expanded.

Added ICE as an allowed combination; primary treatment options broadened.

Esophageal / Esophagogastric Junction Carcinoma: Coverage includes neoadjuvant/perioperative or induction therapy options for patients planned for esophagectomy and for unresectable or metastatic disease per indication; PD-L1 CPS requirement (CPS ≥5) was removed for some options and MSI-H/dMMR tumor–directed neoadjuvant/perioperative options were added.

Biomarker and regimen criteria revised across updates.

Gastric Cancer: Coverage added for locoregional MSI-H/dMMR tumors as neoadjuvant/perioperative therapy and for unresectable locally advanced/recurrent/metastatic MSI-H/dMMR disease with combination options (eg, with ipilimumab) per tumor entry.

Coverage of nivolumab (Opdivo) is limited to the specific clinical scenarios and disease‑specific criteria listed in this policy. Requests that do not meet the Recommended Authorization Criteria for the applicable indication are not recommended for approval and may be denied. Criteria will be updated as new published data become available.

Several prior requirements and option criteria have been removed or revised across recent updates. Examples include the removal of a PD‑L1 CPS ≥5 requirement for certain esophageal/gastric approvals and changes to lists of actionable mutations used to determine eligibility for non‑small cell lung cancer. Verify the current, indication‑specific biomarker and prior‑therapy prerequisites in each disease section because these prerequisites have been explicitly modified in this revision history.

Use of nivolumab is considered not medically necessary when required biomarkers, mutation exclusions, prior systemic therapy requirements, or other disease‑state prerequisites specified for an indication are not met. The policy history documents multiple adjustments to such prerequisites; absence of the indication‑specific criteria (for example, lacking documented MSI‑H/dMMR, TMB‑H, PD‑L1 CPS where required, or prior targeted/chemotherapy when specified) would render a request inconsistent with medical necessity under this policy.

Dosing and Regimens

Regimen	Administration / Frequency	Notes (indication examples)
240 mg IV
Intravenous infusion every 2 weeks
Cited repeatedly as an approved option across multiple tumor indications (eg, neoadjuvant settings, anal carcinoma, urothelial carcinoma, pediatric Hodgkin lymphoma).
480 mg IV
Intravenous infusion every 4 weeks
Frequently listed as an alternative fixed-dose schedule for many indications (ampullary adenocarcinoma, anal carcinoma, biliary/other cancers).
360 mg IV
Intravenous infusion every 3 weeks
Included as a fixed-dose option for some indications (listed among standard dosing alternatives).
3 mg/kg IV
Weight‑based intravenous infusion (commonly every 2–3 weeks depending on indication)
Weight‑based regimen used for indications such as ampullary adenocarcinoma, sarcomas, pediatric Hodgkin lymphoma, and other tumor‑specific entries.
1 mg/kg IV
Weight‑based intravenous infusion every 3 weeks (documented as an option for some tumor types)
Present in weight‑based regimen lists for specific indications (see small cell lung cancer and selected sarcoma entries).
Combination regimens (example)
Varies by combination partner (eg, with ipilimumab, platinum‑doublet chemotherapy, brentuximab vedotin)
Multiple indications permit Opdivo as single agent or in combination (eg, ampullary adenocarcinoma with ipilimumab; neoadjuvant use with platinum doublet; Hodgkin lymphoma with brentuximab).

Revision note	Dosing regimens added or removed	Context / affected indications
Annual and selected revisions
Added 240 mg q2w and 480 mg q4w options; added mg/kg regimens (eg, 3 mg/kg q3w, 1 mg/kg q3w); added 360 mg q3w and 6 mg/kg q4w in some entries; removed or modified prior options in others.
Changes applied across multiple tumor sections (eg, Merkel cell carcinoma, melanoma, hepatic and GI indications, pediatric Hodgkin lymphoma, small cell lung cancer).
Removal of specific prerequisites and dosing adjustments
Removed certain dosing or prior‑therapy constraints (eg, removal of PD‑L1 CPS >=5 requirement; removal of transplant eligibility in Hodgkin lymphoma); dosing alternatives were likewise re-ordered or removed for select tumors.
Affected esophageal/gastric approvals, classic Hodgkin lymphoma, biliary tract cancer dosing rules and others as noted in history entries.
Heterogeneous updates noted in history summaries
Multiple tumor‑specific entries had dosing schedules added or moved between required vs optional lists (examples include addition of 480 mg q4w, reintroduction of mg/kg schedules, and addition/removal of 360 mg q3w).
Document history shows these changes span revisions through 2023–2025 and impact many indication sections (see HISTORY entries).

Biomarker and Mutation Requirements

MSI‑H / dMMR

BiomarkerMicrosatellite instability‑high (MSI‑H) or deficient mismatch repair (dMMR)

Required forAmpullary adenocarcinoma and other specified tumor indications where listed

DocumentationTumor testing demonstrating MSI‑H or dMMR status must be in the medical record

TMB‑H

BiomarkerTumor mutational burden‑high (TMB‑H)

ThresholdTMB‑H defined as tumor mutation burden ≥ 50 mutations/megabase (ultra‑hypermutated phenotype)

Indications

Therapy Line Requirements

first-line | second-line | salvage

Top-level distinctions used across tumor-specific entries to indicate when nivolumab is being used as initial, subsequent, or salvage therapy.

Line-of-therapy distinctions: Indications specify whether use is first-line (including first-line for metastatic disease or perioperative/neoadjuvant use), second-line/subsequent therapy, or salvage/re-induction settings; each tumor entry lists the applicable line and any required prior systemic or targeted therapies.

Documentation of prior therapies is required when an indication specifies subsequent therapy; see tumor-specific sections for exact prior therapy requirements.

first-line

First-line uses summarized where specified by tumor-type entries.

First-line: Certain tumor types include first-line use as an approved option when indicated (examples include select molecular subsets of NSCLC, ampullary adenocarcinoma when MSI‑H and used first‑line for metastatic disease, some biliary tract or other tumors per their entries). First-line approvals include tumor‑specific biomarker, histology, and combination regimen requirements.

Billing, Codes, and Durations

Prior auth / billing codes (unspecified in provided text)mixed

affected codes

Document references prior authorization and affected billing codes but specific CPT/HCPCS codes not listed in these chunks.

Ultra‑hypermutated phenotype threshold

ThresholdUltra‑hypermutated phenotype defined as tumor mutation burden ≥ 50 mutations/megabase

ContextReferenced for selection of indications with ultra‑hypermutant tumors (e.g., diffuse high‑grade glioma, selected sarcomas)

DocumentationProvide TMB test report showing mutations/megabase when requesting coverage under this criterion

Neoadjuvant approval duration (general)

IndicationNeoadjuvant use (general) — approval duration up to 3 months in some indications

ExampleMelanoma: added approval for up to 3 months when Opdivo used neoadjuvantly

Prescriber Requirements and Prior Authorization

Prior Authorization

Prior Authorization and Approval Durations

Prior authorization is required for use of this medication. Approvals are issued for the durations specified in the criteria (commonly up to 4 months for neoadjuvant use, or up to 1 year for most advanced/metastatic or subsequent therapy indications). Ensure the requested duration matches the indication-specific authorization period.

Typical approval durations: 4 months for neoadjuvant therapy when specified; 1 year for most advanced, metastatic, or subsequent-therapy indications.
Dosing frequency/administration schedules must be consistent with the FDA‑approved regimens listed in the clinical criteria.

Denial Risk

Biomarker and Therapy Prerequisites — Provide Documentation or Risk Denial

Document tumor biomarker and prior therapy status when required by the indication. Requests may be denied if required biomarker testing (e.g., EGFR, ALK, ROS1, NTRK/NRG1, ERBB2/HER2, MSI‑H/dMMR, PD‑L1 where applicable) or evidence of prior targeted or systemic therapy is not provided.

Key Definitions

Resectable disease (neoadjuvant context)

DefinitionResectable disease: tumors ≥ 4 cm or node positive (used in neoadjuvant context)

ContextRequired criterion when approving neoadjuvant therapy (e.g., NSCLC, esophagectomy planning)

DocumentationProvide imaging/pathology evidence documenting tumor size or nodal status

Ultra‑hypermutated phenotype (definition)

DefinitionUltra‑hypermutated phenotype = tumor mutation burden ≥ 50 mutations/megabase

UseUsed to define eligibility for specific high‑TMB indications (eg, diffuse high‑grade glioma, select sarcomas)

Policy Revision Notes

02/12/2025annual_revision

Classic Hodgkin lymphoma: added ICE (ifosfamide, carboplatin, etoposide) as a combination option with brentuximab vedotin; removed requirement for three or more systemic regimens and added primary treatment options including AVD, Adcetris, or single-agent use.

03/20/2024selected_revision

Urothelial carcinoma: removed requirement that the patient try at least one other chemotherapy regimen or be at high risk of recurrence after radical resection.

03/26/2025selected_revision

Melanoma: revised pediatric age from ≥18 to ≥12 years for certain indications and added neoadjuvant approval for up to 3 months of treatment.

Policy Summary

PayerCareSource

PolicyNivolumab (Opdivo) — Oncology indications and authorization criteria (coverage criteria)

Policy CodePolicy N/A

Change TypeMaterial revisions to indications, dosing, biomarkers, and prior‑therapy requirements

Effective DateN/A

Next Review DateN/A

Key ActionObtain prior authorization with documentation of diagnosis, age, line of therapy, required biomarkers, prior therapies when specified, and intended dosing regimen.

SourceLink

On This Page

second-line

Second-line and subsequent therapy uses summarized where specified by tumor-type entries.

Second-line / subsequent therapy: Many tumor indications authorize nivolumab as second-line or subsequent therapy when prior systemic therapy conditions are met (examples: cervical cancer, small cell lung cancer, pancreatic cancer in combination with ipilimumab for TMB‑H tumors, and numerous other tumor-specific entries). Prior therapy documentation should be provided when required by the indication.

History notes indicate prior therapy requirements have been added, removed, or modified for specific tumor types—review the tumor entry for current prerequisites.

Documentation Required

Prescriber and Documentation Requirements

The prescriber must be an oncologist or the request must include documentation of consultation with an oncologist. Include patient age, disease stage, tumor biomarker results, prior lines of therapy (with agents and dates), and the planned regimen/ dosing schedule.

Prescriber: oncologist or documented oncologist consultation required.
Essential documentation: patient age, stage of disease (resectable, locally advanced, metastatic, recurrent), relevant biomarker/molecular testing results, prior systemic or targeted therapies (agents, dates, outcomes), and intended dosing regimen.

Step Therapy

Prior Therapy Requirements — Document Previous Targeted or Systemic Treatments

When prior therapy is specified by the indication (for example, prior targeted drug therapy for a specific mutation, prior platinum‑doublet chemotherapy, neoadjuvant therapy received), supply clear documentation of those treatments. Indications that require the medication as subsequent therapy must show prior use of first‑line agents when listed.

If the criterion requires prior targeted therapy for an actionable mutation, include records of the targeted agent(s) used (e.g., afatinib, osimertinib, erlotinib, dacomitinib) and the treatment timeframe.
If prior systemic chemotherapy (e.g., platinum‑doublet) or chemoimmunotherapy is required, include regimen details (agents, cycles, dates) and reason for discontinuation if applicable.
For approvals contingent on neoadjuvant or adjuvant treatment history, document the neoadjuvant/adjuvant regimen and treatment dates.

Documentation Required

Biomarker and Prior Therapy Documentation — Support Concurrent Requirements

Support requests with both biomarker status and prior therapy documentation when criteria require both. Examples include MSI‑H/dMMR status for certain solid tumors or specific mutation positivity plus demonstration of prior therapy lines when the medication is intended as subsequent therapy.

Provide tumor testing results (e.g., MSI‑H/dMMR, ERBB2/HER2 mutation, NRG1 fusion, EGFR exon 20) alongside prior therapy history when the indication requires both.
When the policy lists multiple mutually exclusive mutation requirements (e.g., absence of EGFR exon 19 deletion or exon 21 L858R, absence of ALK/ROS1 rearrangements), document the full panel results to show criteria are met.
If prior immunotherapy or chemotherapy exclusions/requirements are part of the criteria, include documentation showing whether the patient has received those agents.

04/30/2025selected_revisionLatest

Multiple updates: added pediatric Hodgkin lymphoma age expansion and numerous new disease-specific indications (ampullary adenocarcinoma, bone cancer, Kaposi sarcoma, primary mediastinal large B-cell lymphoma, squamous cell skin cancer, thyroid, vaginal cancers); added and removed multiple dosing options (including 240 mg q2w, 480 mg q4w, 360 mg q3w and mg/kg regimens); and modified biomarker prerequisites (PD-L1 CPS requirements removed for some GI indications; actionable mutation lists for NSCLC revised).