Andrea Necchi1, Salvatore Lo Vullo2, Daniele Raggi3, Annunziata Gloghini4, Patrizia Giannatempo3, Maurizio Colecchia4, Luigi Mariani2. 1. Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy. Electronic address: andrea.necchi@istitutotumori.mi.it. 2. Clinical Epidemiology and Trials Organization Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy. 3. Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy. 4. Department of Pathology and Laboratory Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
Abstract
FGFR gene alterations represent a target for treatment in clinical trials of urothelial carcinoma (UC). Little is known about their prognostic effect in patients with metastatic UC. We analyzed data for 112 patients treated with platinum-based first-line chemotherapy at our center between October 2011 and March 2017 and who were screened for the presence of FGFR mutations or gene fusions within multiple clinical trials with pan-FGFR inhibitors. Centralized targeted exome sequencing analyses were performed to detect multiple FGFR mutations and fusions. Cox regression analyses were performed, adjusting for recognized prognostic factors. Thirty-seven patients (33%) had upper tract UC (UTUC). A total of 22 patients (19.6%) had FGFR alterations and ten (8.9%) received salvage pan-FGFR inhibitor therapy. Thirty-two patients (45.4%) received salvage treatment with an immune checkpoint inhibitor. FGFR alterations were more frequently observed in UTUC versus bladder UC (p=0.017). On multivariable analyses, FGFR alterations were not significantly associated with OS (p=0.860) or PFS (p=0.147) after first-line chemotherapy. PATIENT SUMMARY: In an original single-center study, FGFR gene alterations were not prognostic for either progression-free survival or overall survival in patients receiving first-line chemotherapy for metastatic urothelial carcinoma. These results will be useful in interpreting findings from future clinical trials.
FGFR gene alterations represent a target for treatment in clinical trials of urothelial carcinoma (UC). Little is known about their prognostic effect in patients with metastatic UC. We analyzed data for 112 patients treated with platinum-based first-line chemotherapy at our center between October 2011 and March 2017 and who were screened for the presence of FGFR mutations or gene fusions within multiple clinical trials with pan-FGFR inhibitors. Centralized targeted exome sequencing analyses were performed to detect multiple FGFR mutations and fusions. Cox regression analyses were performed, adjusting for recognized prognostic factors. Thirty-seven patients (33%) had upper tract UC (UTUC). A total of 22 patients (19.6%) had FGFR alterations and ten (8.9%) received salvage pan-FGFR inhibitor therapy. Thirty-two patients (45.4%) received salvage treatment with an immune checkpoint inhibitor. FGFR alterations were more frequently observed in UTUC versus bladder UC (p=0.017). On multivariable analyses, FGFR alterations were not significantly associated with OS (p=0.860) or PFS (p=0.147) after first-line chemotherapy. PATIENT SUMMARY: In an original single-center study, FGFR gene alterations were not prognostic for either progression-free survival or overall survival in patients receiving first-line chemotherapy for metastatic urothelial carcinoma. These results will be useful in interpreting findings from future clinical trials.
Authors: Constance Le Goux; Sophie Vacher; Anne Schnitzler; Nicolas Barry Delongchamps; Marc Zerbib; Michael Peyromaure; Mathilde Sibony; Yves Allory; Ivan Bieche; Diane Damotte; Geraldine Pignot Journal: Sci Rep Date: 2020-10-06 Impact factor: 4.379