Abstract CT201: Final results of Phase II STELLAR trial: TTFields with chemotherapy in unresectable malignant pleural mesothelioma
Authors: Ceresoli Giovanni Luca , Aerts Joachim , Madrzak Jaroslaw , Dziadziuszko Rafal , Ramlau Rodryg , Cedres Susana , Hiddinga Birgitta , VanMeerbeeck Jan , Mencoboni Manlio , Planchard David , Chella Antonio , Crino Lucio , Krzakowski Maciej , Grosso Federica 
Published: August 2019

Background Tumor Treating Fields (TTFields) are an anti-mitotic, regional treatment modality, utilizing low intensity alternating electric fields delivered non-invasively to the tumor using a portable device. In-vitro, human mesothelioma cells were highly susceptible to TTFields. TTFields plus chemotherapy have significantly extended survival in glioblastoma.

Method Patients (n= 80) with unresectable, previously untreated mesothelioma were treated with continuous 150 kHz TTFields (&gt;18h/day) in combination with pemetrexed and cisplatin or carboplatin. Inclusion criteria: ECOG PS 0-1, pathologically proven mesothelioma and at least one measurable lesion per modified RECIST criteria. The primary endpoint was overall survival (OS) and secondary endpoints were response rate, progression free survival (PFS) and toxicity. EOCG status and cancer-related pain were assessed until disease progression using a visual analog scale. This prospective, single arm study assumed an historical control with a median survival of 12.1 months (Vogelzang, JCO. 2003). The sample size provides 80% power with a two-sided alpha of 0.05 to detect an increase in median OS of 5.5 months.

Result All 80 patients had a minimum follow up of 12 months. Median age was 67 (range 27-78), 84% were male and 44% (35 patients) had an ECOG PS of 1. 66% (53 patients) had epithelioid histology, similar to the Vogelzang study. Median OS was 18.2 months (95% CI 12.1-25.8) versus 12.1 months in the historical control. The 1-year survival rate was 62.2% (95% CI 50.3-72.0). Median OS for epithelioid patients was 21.2 months (95% CI 13.2-25.8). Clinical benefit (PR+SD) was seen in 97.2% of patients. ECOG score was stable during the first year of follow up. Compliance with TTFields was 68% (16.3 hours/day) during the first 3 months of therapy. 63% (50 patients) received carboplatin. Median time to deterioration in performance status was 13.1 months. Average pain score was lower compared to baseline during the first 7 months of treatment and higher later with a median time to a clinical significant 33% increase in pain of 8.4 months. No device-related serious adverse events (AEs) were reported. Expected TTFields-related dermatitis was reported in 46% (37 patients). Four patients (5%) had grade 3 dermatitis. Grade 3-4 systemic AEs were reported in &gt;3% of patients: hematological AEs (15%) and fatigue (4%).

Conclusion The study met its primary endpoint of significant extension of survival in previously untreated mesothelioma patients. Secondary efficacy endpoints were also improved compared to historical control. The study demonstrated no safety concerns for TTFields plus standard chemotherapy to the thorax. The use of the TTFields was not associated with a decrease in performance status or an increase in pain. TTFields in combination with chemotherapy are efficacious in malignant pleural mesothelioma vs chemotherapy alone in historical data.

Citation Format: Giovanni Luca Ceresoli, Joachim Aerts, Jaroslaw Madrzak, Rafal Dziadziuszko, Rodryg Ramlau, Susana Cedres, Birgitta Hiddinga, Jan VanMeerbeeck, Manlio Mencoboni, David Planchard, Antonio Chella, Lucio Crino, Maciej Krzakowski, Federica Grosso. Final results of Phase II STELLAR trial: TTFields with chemotherapy in unresectable malignant pleural mesothelioma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr CT201.