Sara Pilotto1, Antonio Rossi2, Tiziana Vavalà3, Alessandro Follador4, Marcello Tiseo5, Domenico Galetta6, Alessandro Morabito7, Massimo Di Maio8, Olga Martelli9, Orazio Caffo10, Pier Luigi Piovano11, Diego Cortinovis12, Nicoletta Zilembo13, Clelia Casartelli14, Giuseppe Luigi Banna15, Antonio Ardizzoia16, Maria Luisa Barzelloni2, Alessandra Bearz17, Giovenzio Genestreti18, Claudia Mucciarini19, Virginio Filipazzi20, Jessica Menis4, Elisa Rizzo21, Fausto Barbieri22, Erika Rijavec23, Fabiana Cecere24, Gianluca Spitaleri25, Emilio Bria26, Silvia Novello3. 1. Medical Oncology, University of Verona, Azienda Ospedaliera Universitaria Integrata di Verona, Verona, Italy. Electronic address: sara.pilotto@univr.it. 2. Division of Medical Oncology, S.G. Moscati Hospital, Avellino, Italy. 3. Department of Oncology, University of Torino AOU San Luigi, Torino, Italy. 4. Department of Oncology, University Hospital of Udine, Udine, Italy. 5. Medical Oncology Unit, University Hospital of Parma, Parma, Italy. 6. Medical Oncology Unit, Clinical Cancer Center Giovanni Paolo II, Bari, Italy. 7. Thoracic Medical Oncology, National Cancer Institute, Fondazione "G. Pascale", Napoli, Italy. 8. Medical Oncology, Mauriziano Hospital, Department of Oncology, University of Turin, Torino, Italy. 9. Medical Oncology, S. Giovanni-Addolorata Hospital, Roma, Italy. 10. Medical Oncology Unit, Santa Chiara Hospital, Trento, Italy. 11. Medical Oncology Unit, AO SS. Antonio Biagio e Cesare Arrigo, Alessandria, Italy. 12. Medical Oncology Unit, AOU San Gerardo, Monza, Italy. 13. Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy. 14. Medical Oncology Unit, Valduce Hospital, Como, Italy. 15. Division of Medical Oncology, AO Cannizzaro Hospital, Catania, Italy. 16. Medical Oncology Unit, A. Manzoni Hospital, Lecco, Italy. 17. Department of Medical Oncology, National Institute for Cancer Research, Aviano, Italy. 18. Department of Medical Oncology, IRCCS Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST), Meldola, Italy. 19. Department of Oncological Medicine, Ramazzini Hospital, Carpi, Italy. 20. UOC Medical Oncology, AO Luigi Sacco, Milano, Italy. 21. EORTC Headquarters, Bruxelles, Belgium. 22. Department of Oncology and Hemathology, AOU of Modena, Modena, Italy. 23. Lung Cancer Unit, IRCCS AOU San Martino-IST Istituto Nazionale per la Ricerca sul Cancro, Genova, Italy. 24. Medical Oncology Unit, University Hospital Careggi, Firenze, Italy. 25. Division of Thoracic Oncology, European Institute of Oncology, Milano, Italy. 26. Medical Oncology, University of Verona, Azienda Ospedaliera Universitaria Integrata di Verona, Verona, Italy.
Abstract
BACKGROUND: Beyond progression after tyrosine kinase inhibitor in EGFR-positive non-small-cell lung cancer patients (BE-POSITIVE) was the first Italian multicenter observational study that reported the outcomes of first-generation epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) in a "real-life" Caucasian EGFR-mutated non-small-cell lung cancer (NSCLC) population. The sharing of multi-institutional experiences represents a crucial strategy to enrich knowledge about uncommon EGFR mutations. Therefore, we performed a post hoc analysis of the BE-POSITIVE study. PATIENTS AND METHODS: Data of advanced NSCLC patients with uncommon EGFR mutations who received first-line first-generation EGFR-TKIs in 24 Italian Hospitals were collected. In this analysis we aimed to evaluate overall survival (OS), progression-free survival (PFS), and overall response rate (ORR) of EGFR-TKIs in NSCLC patients harboring uncommon EGFR mutations. RESULTS: Thirty-five patients harboring uncommon EGFR mutations (any mutation other than deletion 19 or substitution of leucine by arginine at codon 858) were included of the original 312 EGFR-mutated cases. Most of them were female (n = 20, 57.1%), former smokers (n = 23, 65.7%), with adenocarcinoma (n = 31, 88.6%). The most frequent EGFR mutations were G719X (n = 6, 17.2%) and L861Q (n = 5, 14.2%). The population presented an ORR of 25.7%, a median PFS of 5.19 months, and a median OS of 14.49 months. When stratified according to type of EGFR mutation, median OS ranged from 3.65 months for unspecified mutations to 21.29 for double EGFR mutations. Median PFS ranged from 1.77 months for unspecified mutations to 20.83 months for concomitant EGFR-anaplastic lymphoma kinase alteration. ORR varied from 0% in exon 18, 20 and double gene alteration to 66.6% in exon 19. CONCLUSION: Our study supports the existence of a strong outcome heterogeneity within patients harboring uncommon EGFR mutations, which needs to be clarified to achieve a real personalized treatment strategy.
BACKGROUND: Beyond progression after tyrosine kinase inhibitor in EGFR-positive non-small-cell lung cancerpatients (BE-POSITIVE) was the first Italian multicenter observational study that reported the outcomes of first-generation epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) in a "real-life" Caucasian EGFR-mutated non-small-cell lung cancer (NSCLC) population. The sharing of multi-institutional experiences represents a crucial strategy to enrich knowledge about uncommon EGFR mutations. Therefore, we performed a post hoc analysis of the BE-POSITIVE study. PATIENTS AND METHODS: Data of advanced NSCLCpatients with uncommon EGFR mutations who received first-line first-generation EGFR-TKIs in 24 Italian Hospitals were collected. In this analysis we aimed to evaluate overall survival (OS), progression-free survival (PFS), and overall response rate (ORR) of EGFR-TKIs in NSCLCpatients harboring uncommon EGFR mutations. RESULTS: Thirty-five patients harboring uncommon EGFR mutations (any mutation other than deletion 19 or substitution of leucine by arginine at codon 858) were included of the original 312 EGFR-mutated cases. Most of them were female (n = 20, 57.1%), former smokers (n = 23, 65.7%), with adenocarcinoma (n = 31, 88.6%). The most frequent EGFR mutations were G719X (n = 6, 17.2%) and L861Q (n = 5, 14.2%). The population presented an ORR of 25.7%, a median PFS of 5.19 months, and a median OS of 14.49 months. When stratified according to type of EGFR mutation, median OS ranged from 3.65 months for unspecified mutations to 21.29 for double EGFR mutations. Median PFS ranged from 1.77 months for unspecified mutations to 20.83 months for concomitant EGFR-anaplastic lymphoma kinase alteration. ORR varied from 0% in exon 18, 20 and double gene alteration to 66.6% in exon 19. CONCLUSION: Our study supports the existence of a strong outcome heterogeneity within patients harboring uncommon EGFR mutations, which needs to be clarified to achieve a real personalized treatment strategy.
Authors: Xiuyu Cai; Zhenghe Chen; Meiling Deng; Zhiyong Li; Qianchao Wu; Jinwang Wei; Chun Dai; Guan Wang; Chun Luo Journal: Ann Transl Med Date: 2020-09
Authors: Giuseppe Luigi Banna; Timothée Olivier; Francesco Rundo; Umberto Malapelle; Filippo Fraggetta; Massimo Libra; Alfredo Addeo Journal: Front Med (Lausanne) Date: 2019-07-31