TTFields Optune Lua

Overview

Tumor Treating Fields (TTFields) represent a first-in-class, non-invasive cancer treatment that uses alternating electric fields to disrupt cancer cell division. The NovoTTF-100L system — now branded Optune Lua — became the first FDA-approved mesothelioma treatment in more than 15 years when it received Humanitarian Device Exemption (HDE) approval on May 23, 2019. Approval was based on the phase 2 STELLAR trial (NCT02397928), in which 80 patients with unresectable malignant pleural mesothelioma (MPM) treated with TTFields plus pemetrexed and platinum-based chemotherapy achieved a median overall survival of 18.2 months — compared to a historical control of 12.1 months with chemotherapy alone.

TTFields therapy is delivered continuously via a portable medical device weighing just 1.2 kg (second-generation model) with transducer arrays placed on the patient's torso, with a recommended usage of at least 18 hours per day. Often described as a "fourth modality" in cancer treatment — alongside surgery, radiation, and systemic therapy — TTFields have demonstrated antitumor effects through multiple mechanisms including mitotic spindle disruption, DNA damage repair interference, immune activation, and enhanced chemotherapy sensitivity. The only device-related adverse events are mild-to-moderate skin reactions beneath the arrays, with no additional systemic toxicity beyond what is expected from chemotherapy.

As of 2026, more than 110 U.S. hospitals are certified to offer TTFields for mesothelioma, and the therapy is commercially available in multiple countries including Austria, France, Germany, Israel, Japan, and Switzerland.

TTFields / Optune Lua
Device Name	Optune Lua (NovoTTF-100L / NovoTTF-200T)
Manufacturer	NovoCure Ltd.
FDA Approval	May 23, 2019 (HDE)
Indication	Unresectable, locally advanced or metastatic MPM
Frequency	150 kHz
Pivotal Trial	STELLAR (NCT02397928)
Median OS	18.2 months (vs 12.1 historical)
1-Year Survival	62.2%
Device Weight	1.2 kg (2nd gen)
Daily Usage	≥18 hours/day recommended
Estimated Cost	~$21,000/month
Approved Indications	MPM, GBM (new & recurrent), NSCLC

TTFields for mesothelioma at a glance:

• 50% longer survival vs chemotherapy alone — patients receiving TTFields plus pemetrexed/platinum achieved 18.2 months median overall survival compared to 12.1 months with chemotherapy alone
• Epithelioid patients survive nearly twice as long — those with epithelioid histology reached 21.2 months median OS versus 12.1 months for non-epithelioid subtypes
• First new mesothelioma treatment in 15 years — TTFields received FDA approval in May 2019, the first since pemetrexed was approved in 2004
• 97% of patients achieved disease control — only 3% of STELLAR participants experienced progressive disease on treatment
• No systemic side effects from the device — unlike chemotherapy, TTFields cause only localized skin reactions beneath the arrays, with no nausea, hair loss, or organ toxicity
• Mesothelioma cells are among the most TTFields-sensitive cancers — preclinical studies show higher vulnerability compared to glioblastoma and lung cancer cell lines
• Device weighs less than a laptop — the second-generation Optune Lua weighs 1.2 kg total, down 56% from the original 2.7 kg model
• Exceptional long-term responses documented — one STELLAR patient remained in remission for over 8 years after starting treatment
• LUNAR trial validates the TTFields-immunotherapy combination — in lung cancer, TTFields plus immunotherapy extended survival to 19.0 months versus 10.8 months for immunotherapy alone, supporting future mesothelioma studies
• Available at 110+ certified U.S. hospitals — patients can access TTFields therapy through NovoCure's network of trained treatment centers nationwide

Key Facts

Metric	Finding
STELLAR Median Overall Survival	18.2 months (95% CI: 12.1–25.8; N=80 unresectable MPM patients)
Epithelioid Subtype Median OS	21.2 months (n=53 epithelioid) vs 12.1 months (n=21 non-epithelioid)
Historical Control Median OS	12.1 months (Vogelzang 2003 pemetrexed + cisplatin phase 3 RCT)
1-Year Survival Rate	62.2% (STELLAR intent-to-treat population)
2-Year Survival Rate	41.9% (STELLAR intent-to-treat population)
Median Progression-Free Survival	7.6 months overall (95% CI: 6.7–8.6); 8.3 months epithelioid; 6.5 months non-epithelioid
Objective Response Rate	40% (29/72 evaluable patients achieved partial response)
Disease Control Rate	97% (PR 40% + SD 57%; only 3% progressive disease)
Dermatologic Adverse Events	58% any grade; 53% grade 1-2 dermatitis; 6% grade 3-4 (meta-analysis, N=192)
FDA Approval	May 23, 2019 — Humanitarian Device Exemption (H180002) for unresectable MPM
Device Compliance (STELLAR)	Median 16.3 hours/day during first 3 months; recommended minimum 18 hours/day (75%)

What Are Tumor Treating Fields?

Tumor Treating Fields (TTFields) are low-intensity (1–3 V/cm), intermediate-frequency (100–300 kHz) alternating electric fields delivered non-invasively to tumors through insulated transducer arrays placed on the skin. The therapy exploits the geometrical shape and electrical properties of dividing cells, making rapidly proliferating cancer cells susceptible to the electric field's effects while sparing most normal, non-dividing cells. For mesothelioma and non-small cell lung cancer (NSCLC), the frequency is set at 150 kHz, while glioblastoma (GBM) uses 200 kHz — the optimal frequency inversely correlates with cell size.

Mechanisms of Cancer Cell Destruction

TTFields exert antitumor effects through multiple complementary mechanisms that have been progressively elucidated over two decades of research:

Mitotic Spindle Disruption: During metaphase, TTFields interfere with the alignment of highly polarized tubulin subunits, preventing proper mitotic spindle assembly. This reduces the ratio of polymerized to total tubulin, leading to cell cycle arrest and aberrant mitosis. The landmark 2015 study by Giladi and colleagues in Scientific Reports demonstrated this effect using live-cell imaging and biochemical analysis.

Dielectrophoretic Movement: During telophase, the hourglass shape of dividing cells creates a non-uniform electric field that drives polar macromolecules and organelles toward the cleavage furrow, disrupting cell integrity and leading to defective cytokinesis.

DNA Damage Repair Interference: TTFields downregulate Fanconi anemia (FA)-BRCA DNA repair pathway genes, inducing a "BRCAness" state that enhances sensitivity to DNA-damaging chemotherapies like cisplatin. This molecular mechanism provides the scientific rationale for combining TTFields with platinum-based chemotherapy.

Immune Activation: TTFields-treated cancer cells release damage-associated molecular patterns (DAMPs) including HMGB1, calreticulin, and ATP, triggering immunogenic cell death. They also activate the cGAS/STING pathway and AIM2 inflammasomes, producing proinflammatory cytokines and type 1 interferons — effectively converting tumors from immunologically "cold" to "hot."

Membrane Permeability: TTFields reversibly alter cancer cell membrane structure, increasing permeability to chemotherapeutic agents. This effect appears specific to neoplastic cells and was confirmed by electron microscopy.

Cell Motility Inhibition: Through disruption of microtubule organization and activation of GEF-H1/RhoA/ROCK signaling, TTFields reduce cancer cell migration and invasion — potentially limiting metastatic spread.

Why Mesothelioma Is Especially Sensitive to TTFields

Preclinical studies have found that mesothelioma cell lines are among the most sensitive to TTFields treatment across all cancer types studied, both in terms of cell viability and clonogenic survival. This high sensitivity may relate to increased DNA double-strand break formation, elevated expression of cell cycle arrest proteins, and reduced FA-BRCA pathway protein expression observed in mesothelioma cells under TTFields treatment. Additionally, mesothelioma grows as a superficial tumor on thoracic pleural surfaces, making it anatomically accessible to electric field delivery through the chest wall.

Mannarino and colleagues further demonstrated that epithelioid mesothelioma cells are more sensitive to TTFields than sarcomatoid cells, with a distinct G2/M-phase block observed in epithelioid cells versus a milder general cell cycle delay in sarcomatoid cells. This aligns with STELLAR clinical findings where epithelioid patients achieved superior outcomes.

How Does the Optune Lua Device Work?

System Components

The Optune Lua Treatment Kit consists of several integrated components designed for continuous, portable use:

• Electric Field Generator: A portable device that produces TTFields at preset parameters — 150 kHz frequency, 1.414 A RMS maximum output, with an average field intensity of 0.7 V/cm delivered to the lungs
• Insulated Transducer Arrays: Four adhesive patches containing ceramic disc electrodes (large arrays: 20 discs; small arrays: 13 discs) embedded in a flexible circuit board with hydrogel and thermistors for temperature monitoring
• Rechargeable Batteries: Four batteries included, each lasting approximately one hour of operation
• Power Supply: For stationary use (overnight or while seated)
• Connection Cable and Carrying Bag: Over-the-shoulder bag for daily portability

Device Evolution

Feature	1st Generation (NovoTTF-100L)	2nd Generation (Optune Lua)
Total Weight	2.7 kg (6 lbs)	1.2 kg (2.7 lbs)
Device Weight	0.9 kg	0.7 kg
Battery Weight	1.8 kg	0.5 kg
Array Design	ILE model	Improved ITE model (more flexible)
Dimensions	Device: 21 × 21 × 4.5 cm; Battery: 21 × 21 × 2.8 cm	18 × 5.8 × 19 cm (integrated)

Array Placement and Compliance

Array placement is personalized for each patient based on tumor location, patient gender, and body size. Positions are determined using NovoCure's Clinical Practice Guidelines and the treating physician's judgment, supported by NovoCure's TorsoMAX software for generating digital layout maps.

TTFields therapy is administered continuously with a recommended minimum of 18 hours per day (75% of each 24-hour period). The device automatically records daily usage data in internal log files, generating monthly reports for adherence tracking. In the STELLAR trial, the median daily usage during the first 3 months was 16.3 hours per day. Real-world data from a single U.S. center reported a median of 12.5 hours per day, with investigators citing hot or humid climate and patient frailty as contributing factors.

Arrays must be replaced at least twice per week (every 4 days at most), with array position shifted by 1–2 cm at each change to reduce skin irritation. Patients should have at least 12 extra transducer arrays on hand at all times.

What Did the STELLAR Trial Show?

The STELLAR study (EF-23; NCT02397928) is the landmark clinical trial that established TTFields as a viable treatment option for malignant pleural mesothelioma and formed the basis for FDA approval.

Trial Design

STELLAR was a prospective, international, phase 2, single-arm study that evaluated TTFields therapy delivered to the thorax in combination with standard first-line chemotherapy for unresectable MPM. The study enrolled 80 patients at 12 European sites from February 2015 to March 2017. Treatment consisted of continuous TTFields at 150 kHz (≥18 hours/day) via the NovoTTF-100L system plus up to 6 cycles of pemetrexed with platinum chemotherapy (cisplatin or carboplatin at investigator's choice). After completing chemotherapy, patients who remained progression-free continued TTFields alone as maintenance until disease progression, unacceptable toxicity, or patient decision.

Efficacy Results

Endpoint	Overall (N=80)	Epithelioid (n=53)	Non-Epithelioid (n=21)
Median OS	18.2 months (95% CI: 12.1–25.8)	21.2 months	12.1 months
1-Year Survival	62.2%	—	—
2-Year Survival	41.9%	—	—
Median PFS	7.6 months (95% CI: 6.7–8.6)	8.3 months	6.5 months
Objective Response Rate	40%	—	—
Disease Control Rate	97%	—	—

The median OS of 18.2 months compared favorably to the historical control of 12.1 months from the pivotal Vogelzang 2003 study of pemetrexed plus cisplatin. The median duration of response was 5.7 months. Among 72 evaluable patients, 29 achieved partial response (40%) and 41 had stable disease (57%), yielding a disease control rate of 97% with only 3% demonstrating progressive disease.

How Does STELLAR Compare to Other Landmark Trials?

Trial	Treatment	Phase	Median OS
STELLAR (2019)	TTFields + pem/plat	Phase 2 (single-arm)	18.2 months
Vogelzang (2003)	Pemetrexed + cisplatin	Phase 3 (RCT)	12.1 months
MAPS (2016)	Pem + cis + bevacizumab	Phase 3 (RCT)	18.8 months
CheckMate 743 (2021)	Nivolumab + ipilimumab	Phase 3 (RCT)	18.1 months

Limitations of the STELLAR Trial

Independent reviewers have identified important limitations inherent to STELLAR's single-arm, phase 2 design:

• No randomized control group — efficacy was compared only to historical controls, making it impossible to attribute the survival benefit solely to TTFields
• Potential sampling bias in a heterogeneous cancer like pleural mesothelioma
• The FDA's HDE approval statement explicitly notes that "the effectiveness of this device for this use has not been demonstrated"
• Cross-trial comparisons with different patient populations and eligibility criteria are inherently unreliable

However, the sample size (N=80) was relatively large for a mesothelioma trial, and baseline patient characteristics were comparable to those in other first-line MPM studies such as MAPS and LUME-Meso.

Long-Term Survivor Cases

Two notable long-term cases from the STELLAR study have been reported in the peer-reviewed literature:

• A 63-year-old male with stage 4 epithelioid MPM who achieved TTFields usage of ≥75% per day remained in remission for over 8 years after completing 4.5 months of combined TTFields/chemotherapy followed by TTFields maintenance
• A 52-year-old male with stage 3 MPM who received TTFields therapy for 16 months achieved progression-free survival well beyond median expectations

Both cases achieved the recommended 75% daily usage threshold, supporting the dose-response relationship between TTFields usage time and outcomes.

How Did TTFields Receive FDA Approval?

The Humanitarian Device Exemption Pathway

The NovoTTF-100L System received FDA approval on May 23, 2019 under the Humanitarian Device Exemption (HDE) pathway (HDE number: H180002). The HDE pathway was created to encourage development of treatments for rare diseases affecting fewer than 8,000 patients per year in the United States — mesothelioma qualifies with approximately 3,000 new cases annually.

The approved indication is the treatment of adult patients with unresectable, locally advanced or metastatic malignant pleural mesothelioma, to be used concurrently with pemetrexed and platinum-based chemotherapy. Under HDE, the effectiveness threshold is lower than for Premarket Approval (PMA) — the device must show "probable benefit" rather than demonstrated effectiveness.

This was the first FDA-approved mesothelioma treatment in more than 15 years — since pemetrexed received approval in 2004.

Regulatory Status as of 2026: Still HDE-Only, No PMA Submitted

As of early 2026, Optune Lua for malignant pleural mesothelioma remains approved exclusively under the Humanitarian Device Exemption pathway. NovoCure's 2025 Annual Report (Form 10-K, filed February 2026) explicitly confirms that the mesothelioma indication has not been moved to the higher Premarket Approval (PMA) pathway. No PMA application for the mesothelioma indication has been submitted, and no phase 3 randomized controlled trial of TTFields in mesothelioma is registered on ClinicalTrials.gov as of March 2026.

This regulatory standstill stands in sharp contrast to NovoCure's progress in other cancer indications. In February 2026 the FDA approved Optune Pax for locally advanced pancreatic cancer via the full PMA pathway, supported by the phase 3 PANOVA-3 randomized controlled trial. Combined with the 2024 PMA approval of Optune Lua in metastatic NSCLC (LUNAR trial) and the original PMA approvals in glioblastoma (EF-11, EF-14), mesothelioma is now the only HDE indication remaining in NovoCure's U.S. portfolio — a function of the absence of a randomized mesothelioma trial, not a regulatory barrier per se.

The regulatory implications matter for patients and payers:

• The HDE pathway requires only a demonstration of probable benefit, not the demonstrated effectiveness standard required for PMA approval
• The FDA's own approval document for the NovoTTF-100L noted that "in the absence of a control group, statistical significance was not determined" and "the effectiveness of this device for this use has not been demonstrated"
• This evidentiary distinction is the primary reason some private insurers continue to classify TTFields for mesothelioma as investigational despite eight years of FDA approval (see Insurance and Financial Assistance below)

TTFields Regulatory Approvals Across Cancer Types

Indication	Year	Pathway	Pivotal Trial
Recurrent glioblastoma	2011	PMA	EF-11
Newly diagnosed glioblastoma	2015	PMA	EF-14
Malignant pleural mesothelioma	2019	HDE	STELLAR
Metastatic NSCLC (post-platinum)	2024	PMA	LUNAR
Locally advanced pancreatic cancer (Optune Pax)	Feb 2026	PMA	PANOVA-3

TTFields also received Conformité Européenne (CE) certification in Europe based on STELLAR results. Globally, more than 40,000 patients have been treated with TTFields across all four approved indications. The 2026 PMA approval of Optune Pax for pancreatic cancer (PANOVA-3 phase 3 RCT) reinforces by contrast that mesothelioma is now the only HDE indication in the TTFields portfolio — every other approved indication has cleared the higher PMA evidentiary standard via a randomized trial.

What Is the Treatment Protocol for TTFields Therapy?

First-Line Treatment Regimen

TTFields is approved for first-line use in combination with pemetrexed and platinum-based chemotherapy. The standard treatment protocol involves three phases:

Phase 1 — Concurrent Therapy: Continuous TTFields at 150 kHz (≥18 hours/day) delivered by two pairs of transducer arrays placed on the patient's torso, combined with up to 6 cycles of pemetrexed (500 mg/m²) plus cisplatin (75 mg/m²) or carboplatin, administered every 3 weeks.

Phase 2 — Maintenance: After completing chemotherapy, patients continue TTFields therapy alone as maintenance until disease progression, unacceptable toxicity, or patient/physician decision to stop.

In the STELLAR trial, patients received a median of 8 TTFields treatment cycles (range 2–41) and a median of 6 chemotherapy cycles. Among patients who progressed, 44 (56%) received post-study therapy, primarily second-line chemotherapy or pemetrexed rechallenge.

Contraindications

TTFields therapy is contraindicated in patients with:

• Implanted electronic medical devices (pacemakers, defibrillators)
• Known sensitivity to conductive gels (ECG or TENS-type)
• Requirement for supplemental oxygen
• Pregnancy (reproductive-age patients must use effective contraception)

Combination with Immunotherapy

Although no published clinical trial has specifically combined TTFields with immune checkpoint inhibitors in mesothelioma, preclinical evidence strongly supports this approach. Studies in mouse models demonstrated that concurrent TTFields with anti-PD-1 therapy significantly decreased tumor volume compared to either modality alone, with increased tumor-infiltrating lymphocytes. TTFields upregulate PD-L1 expression and promote conversion of the tumor microenvironment from immunologically "cold" to "hot." The LUNAR trial for NSCLC demonstrated that TTFields plus an immune checkpoint inhibitor yielded dramatic survival improvement over immunotherapy alone (19.0 vs 10.8 months), providing a strong rationale for investigating this combination in mesothelioma.

What Are the Side Effects of TTFields?

Dermatologic Adverse Events

The primary and essentially only adverse event attributable to TTFields is localized skin irritation beneath the transducer arrays. Based on STELLAR and a meta-analysis of four torso-based TTFields studies (N=192):

Adverse Event	Incidence
Any dermatologic adverse event	58%
Grade 1-2 dermatitis	53%
Grade 3-4 dermatologic events	6%
Grade 1-2 pruritus	9%
Device-related treatment discontinuation	5% (STELLAR)

Skin adverse events are principally caused by contact between the skin and array components (adhesive tape, hydrogel-covered ceramic discs) rather than by the electric fields themselves.

Prevention and Management

Key risk factors for skin adverse events include age, array contact with surgical scars, history of contact dermatitis, excessive sweating, prior radiation exposure, and use of high-dose systemic corticosteroids. Recommended prevention strategies include:

• Regular skin inspection during array changes
• Skin moisturization with mild, non-petroleum products compatible with TTFields therapy
• Adequate skin shaving and cleansing before array application
• Array position shifting (1–2 cm) at each replacement
• Beginning prophylaxis early (skin adverse events may develop in the first month)

For established skin events, early intervention is recommended. Mild dermatitis responds to topical high-potency corticosteroids, calcineurin inhibitors, or phosphodiesterase 4 inhibitors. Contact dermatitis requires isolation of affected skin from adhesives and topical or oral antibiotics if secondary infection develops.

Systemic Safety

TTFields therapy produces no systemic side effects. Animal studies and clinical experience have shown no evidence of cardiac toxicity. The device includes thermistors in each array that continuously monitor skin temperature, automatically shutting off if temperature exceeds 41°C. The LUNAR trial (N=133 TTFields-treated NSCLC patients) confirmed similar safety findings — only 6% reported a grade 3 TTFields-related adverse event, with no deaths attributed to the device.

How Does TTFields Compare to Other Mesothelioma Treatments?

TTFields occupies a unique position in the mesothelioma treatment landscape as a non-invasive, device-based therapy that can be combined with standard chemotherapy without adding systemic toxicity.

Cross-Indication TTFields Comparison

Cancer Type	Device	Frequency	Trial Phase	N	Median OS
Newly diagnosed GBM	Optune	200 kHz	Phase 3 (RCT)	695	20.9 months
Recurrent GBM	Optune	200 kHz	Phase 3 (RCT)	237	6.6 months
Unresectable MPM	Optune Lua	150 kHz	Phase 2 (single-arm)	80	18.2 months
Metastatic NSCLC	Optune Lua	150 kHz	Phase 3 (RCT)	276	13.2 months

The key difference for mesothelioma is the lack of a randomized controlled trial, unlike both GBM and NSCLC indications where phase 3 RCTs established a significant survival benefit.

Dose-Response Relationship

While limited data exist specifically for mesothelioma, the relationship between TTFields usage time and outcomes has been robustly demonstrated in glioblastoma research:

• In EF-11 (recurrent GBM): Patients using TTFields ≥18 hours/day had median OS of 7.7 months versus 4.5 months for fewer than 18 hours (p=0.04)
• In EF-14 (newly diagnosed GBM): A threshold of 50% usage was needed for improved PFS and OS; patients with greater than 90% usage showed median OS of 25 months and 5-year survival of 29%
• In PRiDe registry: Median OS was 13.5 months with ≥75% daily compliance versus 4.0 months with less than 75%

These data strongly support encouraging mesothelioma patients to maximize daily TTFields usage for optimal therapeutic benefit.

What Is the Cost of TTFields Therapy?

Device Pricing

The estimated cost of TTFields therapy is approximately $21,000 per month, based on published data primarily from the glioblastoma indication. This covers equipment rental, replacement arrays and supplies, and ongoing device support. In the STELLAR trial, patients received a median of 8 treatment cycles (approximately 5.5 months of continuous use), implying a typical total treatment cost in the range of $115,000 to $170,000 before insurance.

Insurance and Financial Assistance

Coverage for TTFields therapy in mesothelioma is materially less consistent than coverage for the glioblastoma indications, and the underlying reason traces back to the Humanitarian Device Exemption pathway rather than to the device or evidence per se.

The HDE pathway requires only a demonstration of probable benefit to a small population (fewer than 8,000 U.S. patients per year), whereas the Premarket Approval (PMA) pathway requires demonstrated effectiveness typically established through a phase 3 randomized controlled trial. Optune Lua's mesothelioma indication is the only TTFields indication still under HDE — its glioblastoma, NSCLC, and (as of February 2026) pancreatic cancer indications were all approved via PMA following randomized trials. Some payers anchor their medical necessity policies to the PMA standard and treat HDE-approved indications as "investigational" for that reason — even when the device is FDA-approved and clinically available.

Practical 2026 coverage realities:

• Medicare: Medicare covers TTFields therapy for glioblastoma at the national level; for mesothelioma specifically, coverage decisions are made by the regional Medicare Administrative Contractor (MAC) and can vary by jurisdiction. Patients should request a written coverage determination before initiating therapy
• Private Insurance: Most private insurers require prior authorization. A subset of plans classify TTFields for mesothelioma as investigational, citing the HDE pathway and the lack of phase 3 randomized data. Appeals citing FDA approval status, the STELLAR trial results, and the FDA-approved label often succeed but can take weeks to months
• NovoCure Patient Support: NovoCure operates a patient access program that assists with prior authorization, appeals, and financial assistance for qualifying patients based on income and insurance status
• Mesothelioma legal claims: Patients pursuing asbestos trust fund claims or civil litigation may recover medical expenses for TTFields therapy as part of damages, even when private insurance denies coverage. This is a meaningful financial pathway for patients facing investigational classification by their insurer

International Access

TTFields therapy for mesothelioma is commercially available in the United States (under HDE) and in Europe (CE mark). More than 110 U.S. hospitals are certified to offer TTFields for MPM. Reimbursement varies internationally, with the therapy covered in Austria, Czechia, France, Germany, Israel, Japan, Spain, Sweden, and Switzerland across approved indications.

Cost-Effectiveness

Published cost-effectiveness analyses for TTFields exist primarily for NSCLC using LUNAR trial data. An analysis estimated an incremental cost-effectiveness ratio (ICER) of $89,808 per quality-adjusted life year (QALY) for TTFields plus an immune checkpoint inhibitor or docetaxel versus those agents alone, falling within standard U.S. willingness-to-pay thresholds. No published cost-effectiveness analysis specific to mesothelioma was identified as of early 2026.

What Do Current Guidelines Say About TTFields?

NCCN Guidelines

The NCCN Clinical Practice Guidelines for Malignant Pleural Mesothelioma Version 2.2025 do not reference TTFields therapy. This omission likely reflects the single-arm phase 2 evidence base and HDE (rather than PMA) regulatory status.

ASCO Guidelines (2025 Update)

The ASCO Treatment of Pleural Mesothelioma guideline update (published in early 2025, the first update since 2018) focuses on surgical cytoreduction, immunotherapy (nivolumab plus ipilimumab; pembrolizumab plus chemotherapy), chemotherapy, pathology, and germline testing. TTFields is not prominently featured in the ASCO guideline recommendations.

European Guidelines

The Onkopedia guidelines (Germany) include TTFields as a treatment option for pleural mesothelioma, noting the 150 kHz frequency and combination with chemotherapy. The CE certification in Europe has supported inclusion in some European treatment algorithms.

NCI PDQ Summary

The NCI Physician Data Query (PDQ) mesothelioma treatment summary lists surgery, radiation, chemotherapy, immunotherapy, and targeted therapy, but does not specifically feature TTFields in its standard treatment sections.

Understanding the Guideline Gap

The absence of TTFields from NCCN and ASCO guidelines reflects the current evidence standard in oncology, where phase 3 randomized data typically underpin Category 1 recommendations. TTFields' inclusion in clinical practice is supported by FDA HDE approval but not by the randomized controlled trial data that guidelines committees generally require for strong endorsements. Independent reviewers have called for a randomized phase 3 study as "paramount" to establishing TTFields' true added benefit in mesothelioma.

As of early 2026, the position remains static: neither NCCN nor ASCO has elevated TTFields in their mesothelioma guidance, NovoCure has not announced a phase 3 randomized mesothelioma trial, and the comprehensive 2025 review by Ceresoli and Gianoncelli — published in Current Treatment Options in Oncology (PMID: 40266436) — summarizes the complete evidence base without reporting any new STELLAR survival analyses beyond the 2019 Lancet Oncology publication. The TIGER Meso real-world registry (described below) is the primary source of new TTFields-mesothelioma data being generated in 2025–2026.

What Clinical Trials Are Currently Underway?

TIGER Meso (NCT05538806)

TIGER Meso is the principal ongoing TTFields study in mesothelioma as of 2026.

• Design: Post-authorization, prospective, observational, real-world study — not an interventional trial and not a randomized comparison
• Sponsor: NovoCure Ltd.
• Principal Investigator: Giovanni Luca Ceresoli (Humanitas Gavazzeni Hospital, Bergamo, Italy)
• Estimated Enrollment: Approximately 198 patients across 23 centers
• Study Start: September 6, 2022
• Latest Status Update: August 18, 2025 (study ongoing and recruiting as of early 2026)
• Purpose: Collect real-life data on TTFields use in routine clinical care for pleural mesothelioma, including potential combinations with immunotherapy, modern chemotherapy regimens, and other systemic agents
• Limitation: TIGER Meso does not include a randomized comparator arm. It is designed to generate post-market observational data rather than confirmatory efficacy evidence

TIGER Meso results are expected to provide insight on real-world device compliance, tolerability, and patient outcomes in a broader population than the 80-patient STELLAR cohort. Because the study captures concurrent immunotherapy use, it may also offer the first multi-patient signal on TTFields plus checkpoint-inhibitor combinations in mesothelioma — a combination supported by strong preclinical rationale but not yet tested in a dedicated randomized trial.

TTFields Plus Immunotherapy

As of March 2026, no dedicated randomized trial combining TTFields with checkpoint inhibitors specifically in mesothelioma has been registered. However, the dramatic results from the LUNAR trial in NSCLC — where TTFields plus an immune checkpoint inhibitor yielded median OS of 19.0 months versus 10.8 months for immunotherapy alone — provide a strong scientific rationale for investigating this combination in mesothelioma.

Phase 3 Mesothelioma Trial

As of March 2026, no phase 3 randomized mesothelioma trial for TTFields has been registered on ClinicalTrials.gov. Independent reviewers have called for such a study as essential to establishing the true clinical benefit of TTFields in this disease.

Next-Generation Devices

NovoCure continues to improve the TTFields platform with smaller, lighter devices and more flexible array designs. The second-generation NovoTTF-200T is substantially smaller (1.2 kg versus 2.7 kg) with improved digital technology and more flexible ITE arrays designed to increase patient comfort and compliance.

What Is the Patient Experience Like?

Daily Living with TTFields

The Optune Lua device is designed to be as minimally disruptive to daily life as possible:

• Portability: The second-generation device weighs only 1.2 kg and can be carried in a shoulder bag or backpack, enabling patients to maintain most normal activities
• Showering: Arrays must be removed for showering and replaced with new arrays afterward
• Sleep: The device can be connected to an external power supply overnight, eliminating the need to change batteries during sleep
• Travel: Patients can travel with the device but should carry extra batteries (each lasting approximately one hour) for periods away from power sources
• Work: Patients can generally continue working while wearing the device, as it operates silently and can be worn under clothing

Caregiver Support

Patients should ideally have at least one caregiver who can assist with removing and reapplying arrays and managing skin adverse events. Patient and caregiver education and training before starting TTFields therapy are essential components of treatment. NovoCure Device Support Specialists provide technical training, education, and ongoing support to both patients and caregivers.

Quality of Life Considerations

In the STELLAR trial, quality of life was assessed using ECOG performance status and a visual analog scale for cancer-related pain until disease progression. No validated quality-of-life instrument results (such as the EORTC QLQ-C30) from STELLAR have been published specifically for mesothelioma. In GBM studies (EF-14), TTFields did not significantly worsen quality of life compared to temozolomide alone, except for a higher incidence of itchy skin — suggesting that the therapy is generally well-tolerated.

Historical Development of TTFields Technology

Year	Milestone
Late 1990s	Prof. Yoram Palti (Technion, Israel) begins exploring electric fields as cancer treatment
2000	NovoCure founded; preclinical research lab established
2003	First patient treated with TTFields in clinical trial (Switzerland)
2011	First FDA approval: recurrent glioblastoma (PMA)
Feb 2015	STELLAR trial begins enrolling mesothelioma patients
2015	Second FDA approval: newly diagnosed GBM + temozolomide (PMA)
Mar 2017	STELLAR enrollment complete
May 2019	FDA HDE approval for mesothelioma (NovoTTF-100L)
2019	STELLAR results published in The Lancet Oncology (Ceresoli et al.)
Oct 2024	FDA PMA approval for metastatic NSCLC (LUNAR trial)
2025	Ceresoli & Gianoncelli comprehensive TTFields-mesothelioma review published

As of 2026, NovoCure is an international oncology company headquartered in Baar, Switzerland, with U.S. headquarters in Portsmouth, New Hampshire, and R&D facilities in Haifa, Israel. The company employs over 1,300 people and has treated more than 40,000 patients globally across all approved cancer indications.

Frequently Asked Questions

What is TTFields therapy for mesothelioma?

TTFields (Tumor Treating Fields) therapy uses alternating electric fields delivered through a wearable device called Optune Lua to disrupt cancer cell division. For mesothelioma, the device operates at 150 kHz and is worn continuously for at least 18 hours per day alongside standard chemotherapy. It received FDA approval in 2019 and was the first new mesothelioma treatment approved in over 15 years.

How effective is TTFields for mesothelioma?

In the landmark STELLAR trial, 80 patients treated with TTFields plus chemotherapy achieved a median overall survival of 18.2 months, compared to 12.1 months for chemotherapy alone (historical control). The 1-year survival rate was 62.2% and the 2-year survival rate was 41.9%. Patients with epithelioid mesothelioma had even better outcomes, with median survival reaching 21.2 months.

What are the side effects of TTFields?

The only side effects directly attributable to TTFields are skin reactions beneath the transducer arrays. About 53% of patients experience mild-to-moderate dermatitis, while serious skin reactions occur in approximately 6% of patients. Importantly, TTFields cause no systemic side effects — there is no nausea, hair loss, or immune suppression from the device itself.

How much does TTFields therapy cost?

TTFields therapy costs approximately $21,000 per month, covering device rental, replacement arrays, and support services. A typical treatment course (median 8 cycles) may total $115,000 to $170,000 before insurance. NovoCure offers financial assistance for qualifying patients, and insurance coverage varies by payer.

Is TTFields covered by insurance?

Insurance coverage for TTFields mesothelioma therapy varies. Medicare covers TTFields for glioblastoma, but mesothelioma-specific coverage depends on the regional carrier. Private insurance typically requires prior authorization, and some insurers consider TTFields investigational for mesothelioma given the HDE approval pathway. NovoCure assists patients with billing and insurance navigation.

Can TTFields be combined with immunotherapy?

While no clinical trial has specifically combined TTFields with checkpoint inhibitors in mesothelioma, preclinical evidence strongly supports this approach. TTFields upregulate PD-L1 expression and promote immunogenic cell death. The LUNAR trial for lung cancer showed dramatic survival benefits when combining TTFields with immunotherapy. Real-world observational data from the TIGER Meso study may provide additional insight.

Why isn't TTFields in the NCCN guidelines?

The NCCN guidelines for mesothelioma (Version 2.2025) do not reference TTFields, likely because the evidence comes from a single-arm phase 2 trial rather than a randomized phase 3 study. NCCN typically requires randomized controlled trial data for Category 1 recommendations. However, TTFields remains an FDA-approved treatment option available at certified centers.

Who is eligible for TTFields therapy?

TTFields therapy is approved for adults with unresectable, locally advanced or metastatic malignant pleural mesothelioma. Patients must not have implanted electronic medical devices (pacemakers, defibrillators), known sensitivity to conductive gels, or require supplemental oxygen. Treatment is initiated at certified centers where NovoCure support specialists provide training for patients and caregivers.

Get Help

Mesothelioma patients and families can connect with experienced legal and medical advocates:

• Danziger & De Llano provides free case evaluations and can connect families with specialized treatment centers — call (855) 699-5441
• Mesothelioma Lawyer Center offers resources on treatment options and legal rights
• Mesothelioma.net provides comprehensive information on TTFields and treatment options

Quick Statistics

• More than 40,000 patients worldwide have been treated with TTFields across all four approved cancer indications
• Real-world device compliance averaged 12.5 hours/day at a single U.S. center — below the 18-hour target — with hot climate and patient frailty cited as barriers
• TTFields therapy costs approximately $21,000 per month, with NovoCure financial assistance available for qualifying patients
• A typical STELLAR treatment course lasted 8 median cycles (range 2–41), with 6 cycles of concurrent chemotherapy
• The TIGER Meso observational study (NCT05538806) aims to enroll 198 patients at 23 centers to collect real-world TTFields data
• 56% of progressing patients (44 of 80) received post-study therapy, primarily second-line chemotherapy or pemetrexed rechallenge
• TTFields are commercially reimbursed in 9+ countries including Austria, France, Germany, Israel, Japan, and Switzerland
• NovoCure employs over 1,300 people globally with headquarters in Switzerland and R&D in Haifa, Israel
• Device treatment discontinuation due to skin adverse events occurred in only 5% of STELLAR patients
• In glioblastoma, patients with ≥90% daily compliance achieved 25-month median OS and 29% 5-year survival — underscoring the importance of maximizing wear time

Related Pages

• Pleurodesis — Procedure often used alongside mesothelioma management
• VATS and Thoracoscopic Procedures — Minimally invasive diagnostic and therapeutic approaches
• Pleurectomy/Decortication — Surgical treatment for mesothelioma
• Extrapleural Pneumonectomy — Radical surgical approach
• Understanding Your Diagnosis — Guide to the diagnostic process
• Pleural Mesothelioma — Overview of the most common mesothelioma type
• Asbestos Trust Fund Quick Reference — Compensation resources
• Veterans Mesothelioma Quick Reference — Military-specific information

Free, Confidential Case Evaluation Call (855) 699-5441 or visit dandell.com/contact-us No upfront fees • Experienced representation • National practice

⚠ Statute of Limitations Warning: Filing deadlines vary by state from 1-6 years from diagnosis. Texas allows 2 years from diagnosis or discovery. Contact an attorney immediately to preserve your rights.