A phase II open-label multicenter study of gefitinib in combination with irradiation followed by chemotherapy in patients with inoperable stage III non-small cell lung cancer

// Antonin Levy 1,2,3 , Etienne Bardet 4 , Benjamin Lacas 5,6 , Jean-Pierre Pignon 5,6 , Julien Adam 7 , Ludovic Lacroix 7 , Xavier Artignan 8,10 , Pierre Verrelle 9 and Cecile Le Pechoux 1 1 Department of Radiation Oncology, Gustave Roussy, Universite Paris-Saclay, Institut Thoracique d’Oncologie (IOT), Villejuif, France 2 INSERM U1030, Molecular Radiotherapy, Gustave Roussy, Universite Paris-Saclay, Villejuif, France 3 Univ Paris Sud, Universite Paris-Saclay, Le Kremlin-Bicetre, France 4 Department of Medical Oncology, Institut de Cancerologie de l’Ouest, Nantes, France 5 Gustave Roussy, Universite Paris-Saclay, Department of Biostatistics and Epidemiology, Villejuif, France 6 INSERM U1018, CESP, Universite Paris-Sud, Universite Paris-Saclay, Villejuif, France 7 Department of Medical Biology and Pathology, Translational Research Laboratory and Biobank (UMS3655 CNRS / US23 INSERM), INSERM Unit U981, Villejuif, France 8 Department of Radiation Oncology, University Hospital Grenoble, Grenoble, France 9 Department of Radiation Oncology, Centre Jean Perrin, Clermont-Ferrand, France 10 Department of Radiation Oncology, St Gregoire Hospital, St Gregoire, France Correspondence to: Cecile Le Pechoux, email: // Keywords : iressa, thoracic radiotherapy, lung cancer, phase II trial Received : July 06, 2016 Accepted : October 12, 2016 Published : October 18, 2016 Abstract Background: Gefitinib is an oral EGFR tyrosine kinase inhibitors which may act as a radiosensitizer. Patients and Methods: This phase II study evaluated the efficacy of gefitinib 250 mg once daily in combination with thoracic radiotherapy (66 Gy in 6.5 weeks, 2 Gy/day, 5 fractions/week) followed by consolidation chemotherapy (IV cisplatin and vinorelbine) as first line treatment in a population of unselected stage IIIB NSCLC patients according to EGFR mutation status. Results: Due to a low accrual rate in this study, the sample size ( n = 50) was not reached. Sixteen patients were included in four centers, 50% had adenocarcinoma and 75% were male. Genomic alterations (7 patients studied) retrieved TP53 mutation in 2 patients and no EGFR mutation. Four weeks after radiotherapy, 3 patients (19%) had a partial response, 6 (38%) had a stable disease, and 7 had a progression (44%). Median overall survival was 11 months and median progression-free survival was 5 months. At the time of the last contact, 5 patients (31%) were still alive . Main toxicities were gastrointestinal (81%), cutaneous (81%), general (56%), and respiratory (50%). There were 12>G3 adverse events in 7 (47%) patients, and there was one toxic-death during the concomitant period due to an interstitial pneumonitis. There were two possible adverse events-related deaths during the chemotherapy period (pulmonary embolism ( n = 1) and sudden death after the administration of the 3 rd course of chemotherapy ( n = 1)). Conclusion: The benefit of Gefitinib-RT could not be confirmed due to premature trial discontinuation. Further evaluation is required, especially in patients with EGFR mutated NSCLC.