On May 23, 2019, the U.S. Food and Drug Administration approved the NovoTTF-100L System for the treatment of unresectable malignant pleural mesothelioma. The device, later marketed as Optune Lua, represented the first new FDA-approved treatment for mesothelioma in more than 15 years, breaking a long drought since pemetrexed (Alimta) was approved in 2004.
What Is the NovoTTF-100L/Optune Lua?
The NovoTTF-100L System is a wearable medical device that delivers Tumor Treating Fields (TTFields), low-intensity, alternating electric fields, directly to the region of the tumor.
How Tumor Treating Fields Work
TTFields work differently from chemotherapy and radiation:
- Targeted Disruption: Electric fields are tuned to specific frequencies that interfere with cancer cell division
- Selective Effect: Normal cells divide slowly and are less affected; rapidly dividing cancer cells are disrupted
- Non-Invasive: The treatment is delivered through electrode arrays (transducer arrays) worn on the torso
- Continuous Treatment: Patients wear the device for at least 18 hours per day
The electric fields disrupt the mitotic spindle formation during cell division, preventing cancer cells from successfully completing mitosis.
The STELLAR Trial Results
FDA approval was based on the STELLAR trial, which studied TTFields combined with chemotherapy in previously untreated mesothelioma patients.
Study Design
- Patients: 80 with unresectable, previously untreated malignant pleural mesothelioma
- Treatment: NovoTTF-100L plus pemetrexed and platinum-based chemotherapy
- Primary Endpoint: Overall survival
Efficacy Results
| Outcome | Result |
|---|---|
| Median overall survival | 18.2 months |
| 1-year survival rate | 62% |
| Disease control rate | 97% |
| Partial response rate | 40% |
| Stable disease rate | 57% |
| Median progression-free survival | 7.6 months |
Results by Cell Type
The trial showed survival benefits across mesothelioma subtypes:
| Cell Type | Median Survival |
|---|---|
| Epithelioid (n=53) | 21.2 months |
| Non-epithelioid (n=21) | 12.1 months |
The 21.2-month survival for epithelioid patients was particularly encouraging, exceeding historical data for chemotherapy alone.
Comparison to Standard Treatment
Before this approval, pemetrexed plus cisplatin had been the only FDA-approved first-line treatment since 2004. Historical outcomes with chemotherapy alone:
| Treatment | Median Survival | Trial |
|---|---|---|
| Chemotherapy alone | 12-14 months | Historical controls |
| TTFields + chemotherapy | 18.2 months | STELLAR |
The addition of TTFields appeared to extend median survival by approximately 4-6 months compared to chemotherapy alone.
FDA Approval Details
Humanitarian Device Exemption
The NovoTTF-100L was approved under the FDA’s Humanitarian Device Exemption (HDE) program, which is designed for devices that treat conditions affecting fewer than 8,000 patients per year in the United States. Mesothelioma, with approximately 3,000 new cases annually, qualifies as a rare disease.
Approved Indication
The device is approved for:
- Adult patients with unresectable malignant pleural mesothelioma
- Locally advanced or metastatic disease
- Used concurrently with pemetrexed and platinum-based chemotherapy
- First-line treatment (patients who have not received prior systemic therapy)
Practical Considerations
Wearing the Device
Patients must wear the device for at least 18 hours daily for maximum benefit. The system includes:
- Transducer arrays placed on the torso
- A portable battery pack
- A device driver unit
Side Effects
The most common side effect is skin irritation under the electrode arrays, which can usually be managed with electrode repositioning and topical treatments.
Cost and Access
The treatment is expensive, with costs exceeding $20,000 per month. Insurance coverage varies, and patients often need to work with their care team and Novocure’s patient assistance programs to navigate access.
Clinical data shows treatment benefit correlates with wearing time. Patients who wore the device for at least 18 hours daily achieved the survival outcomes reported in STELLAR. Work with your care team to optimize compliance despite the practical challenges.
Significance for Mesothelioma Treatment
The Optune Lua approval marked several milestones:
- End of a 15-Year Drought: No new mesothelioma treatments had been approved since 2004
- First Medical Device: Previous treatments were drugs; this was the first device approval
- Novel Mechanism: TTFields work differently from chemotherapy, potentially offering benefit without typical chemotherapy side effects
- Foundation for Future Approvals: The approval demonstrated FDA’s willingness to approve new mesothelioma treatments, setting the stage for the Opdivo+Yervoy approval in 2020
What Came After
The Optune Lua approval proved to be the beginning of a new era in mesothelioma treatment:
- October 2020: FDA approved nivolumab plus ipilimumab (Opdivo+Yervoy), the first immunotherapy for mesothelioma
- Ongoing trials: Multiple combinations of TTFields with immunotherapy are being studied
How does Optune Lua work?▼
Optune Lua delivers Tumor Treating Fields (TTFields)—low-intensity, alternating electric fields—through electrode arrays worn on the torso. These fields are tuned to frequencies that disrupt cancer cell division by interfering with mitotic spindle formation. Normal cells, which divide slowly, are less affected than rapidly dividing cancer cells.
Who is eligible for Optune Lua?▼
The device is FDA-approved for adult patients with unresectable, locally advanced or metastatic malignant pleural mesothelioma who have not received prior systemic therapy. It must be used concurrently with pemetrexed and platinum-based chemotherapy as first-line treatment.
What were the STELLAR trial results?▼
The trial showed 18.2 months median overall survival with TTFields plus chemotherapy. For epithelioid patients specifically, median survival was 21.2 months. The disease control rate was 97%, and one-year survival was 62%. These results exceeded historical outcomes with chemotherapy alone.
What are the main side effects and challenges?▼
The most common side effect is skin irritation under the electrode arrays, usually manageable with repositioning and topical treatments. The main challenge is compliance—patients must wear the device at least 18 hours daily. Cost exceeds $20,000/month, though patient assistance programs exist.