Giovanni L Ceresoli1, Joachim G Aerts2, Rafal Dziadziuszko3, Rodryg Ramlau4, Susana Cedres5, Jan P van Meerbeeck6, Manlio Mencoboni7, David Planchard8, Antonio Chella9, Lucio Crinò10, Maciej Krzakowski11, Jörn Rüssel12, Antonio Maconi13, Letizia Gianoncelli14, Federica Grosso15. 1. Department of Oncology, Cliniche Humanitas Gavazzeni, Bergamo, Italy. Electronic address: giovanni_luca.ceresoli@gavazzeni.it. 2. Erasmus Medical Center, Rotterdam, Netherlands. 3. Department of Oncology and Radiotherapy, Medical University of Gdansk, Gdansk, Poland. 4. Department of Oncology, University of Poznan, Poznan, Poland. 5. Medical Oncology, Vall d'Hebron Institute of Oncology, Vall d'Hebron University Hospital, Barcelona, Spain. 6. Department of Pulmonology and Thoracic Oncology, ERN-Lung, Antwerp University Hospital, Antwerp, Belgium. 7. SSD Oncologia, Ospedale Villa Scassi, ASL 3 Genovese, Genova, Italy. 8. Department of Thoracic Oncology, Institute Gustave Roussy, Villejuif, France. 9. Department of Oncology, Azienda Ospedaliero Universitaria Pisana, Pisa, Italy. 10. Medical Oncology Division, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori, IRCCS, Meldola, Italy. 11. Department of Lung Cancer and Chest Tumours, Maria Skłodowska-Curie Memorial Cancer Centre, Warsaw, Poland. 12. Department of Haematology and Oncology, University Hospital Halle (Saale), Halle (Saale), Germany. 13. Scientific Research and Development Department, Azienda Ospedaliera SS Antonio e Biagio e Cesare Arrigo, Alessandria, Italy. 14. Department of Oncology, Cliniche Humanitas Gavazzeni, Bergamo, Italy; Division of Thoracic Oncology, European Institute of Oncology, IRCCS, Milan, Italy. 15. Mesothelioma Unit, Azienda Ospedaliera SS Antonio e Biagio e Cesare Arrigo, Alessandria, Italy.
Abstract
BACKGROUND: Tumour Treating Fields (TTFields) are a regional, antimitotic treatment for solid tumours, which is based on the delivery of low-intensity alternating electric fields. The aim of the STELLAR study was to test the activity of TTFields delivered to the thorax in combination with systemic chemotherapy for the front-line treatment of patients with unresectable malignant pleural mesothelioma. METHODS: STELLAR was a prospective, single-arm, phase 2 trial done at 12 European academic and non-academic sites (five in Italy, three in Poland, one in France, one in Belgium, one in Spain, and one in the Netherlands) for treatment-naive patients with histologically confirmed unresectable malignant pleural mesothelioma. Patients were aged at least 18 years, had an Eastern Cooperative Oncology Group performance status of 0-1, and at least one measurable or evaluable lesion according to modified Response Evaluation Criteria in Solid Tumors for mesothelioma. Patients received continuous TTFields at a frequency of 150 kHz to the thorax and concomitant chemotherapy with intravenous pemetrexed (500 mg/m2 on day 1) plus intravenous platinum (either cisplatin 75 mg/m2 on day 1 or carboplatin area under the curve 5 on day 1) every 21 days for up to six cycles. Patients not progressing after completion of chemotherapy received TTFields as maintenance treatment until progression, patient or physician decision, or unacceptable toxic effects. The primary endpoint of the trial was overall survival. Survival analyses were done in the intention-to-treat population, and safety analyses were done in all patients who received at least 1 day of TTFields treatment. This trial is registered with ClinicalTrials.gov, NCT02397928. FINDINGS: Between Feb 9, 2015 and March 21, 2017, 80 patients were enrolled in the study. Median follow-up was 12·5 months (IQR 7·4-16·6). Median overall survival was 18·2 months (95% CI 12·1-25·8). The most common grade 3 or worse adverse events were anaemia (nine [11%] patients), neutropenia (seven [9%]), and thrombocytopenia (four [5%]). Skin reaction was the only adverse event associated with TTFields and was reported as grade 1-2 in 53 (66%) patients, and as grade 3 in four (5%) patients. No treatment-related deaths were observed. INTERPRETATION: The trial showed encouraging overall survival results, with no increase in systemic toxicity. TTFields (150 kHz) delivered to the thorax concomitant with pemetrexed and platinum was an active and safe combination for front-line treatment of unresectable malignant pleural mesothelioma. Further investigation in a randomised trial is warranted. FUNDING: Novocure.
BACKGROUND: Tumour Treating Fields (TTFields) are a regional, antimitotic treatment for solid tumours, which is based on the delivery of low-intensity alternating electric fields. The aim of the STELLAR study was to test the activity of TTFields delivered to the thorax in combination with systemic chemotherapy for the front-line treatment of patients with unresectable malignant pleural mesothelioma. METHODS:STELLAR was a prospective, single-arm, phase 2 trial done at 12 European academic and non-academic sites (five in Italy, three in Poland, one in France, one in Belgium, one in Spain, and one in the Netherlands) for treatment-naive patients with histologically confirmed unresectable malignant pleural mesothelioma. Patients were aged at least 18 years, had an Eastern Cooperative Oncology Group performance status of 0-1, and at least one measurable or evaluable lesion according to modified Response Evaluation Criteria in Solid Tumors for mesothelioma. Patients received continuous TTFields at a frequency of 150 kHz to the thorax and concomitant chemotherapy with intravenous pemetrexed (500 mg/m2 on day 1) plus intravenous platinum (either cisplatin 75 mg/m2 on day 1 or carboplatin area under the curve 5 on day 1) every 21 days for up to six cycles. Patients not progressing after completion of chemotherapy received TTFields as maintenance treatment until progression, patient or physician decision, or unacceptable toxic effects. The primary endpoint of the trial was overall survival. Survival analyses were done in the intention-to-treat population, and safety analyses were done in all patients who received at least 1 day of TTFields treatment. This trial is registered with ClinicalTrials.gov, NCT02397928. FINDINGS: Between Feb 9, 2015 and March 21, 2017, 80 patients were enrolled in the study. Median follow-up was 12·5 months (IQR 7·4-16·6). Median overall survival was 18·2 months (95% CI 12·1-25·8). The most common grade 3 or worse adverse events were anaemia (nine [11%] patients), neutropenia (seven [9%]), and thrombocytopenia (four [5%]). Skin reaction was the only adverse event associated with TTFields and was reported as grade 1-2 in 53 (66%) patients, and as grade 3 in four (5%) patients. No treatment-related deaths were observed. INTERPRETATION: The trial showed encouraging overall survival results, with no increase in systemic toxicity. TTFields (150 kHz) delivered to the thorax concomitant with pemetrexed and platinum was an active and safe combination for front-line treatment of unresectable malignant pleural mesothelioma. Further investigation in a randomised trial is warranted. FUNDING: Novocure.
Authors: Rea Ravin; Teddy X Cai; Randall H Pursley; Marcial Garmendia-Cedillos; Tom Pohida; Raisa Z Freidlin; Herui Wang; Zhengping Zhuang; Amber J Giles; Nathan H Williamson; Mark R Gilbert; Peter J Basser Journal: Biophys J Date: 2020-11-13 Impact factor: 4.033
Authors: Alondra A Aguilar; Michelle C Ho; Edwin Chang; Kristen W Carlson; Arutselvan Natarajan; Tal Marciano; Ze'ev Bomzon; Chirag B Patel Journal: Cancers (Basel) Date: 2021-05-10 Impact factor: 6.639