STELLAR – Final results of a phase 2 trial of TTFields with chemotherapy for first line treatment of pleural mesothelioma

Date 20 October 2018
Event ESMO 2018 Congress
Session Poster display session: Biomarkers, Gynaecological cancers, Haematological malignancies, Immunotherapy of cancer, New diagnostic tools, NSCLC - early stage, locally advanced & metastatic, SCLC, Thoracic malignancies, Translational research
Topics Anticancer Agents
Mesothelioma
Presenter Federica Grosso
Citation Annals of Oncology (2018) 29 (suppl_8): viii641-viii644. 10.1093/annonc/mdy301
Authors F. Grosso1, J.G. Aerts2, J. Madrzak3, R. Dziadziuszko3, R. Ramlau4, S. Cedres5, B. Hiddinga6, J.P. van Meerbeeck6, M. Mencoboni7, D. Planchard8, A. Chella9, L. Crino10, M.J. Krzakowski11, G.L. Ceresoli12
  • 1Oncology, SS Antonio e Biagio Hospital, Department of Oncology, Via Venezia 16, 15121 - Alessandria/IT
  • 2Oncology, Erasmus University Medical Center, 3015 CE - Rotterdam/NL
  • 3Oncology, Medical University of Gdansk Clinical Hospital, Gdansk/PL
  • 4Oncology, Medical University of Poznan, Poznan/PL
  • 5Oncology, Vall d’Hebron University Hospital, Barcelona/ES
  • 6Oncology, Antwerp University Hospital, Antwerp/BE
  • 7Oncology, Ospedale Villa Scassi, 16149 - Genova/IT
  • 8Oncology, Institut Gustave Roussy, 94800 - Villejuif/FR
  • 9Oncology, Cisanello University hospital Pisa, 56124 - Pisa/IT
  • 10Oncology, Ospedale S. Maria della Misericordia, 06156 - Perugia/IT
  • 11Department Of Lung & Thoracic Tumours, The Maria Sklodowska-Curie Memorial Institute and Oncology Centre, 02-781 - Warsaw/PL
  • 12Oncology, Humanitas Gavazzeni, 24125 - Bergamo/IT

Abstract

Background

Tumor Treating Fields (TTFields) are an anti-mitotic, regional treatment modality, using low intensity alternating electric fields delivered non-invasively to the tumor using a portable, medical device. In vitro, human mesothelioma cells were highly susceptible to TTFields. TTFields have been shown to extend survival of patients with glioblastoma when added to chemotherapy.

Methods

The trial accrued 80 patients with unresectable, untreated mesothelioma. Patients were treated with continuous 150 kHz TTFields in combination with pemetrexed and platinum. Inclusion criteria included ECOG 0-1 and at least one measurable lesion according to modified RECIST. Patients were followed q3w (CT scan q6w) until disease progression. The primary endpoint was overall survival (OS). This single arm study assumed historical control with a median survival of 12.1 months (Vogelzang et al. 2003). The sample size provided 80% power with a two-sided alpha of 0.05 to detect an increase in median OS of 5.5 months.

Results

All patients had a minimum follow up of 12 months. Median age was 67 (range 27-78), 84% were male and 56% smokers. 16% (13 patients) had metastatic disease and 44% (35 patients) had an ECOG PS of 1. 66% (53 patients) had epithelioid histology. Compliance with TTFields was 68% (16.3 hours/day) during the first 3 months of therapy. Median OS was 18.2 months (95% CI 12.1-25.8) compared to 12.1 months in historical controls. Median PFS was 7.6 months (95% CI 6.7-8.6) compared to 5.7 months in historical controls. Partial responses were seen in 40.3% of patients and clinical benefit (PR+SD) was seen in 97.2% of patients. No device-related serious adverse events (AEs) were reported. Expected TTFields-related dermatitis was reported in 46% (37 patients). Only 4 patients (5%) had grade 3 dermatitis.

Conclusions

The study met its primary endpoint of significant extension of survival for previously untreated mesothelioma patients. Secondary efficacy endpoints were also improved compared to historical control. The study demonstrated no safety concerns for the combination of TTFields to the thorax with chemotherapy. These results support the addition of TTFields to chemotherapy in the first-line treatment of malignant pleural mesothelioma.

Clinical trial identification

NCT02397928.

Legal entity responsible for the study

Novocure.

Funding

Novocure.

Editorial Acknowledgement

Disclosure

J.G. Aerts: Advisory boards: BMS, MSD, Roche, AstraZeneca, Eli Lilly, Boehringer Ingelheim, Amphera; Stock owner: Amphera. R. Ramlau: Consultant: Novocure. All other authors have declared no conflicts of interest.