Antonio Passaro1, Arsela Prelaj2, Laura Bonanno3, Marcello Tiseo4, Alessandro Tuzi5, Claudia Proto2, Rita Chiari6, Danilo Rocco7, Carlo Genova8, Claudio Sini9, Diego Cortinovis10, Sara Pilotto11, Lorenza Landi12, Chiara Bennati12, Andrea Camerini13, Luca Toschi14, Carlo Putzu15, Giulio Cerea16, Gianluca Spitaleri17, Federico Cappuzzo12, Filippo de Marinis17. 1. Division of Thoracic Oncology, IEO, European Institute of Oncology IRCCS, Milan, Italy. Electronic address: antonio.passaro@ieo.it. 2. Division of Thoracic Oncology, IRCCS, Istituto Nazionale Tumori, Milan, Italy. 3. Medical Oncology 2, Istituto Oncologico Veneto IRCCS, Padova, Italy. 4. Medical Oncology Unit, University Hospital of Parma, Parma, Italy. 5. Medical Oncology, ASST-Settelaghi, Varese, Varese, Italy. 6. Medical Oncology, Santa Maria della Misericordia Hospital, AOU di Perugia, Perugia, Italy. 7. Department of Oncology, AORN Vincenzo Monaldi, Naples, Italy. 8. Lung Cancer Unit, IRCCS AOU San Martino-IST, Genova, Italy. 9. Medical Oncology, Olbia Hospital, Olbia, Italy. 10. Medical Oncology Unit, San Gerardo Hospital, Monza, Italy. 11. Medical Oncology, University of Verona, AOUI Verona, Verona, Italy. 12. Onco-Hematology Department, AUSL Romagna, Ravenna, Italy. 13. Medical Oncology, Versilia Hospital and Istituto Toscano Tumori, Lido di Camaiore, Italy. 14. Medical Oncology, Humanitas Research Hospital, Rozzano, Italy. 15. Oncology Unit, Department of Clinical and Experimental Medicine, University of Sassari, Sassari, Italy. 16. Department of Oncology and Hemato-Oncology, Niguarda Cancer Center, Milan, Italy. 17. Division of Thoracic Oncology, IEO, European Institute of Oncology IRCCS, Milan, Italy.
Abstract
BACKGROUND: Molecular characterization of non-small-cell lung cancer (NSCLC), defined predictive and druggable mutations that greatly modified patient prognoses. The most frequent driver mutations detected in NSCLC are epidermal growth factor receptor (EGFR) mutations, accounting for approximately 90% of exon 19 deletions and exon 21 point mutations. The other EGFR mutations are classified as uncommon or nonclassical and include exon 18 point mutations, exon 20 insertions, and combined mutations, which present different sensitivity to tyrosine kinase inhibitor (TKI) targeting. PATIENTS AND METHODS: We collected data from EGFR TKI-naive patients with metastatic NSCLC, harboring EGFR exon 18 mutations and EGFR combined mutations treated with first- or second-generation EGFR TKIs. Efficacy end points were evaluated considering the activity of EGFR TKIs in exon 18 versus double-mutation EGFR groups. RESULTS: Eighty-eight patients harboring uncommon EGFR mutations were evaluated in our analysis, and subdivided into 2 group: complex mutations (cohort A = 46 patients) and double mutations in exon 18 (cohort B = 42 patients). The results showed a median progression-free survival of 8.3 versus 12.3 months (hazard ratio [HR], 0.65; P = .06) and a median overall survival of 17.0 versus 31.0 months (HR, 0.62, P = .04) favoring the EGFR combination group. Within the combination group, no detrimental effect was associated with exon 20 mutations. CONCLUSION: Our study confirmed that EGFR exon 18 and combination mutations might be considered potentially sensitive uncommon mutations, with a similar survival compared with the well known common EGFR mutations. Comparative analysis showed that patients with complex mutations achieved longer survival compared with the exon 18 group, without correlation with the presence of exon 20 mutations.
BACKGROUND: Molecular characterization of non-small-cell lung cancer (NSCLC), defined predictive and druggable mutations that greatly modified patient prognoses. The most frequent driver mutations detected in NSCLC are epidermal growth factor receptor (EGFR) mutations, accounting for approximately 90% of exon 19 deletions and exon 21 point mutations. The other EGFR mutations are classified as uncommon or nonclassical and include exon 18 point mutations, exon 20 insertions, and combined mutations, which present different sensitivity to tyrosine kinase inhibitor (TKI) targeting. PATIENTS AND METHODS: We collected data from EGFR TKI-naive patients with metastatic NSCLC, harboring EGFR exon 18 mutations and EGFR combined mutations treated with first- or second-generation EGFR TKIs. Efficacy end points were evaluated considering the activity of EGFR TKIs in exon 18 versus double-mutation EGFR groups. RESULTS: Eighty-eight patients harboring uncommon EGFR mutations were evaluated in our analysis, and subdivided into 2 group: complex mutations (cohort A = 46 patients) and double mutations in exon 18 (cohort B = 42 patients). The results showed a median progression-free survival of 8.3 versus 12.3 months (hazard ratio [HR], 0.65; P = .06) and a median overall survival of 17.0 versus 31.0 months (HR, 0.62, P = .04) favoring the EGFR combination group. Within the combination group, no detrimental effect was associated with exon 20 mutations. CONCLUSION: Our study confirmed that EGFR exon 18 and combination mutations might be considered potentially sensitive uncommon mutations, with a similar survival compared with the well known common EGFR mutations. Comparative analysis showed that patients with complex mutations achieved longer survival compared with the exon 18 group, without correlation with the presence of exon 20 mutations.
Authors: Tejas Patil; Rao Mushtaq; Sydney Marsh; Christine Azelby; Miheer Pujara; Kurtis D Davies; Dara L Aisner; William T Purcell; Erin L Schenk; Jose M Pacheco; Paul A Bunn; D Ross Camidge; Robert C Doebele Journal: Clin Lung Cancer Date: 2019-11-21 Impact factor: 4.785
Authors: Francesca Simionato; Lorenzo Calvetti; Marco Cosci; Silvia Scarparo; Giuseppe Aprile Journal: Onco Targets Ther Date: 2020-11-23 Impact factor: 4.147