Electrical Current Therapy Receives FDA Approval for Pleural Mesothelioma (Lung Lining Cancer)

The United States Food and Drug Administration (FDA) on 24 May 2019 authorized electric current therapy for unresectable, locally advanced or metastatic, malignant pleural mesothelioma(cancer of the lung lining) as first-line treatment in combination with pemetrexed plus platinum-based chemotherapy . This electrical treatment is called tumor treating fields (TTF).

The NovoTTF-100L System (Novocure), following the approval of pemetrexed in 2004, is the first malignant mesothelioma treatment approved by the FDA in 15 years.

For inoperable malignant pleural mesothelioma (lung lining cancer), adding a special electrical current treatment called tumor-treating fields (TTF) to standard chemotherapy was shown to significantly prolong survival and be safe. The results of STELLAR, a phase-2 clinical trial, were presented at the 2019 Multidisciplinary Thoracic Cancers Symposium. For patients with advanced mesothelioma, platinum (cisplatin or carboplatin) and pemetrexed doublet chemotherapy combined with low-intensity alternating electric currents produced a median overall survival of 18.2 months ; historical median survival for this group is known to be 12.1 months.

Pleural mesothelioma originates from the lung lining and is among rare cancers, but its incidence is increasing worldwide. Despite years of research and promising preliminary results of immunotherapies, the only approved regimen for mesothelioma is cisplatin and pemetrexed, presented 15 years ago by Vogelzang and colleagues; median overall survival with this treatment is only around 1 year.

Tumor-treating fields (TTF) is an antimitotic regional cancer treatment device that delivers low-intensity alternating electric currents to the tumor. These currents inhibit spindle formation during the metaphase stage of mitosisand therefore cell division. This treatment previously received FDA approval for treatment of the brain tumor GBM .

Laboratory studies had shown that human mesothelioma cells were highly sensitive to TTF waves at 150 kHZ and that their combination with chemotherapy had synergistic effects.

Details of the STELLAR study

• Patients received 6 cycles of platinum+pemetrexed chemotherapy alongside TTF for at least 18 hours daily.
• Patients whose cancer did not progress after this combination continued low-intensity electric current alone as maintenance treatment until disease progression, unacceptable toxicity (side effects) or death.
• Cancer burden was assessed every 6 weeks with abdominal and thoracic (chest) computed tomography scans.
• The primary endpoint the study aimed to measure was overall survival. Overall response rate, progression-free survival and safety were secondary endpoints.

Study results

• Patients’ median age was 67, and %84 were male.
• Histological subtypes were well represented: %66 of patients had epithelioid and %26 sarcomatoid/biphasic disease.
• Median overall survival was 18.2 months; compared with the 12.1-month historical control, this combination reduced the risk of death by %44.
• The 1-year overall survival rate was %62, and median overall survival in epithelioid patients alone was 21.2 months.
• Median progression-free survival was 7.6 months and overall response rate was %40.
• Treatment appeared well tolerated; most side effects were attributed to chemotherapy. A median of %68 of patients could use the device for at least 16 hours.
• The most commonly reported device-related side effect was skin toxicity (dermatitis at the transducer attachment site). A total of 4 patients (%5) had severe (grade 3) toxicity, which improved with corticosteroid cream and a short treatment break.