Marina Chiara Garassino1, Alain Jonathan Gelibter2, Francesco Grossi3, Rita Chiari4, Hector Soto Parra5, Stefano Cascinu6, Francesco Cognetti7, Daniele Turci8, Livio Blasi9, Carmelo Bengala10, Enrico Mini11, Editta Baldini12, Silvia Quadrini13, Giovanni Luca Ceresoli14, Paola Antonelli15, Enrico Vasile16, Carmine Pinto17, Gianpiero Fasola18, Domenico Galetta19, Marianna Macerelli18, Diana Giannarelli7, Giuseppe Lo Russo20, Filippo de Marinis21. 1. Thoracic Oncology Unit, Medical Oncology Department, National Cancer Institute, Milan, Italy. 2. Oncology Unit, Umberto I Hospital, Sapienza University of Rome, Rome, Italy. 3. Lung Cancer Unit, San Martino Hospital, Genova, Italy. 4. Department of Engineering, University of Perugia, Perugia, Italy. 5. Department of Oncology, Vittorio Emanuele Hospital, Catania, Italy. 6. Department of Oncology/Haematology, University of Modena and Reggio Emilia, Modena, Italy. 7. Department of Oncology, Regina Elena National Cancer Institute, Rome, Italy. 8. Department of Oncology, Santa Maria delle Croci Hospital, Ravenna, Italy. 9. Department of Oncology, Palermo Hospital, Palermo, Italy. 10. Oncology Department, Misericordia Hospital, Grosseto, Italy. 11. Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy. 12. Department of Oncology, Lucca Hospital, Lucca, Italy. 13. Department of Oncology, Santissima Trinita' Hospital, Sora (Frosinone), Italy. 14. Department of Medical Oncology, Humanitas Gavezzeni Hospital, Bergamo, Italy. 15. Department of Oncology, Busto Arsizio Hospital, Varese, Italy. 16. Department of Oncology, Polo Oncologico, University Hospital of Pisa, Pisa, Italy. 17. Medical Oncology Unit, Clinical Cancer Centre, Santa Maria Nuova Hospital, Reggio Emilia, Italy. 18. Department of Oncology, University Hospital Santa Maria della Misericordia, Udine, Italy. 19. Medical Oncology Unit, Clinical Cancer Center Giovanni Paolo II, Bari, Italy. 20. Thoracic Oncology Unit, Medical Oncology Department, National Cancer Institute, Milan, Italy. Electronic address: giuseppe.lorusso@istitutotumori.mi.it. 21. Division of Thoracic Oncology, European Institute of Oncology, Milan, Italy.
Abstract
INTRODUCTION: Nivolumab is the first checkpoint inhibitor approved for the treatment of nonsquamous NSCLC. We report results from the nivolumab Italian expanded access program focusing on never-smokers and patients with EGFR-mutant nonsqamous NSCLC. METHODS: Nivolumab (3 mg/kg intravenously every 2 weeks) was administered upon physicians' request to patients who had relapsed after one or more prior systemic treatments for stage IIIB/IV nonsquamous NSCLC. Efficacy and safety were evaluated in patients who received at least one dose of nivolumab. RESULTS: Of 1588 patients with nonsquamous NSCLC, 305 (19.2%) were never-smokers. EGFR status was available for 1395 patients. Of the 102 patients (6.4%) with EGFR mutation-positive tumors, 51 (50%) were never-smokers. The objective response rate was significantly higher in patients with wild-type EGFR than patients with EGFR-mutant tumors (19.6% versus 8.8% [p = 0.007]), in former and current smokers than in never-smokers (21.5% versus 9.2% [p = 0.0001]), and in never-smokers with wild-type EGFR than in never-smokers with mutant EGFR (11.0% versus 1.9% [p = 0.04]). There was no significant difference in objective response rate between smokers with wild-type EGFR and smokers with mutant EGFR (22.0% versus 20.6%). There was no statistically significant difference in median progression-free survival or in median overall survival. The median overall survival times were 11 months in patients with EGFR wild-type tumors versus 8.3 months in patients with EGFR-mutant tumors, 11.6 months in smokers versus 10.0 months in never-smokers, 11.0 months in never-smokers with EGFR wild-type tumors versus 5.6 months in never-smokers with EGFR-mutant tumors, and 14.1 months in smokers with EGFR-mutant tumors versus 11.3 months in smokers with EGFR wild-type tumors. CONCLUSIONS: The data on the Italian expanded access program in populations with nonsquamous NSCLC suggest that subgroups of patients could benefit differently from nivolumab according to their EGFR mutational status and smoking habits. These results warrant further investigation.
INTRODUCTION:Nivolumab is the first checkpoint inhibitor approved for the treatment of nonsquamous NSCLC. We report results from the nivolumab Italian expanded access program focusing on never-smokers and patients with EGFR-mutant nonsqamous NSCLC. METHODS:Nivolumab (3 mg/kg intravenously every 2 weeks) was administered upon physicians' request to patients who had relapsed after one or more prior systemic treatments for stage IIIB/IV nonsquamous NSCLC. Efficacy and safety were evaluated in patients who received at least one dose of nivolumab. RESULTS: Of 1588 patients with nonsquamous NSCLC, 305 (19.2%) were never-smokers. EGFR status was available for 1395 patients. Of the 102 patients (6.4%) with EGFR mutation-positive tumors, 51 (50%) were never-smokers. The objective response rate was significantly higher in patients with wild-type EGFR than patients with EGFR-mutant tumors (19.6% versus 8.8% [p = 0.007]), in former and current smokers than in never-smokers (21.5% versus 9.2% [p = 0.0001]), and in never-smokers with wild-type EGFR than in never-smokers with mutant EGFR (11.0% versus 1.9% [p = 0.04]). There was no significant difference in objective response rate between smokers with wild-type EGFR and smokers with mutant EGFR (22.0% versus 20.6%). There was no statistically significant difference in median progression-free survival or in median overall survival. The median overall survival times were 11 months in patients with EGFR wild-type tumors versus 8.3 months in patients with EGFR-mutant tumors, 11.6 months in smokers versus 10.0 months in never-smokers, 11.0 months in never-smokers with EGFR wild-type tumors versus 5.6 months in never-smokers with EGFR-mutant tumors, and 14.1 months in smokers with EGFR-mutant tumors versus 11.3 months in smokers with EGFR wild-type tumors. CONCLUSIONS: The data on the Italian expanded access program in populations with nonsquamous NSCLC suggest that subgroups of patients could benefit differently from nivolumab according to their EGFR mutational status and smoking habits. These results warrant further investigation.
Authors: Siwen Hu-Lieskovan; Aaron Lisberg; Jesse M Zaretsky; Tristan R Grogan; Hira Rizvi; Daniel K Wells; James Carroll; Amy Cummings; John Madrigal; Benjamin Jones; Jacklin Gukasyan; I Peter Shintaku; Dennis Slamon; Steven Dubinett; Jonathan W Goldman; David Elashoff; Matthew D Hellmann; Antoni Ribas; Edward B Garon Journal: Clin Cancer Res Date: 2019-05-21 Impact factor: 12.531
Authors: Mitchell S von Itzstein; Amrit S Gonugunta; Helen G Mayo; John D Minna; David E Gerber Journal: Cancer J Date: 2020 Nov/Dec Impact factor: 2.074