Coverage guidance for use of tumor treating fields (TTF) therapy (Optune family) in adults with glioblastoma and other cancers; defines evidence summaries, regulatory status, and guideline context that inform medical necessity decisions.
Policy Summary
PayerPremera Bluecross
PolicyTumor Treating Fields Therapy
Policy CodePolicy 1.01.29
Change TypeNo material changes
Effective Date
Next Review Date
Key ActionObtain prior authorization and document that the indication aligns with FDA-approved labeling and required clinical information (diagnosis, prior therapies, disease site).
No material clinical or coverage changes in this revision.
+4.9 moEF-14 OS benefit
+2.7 moEF-14 PFS benefit
10.3 moRecurrent GBM pooled OS
InvestigationalMPM stance
InvestigationalNSCLC stance
Annual
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Review cadence
Coverage Criteria for Tumor Treating Fields (TTFields)
Initial (newly diagnosed) GBM — adjunct to maintenance temozolomide
Covered when ALL of the following are met (newly diagnosed GBM setting supported by highest-quality evidence):
Newly diagnosed GBM (adjunctive use): Individual has newly diagnosed, histologically confirmed glioblastoma (GBM) that is supratentorial and is an adult (per FDA labeling, ≥22 years of age).
TTFields (Optune) is used as an adjunct to standard maintenance temozolomide following maximal debulking surgery and completion of radiation therapy; EF-14 randomized trial demonstrated a 2.7-month PFS and 4.9-month OS improvement with TTF + temozolomide.
Recurrent/progressive GBM
Considered investigational/insufficient evidence when used as:
Recurrent/progressive GBM (adjunct or alternative): TTF therapy for progressive or recurrent GBM used as an adjunct to or alternative to standard medical therapy after prior surgery, radiation, and chemotherapy.
A single RCT did not show superiority for overall survival versus physicians' choice chemotherapy; pooled evidence yields median OS ~10.3 months; evidence is insufficient to conclude improvement in net health outcome and high-quality prospective RCTs are needed.
Other tumor types (MPM, NSCLC)
Insufficient evidence / investigational for other indications:
Malignant pleural mesothelioma (MPM): TTF therapy delivered with Optune Lua (NovoTTF-100L) used concurrently with pemetrexed and platinum chemotherapy for unresectable, locally advanced, or metastatic MPM.
Evidence limited to a single-arm prospective study (median OS 18.2 months) and small retrospective series without comparator groups; insufficient to determine improved net health outcome.
Metastatic non-small cell lung cancer (NSCLC): TTF therapy (Optune Lua) used with an immune checkpoint inhibitor or docetaxel for metastatic NSCLC after progression on platinum-based therapy.
Open-label RCT (LUNAR) found a 3.3-month OS increase but no PFS or ORR benefit; trial limitations (no sham control, limited baseline molecular testing, evolving standards) render evidence insufficient to determine net health outcome.
Presence of initial and reauthorization criteria
Policy includes defined initial and reauthorization criteria for TTFields therapy (details in prior chunks).
Defined initial and reauthorization criteria: Initial and reauthorization criteria for TTFields were defined (added 10/01/21) and remain in effect; wording standardized from 'patient' to 'individual' in 2023.
See prior policy sections for the exact clinical elements required at initial authorization and for renewal requests (e.g., diagnosis confirmation, prior therapies, site of disease, and performance status documentation).
Use of Tumor Treating Fields (TTF) outside the supratentorial brain for glioblastoma or for other tumor types without FDA-labeled indications is not supported by the evidence summarized in this policy and may be excluded from coverage. The FDA-approved labeling and the policy specifically reference supratentorial GBM indications and the approved concurrent regimens (e.g., Optune with temozolomide for newly diagnosed, supratentorial GBM; Optune Lua for malignant pleural mesothelioma with pemetrexed and platinum; Optune Lua for metastatic NSCLC with concurrent therapies). Providers requesting authorization for disease sites or settings not addressed by FDA labeling should expect review against the evidence and may face denial if the use is outside labeled indications and lacks sufficient comparative evidence of net health benefit.
This medical policy and its coverage guidance do not apply to Medicare Advantage plans. Members and providers should consult the member benefit booklet or contact a customer service representative to determine coverage under Medicare Advantage or other specific benefit plan provisions.
The evidence is insufficient to conclude that TTF therapy improves net health outcomes when used for recurrent or progressive glioblastoma, as the single randomized trial did not show superiority for overall survival and pooled analyses remain inconclusive. Similarly, for malignant pleural mesothelioma (MPM) the available data are limited to single-arm and small retrospective studies without comparator groups, and for metastatic non–small cell lung cancer (NSCLC) the pivotal open-label trial (LUNAR) has methodological limitations; therefore, TTF use in these indications is considered to have insufficient evidence to establish medical necessity.
Accordingly, TTF therapy is designated investigational for malignant pleural mesothelioma and non–small cell lung cancer in this policy. Although the FDA has cleared or approved specific Optune family devices for MPM and, more recently, for metastatic NSCLC in defined treatment combinations, the clinical evidence—single-arm studies for MPM and an open-label RCT with limitations for NSCLC—does not provide sufficient high-quality comparative data to demonstrate improved net health outcomes, and the policy therefore considers these indications investigational.
Regimens and Trial Context
Regimen
Indication / Setting
Coverage status
Supporting evidence / notes
Optune (TTF) concomitant with maintenance temozolomide
Newly diagnosed, supratentorial glioblastoma following maximal debulking surgery and completion of radiation therapy; used as adjunct to standard maintenance temozolomide
Covered
EF-14 randomized trial: TTF + temozolomide increased PFS by 2.7 months and OS by 4.9 months; systematic review pooled median OS 21.7 months and PFS 7.2 months supporting net health benefit
Regimen
Indication / Setting
Coverage status
Supporting evidence / notes
Optune Lua (NovoTTF-100L) with pemetrexed + platinum
Unresectable, locally advanced, or metastatic malignant pleural mesothelioma used concurrently with pemetrexed and cisplatin or carboplatin
Investigational/insufficient evidence
Single-arm prospective study (n=80) reported median OS 18.2 months; no comparator group, evidence insufficient to determine improvement in net health outcome despite FDA approval for this indication
Regimen
Indication / Setting
Coverage status
Supporting evidence / notes
Optune Lua + pembrolizumab or docetaxel (LUNAR trial context)
Metastatic non-small cell lung cancer after progression on or after platinum-based chemotherapy; TTF used with an immune checkpoint inhibitor or docetaxel
Investigational/insufficient evidence
Open-label RCT (LUNAR, n=276) found a 3.3-month OS increase but no PFS or ORR benefit; trial limitations (no sham, limited baseline molecular testing, evolving standards of care) lead to insufficient evidence to determine net health outcome
Regimen
Indication / Setting
Coverage status
Supporting evidence / notes
Tumor Treating Fields plus maintenance temozolomide (as studied in EF-14)
Maintenance therapy for newly diagnosed supratentorial glioblastoma in adults (adjunct to temozolomide) following surgery and radiation
Covered
EF-14 randomized clinical trial demonstrated PFS improvement of 2.7 months and OS improvement of 4.9 months with TTF + temozolomide; systematic reviews support clinical benefit
Regimen
Indication / Setting
Coverage status
Supporting evidence / notes
TTFields with pemetrexed and platinum (STELLAR trial context)
First-line combination therapy for unresectable malignant pleural mesothelioma with pemetrexed and cisplatin or carboplatin
Investigational/insufficient evidence
STELLAR single-arm phase 2 trial reported outcomes for TTF + pemetrexed/platinum; absence of a comparator limits conclusions about net health outcome and evidence is insufficient
Coding and Billing Codes
Regulatory product codesmixed
NZK
FDA product code associated with TTF devices
QGZ
FDA product code associated with TTF devices
Historical HCPCS codes referenced in historyHCPCS
A9900
Previously listed miscellaneous HCPCS code (removed later per history)
E1399
Previously listed miscellaneous HCPCS code (removed later per history)
Covered HCPCS/Device CodesHCPCSCovered
HCPCS codes listed elsewhere in policy
Current HCPCS codes for TTFields devices (see earlier policy sections)
Provider Actions, Authorization, and Documentation
Prior Authorization
Prior Authorization Required — Indication Must Align with FDA Labeling
Prior authorization is required. Confirm the indication aligns with the FDA-approved labeling for the specific Optune product being requested (e.g., Optune for newly diagnosed supratentorial GBM with temozolomide, Optune as an alternative for recurrent supratentorial GBM after prior chemotherapy). Requests for uses outside the device's FDA-labeled indications are subject to denial as investigational unless supported by applicable contract language or explicit medical review.
FDA indications vary by product and diagnosis (newly diagnosed GBM with temozolomide; recurrent supratentorial GBM after prior chemotherapy)
Documentation Required
Required Clinical Documentation
Provide documentation that supports the requested indication and clinical need. Submit treatment history, diagnostic confirmation, and functional status as detailed below.
Line of Therapy Definitions and Applicability
first-line
First-line setting (definition and covered scenario):
First-line (newly diagnosed) GBM: Use as adjunct to maintenance temozolomide following maximal safe resection and completion of radiotherapy for newly diagnosed supratentorial GBM.
Supported by EF-14 randomized trial and designated in FDA labeling and NCCN guidance as a first-line maintenance adjunct when criteria are met.
salvage
Salvage setting (definition and evidence stance):
Salvage (recurrent) GBM: Use after recurrence/progression as adjunct or alternative to standard salvage medical therapy (physician's choice chemotherapy).
Single RCT in recurrent GBM did not demonstrate superiority for OS; evidence insufficient to support medically necessary designation for salvage use.
Biomarker Considerations
inv-26: MGMT promoter methylation
BiomarkerMGMT promoter methylation status (O6-methylguanine-DNA methyltransferase) is referenced in NCCN guidance as part of treatment considerations for glioblastoma (methylated, unmethylated, or indeterminate statuses noted)
Role in treatment selectionNCCN lists TTF plus temozolomide as a Category 1 option for initial treatment of glioblastoma regardless of MGMT promoter methylation status, but methylation status informs other treatment options (e.g., temozolomide-only choices)
Performance status contextNCCN guidance couples MGMT promoter methylation consideration with KPS ≥60 when framing treatment options for newly diagnosed GBM
Anatomic limitationAlternating electric field therapy (TTF) is an option only for individuals with supratentorial disease per NCCN guidance
Definitions and Device Names
inv-21: Optune/Optune Lua/Optune Gio brand names and device mapping
Brand namesOptune, Optune Lua, Optune Gio are the brand names used for NovoTTF device family (Optune Lua = NovoTTF-100L; Optune Gio introduced in 2023)
Device-family mappingNovoTTF-100A / NovoTTF-200A systems marketed as Optune; NovoTTF-100L marketed as Optune Lua; newer variants receive suffixes to delineate indications
Regulatory noteFDA approvals and name changes documented: Optune name change (Sept 2014), Optune Lua (NovoTTF-100L) approval for MPM (May 2019), Optune Gio renaming (2023)
FDA product codesAssociated FDA product codes: NZK; QGZ (applies to TTF devices)
DefinitionTumor Treating Fields (TTFields) therapy: locoregional antimitotic treatment that delivers alternating electric fields to tumors via portable devices (Optune family)
Background on TTFields
Tumor Treating Fields (TTFields) are a locoregional, antimitotic therapy delivered by portable devices in the Optune family that apply alternating electric fields to tumor sites. The technology received FDA premarket approval for recurrent, supratentorial glioblastoma (NovoTTF-100A/Optune) and was later expanded to include use in combination with temozolomide for newly diagnosed, supratentorial GBM following maximal debulking surgery and radiation. Device variants (e.g., Optune Lua, Optune Gio) have been developed and cleared or approved for other tumor types under specified concurrent regimens. Clinical trial evidence supporting TTF includes the EF-14 randomized trial showing improvements in progression-free survival and overall survival for newly diagnosed GBM when added to maintenance temozolomide; other indications have more limited or lower-quality evidence, which informs the coverage distinctions in this policy.
Policy Revision History
2013-10-14policy_created
New policy created based on literature through June 3, 2013 and initially considered investigational.
2016-09-01coverage_change
Policy statement changed to medically necessary when criteria are met.
2018-09-01coverage_change
Title changed to 'Tumor Treating Fields Therapy' and policy noted may be considered medically necessary in conjunction with maintenance temozolomide for newly diagnosed glioblastoma; investigational for other indications.
Policy Summary
PayerPremera Bluecross
PolicyTumor Treating Fields Therapy
Policy CodePolicy 1.01.29
Change TypeNo material changes
Effective Date
Next Review Date
Key ActionObtain prior authorization and document that the indication aligns with FDA-approved labeling and required clinical information (diagnosis, prior therapies, disease site).
Histologic or cytologic confirmation of glioblastoma multiforme (GBM) and documentation of tumor location (supratentorial)
For newly diagnosed GBM: documentation of maximal debulking surgery and completion of radiation therapy and plan to continue temozolomide concomitantly with Optune
For recurrent GBM: documentation of prior chemotherapy and that surgical and radiation options have been exhausted or are not appropriate
Relevant imaging reports (MRI/CT) demonstrating disease status
Treatment timeline and dates (surgery, radiation, chemotherapy)
Baseline and recent performance status (e.g., Karnofsky Performance Scale) and any comorbidities affecting use of the device
For reauthorization: objective evidence of stability or clinical benefit (tolerance, compliance, absence of progressive disease) and documentation of continued concomitant therapy when indicated
Documentation Required
Member Benefit Verification Required
Verify member benefits and coverage limitations prior to authorization and device provision. Coverage is subject to the limits and conditions of the member's benefit plan; this policy does not apply to Medicare Advantage members.
Confirm member's plan covers devices/supplies and durable medical equipment where applicable
Check for any benefit-specific limits, prior authorization rules, or exclusions
If the requested use is outside FDA-labeled indications, check contract language for allowance or obtain medical review determination
Contact member services for eligibility and benefits verification
Step Therapy
Initial Authorization and Reauthorization Steps
Outline of initial authorization and reauthorization steps to support medical necessity determinations.
Initial authorization: submit required clinical documentation (see above) demonstrating that the individual's clinical presentation matches the FDA-labeled indication for the specific Optune product requested and that prior treatments (surgery, radiation, chemotherapy) were performed as indicated by the label
Reauthorization/continuation: provide clinical evidence of benefit or clinical stability (e.g., imaging showing no progression, maintained or improved performance status), documentation of adherence to device use, and confirmation that concomitant standard therapy (e.g., temozolomide for newly diagnosed GBM) continues when required by the labeled indication
Denial risk: reauthorization may be denied if there is documented disease progression, lack of clinical benefit, nonadherence to therapy, or if ongoing use is for an indication not supported by FDA labeling or the member's benefit plan
first-line | maintenance | recurrent
Indications studied across lines of therapy include the following:
First-line | maintenance | recurrent: TTFields have been evaluated as maintenance therapy with temozolomide for newly diagnosed GBM, and studied in recurrent GBM as well as in other tumor types (e.g., MPM and metastatic NSCLC) in clinical trials.
Coverage stance varies by indication: covered with criteria for newly diagnosed GBM maintenance; investigational/insufficient evidence for recurrent GBM and other tumor types.
Mode of useApplied with a wearable/portable delivery system (NovoTTF/Optune series) using transducer arrays placed on the scalp for supratentorial brain tumors
Indication examplesFDA-labeled uses include recurrent supratentorial GBM, newly diagnosed GBM with temozolomide, MPM with pemetrexed/platinum (Optune Lua), and metastatic NSCLC with concurrent drugs (Optune Lua)
Therapeutic intentIntended as a locoregional, noninvasive antimitotic modality — used as adjunctive therapy (e.g., with maintenance temozolomide) or as an alternative/adjunct in recurrent disease depending on indication
2019-10-01investigational_listing
Malignant pleural mesothelioma was added to the list of conditions for which the therapy is considered investigational.
2021-10-01criteria_addition
Defined initial and reauthorization criteria were added for clarity (annual review approved September 23, 2021).
2023-10-01editorial_change
Wording changed from 'patient' to 'individual' throughout the policy for standardization during the annual review approved September 11, 2023.
2024-10-01editorial_refinement
Minor editorial refinements to the Policy Guidelines section during the annual review approved September 9, 2024; intent unchanged.
2025-10-01investigational_listing
Non-small cell lung cancer was added to the list of conditions for which the therapy is considered investigational (annual review approved September 9, 2025).
2026-02-10minor_updateLatest
Minor update to Karofsky Performance Scale link and reference added (02/10/26).