Joon Young Hur1, Joseph Chao2, Kyung Kim3, Seung Tae Kim4, Kyoung-Mee Kim5, Samuel J Klempner6, Jeeyun Lee7. 1. Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea; Division of Hematology and Oncology, Department of Internal Medicine, Hanyang University Guri Hospital, Guri, South Korea. Electronic address: md.joon@gmail.com. 2. Department of Medical Oncology and Therapeutics Research, City of Hope Comprehensive Cancer Center, Duarte, CA, USA. Electronic address: JChao@coh.org. 3. Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea. Electronic address: kkyung412@gmail.com. 4. Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea. Electronic address: shty1@skku.edu. 5. Department of Pathology and Translational Genomics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea. Electronic address: kkmkys@skku.edu. 6. Department of Medicine, Massachusetts General Hospital Cancer Center, Boston, MA, USA; Harvard Medical School, Boston, MA, USA. Electronic address: sklempner@partners.org. 7. Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea. Electronic address: jyunlee@skku.edu.
Abstract
BACKGROUND: Recurrent FGFR2 amplification is observed in gastroesophageal cancers but clinical implications are unknown. We investigated the association of FGFR2 amplification with cytotoxic chemotherapy outcome in gastroesophageal cancer (GC) patients. METHODS: Between 2016 and 2018, we identified 1045 metastatic GC patients who received palliative fluoropyrimidine/platinum-based chemotherapy and underwent tumor genomic profiling at a tertiary hospital in Korea and two US cancer centers. We retrospectively identified FGFR2-amplified cases and abstracted clinicopathologic features and treatment outcomes. Cox proportional hazard regression model was used to evaluate the variables that demonstrated effects on progression free and overall survival PFS and OS. Descriptive statistics were used to correlate level of FGFR2 copy number amplification CNA and clinicopathological parameters. RESULTS: The incidence of FGFR2-amplified GC was 4.0 %. A total of 42 FGFR2-amplified GC patients were included and divided into high and lower FGFR2 amplification values. Fifteen patients had an FGFR2 CNA greater than 30, and 27 had a CNA of 30 or less. There was no significant differences between age, sex, tumor localization, Lauren classification, or tumor staging. After a median follow-up duration of 11.4 months, patients with high FGFR2 amplification had significantly poorer median PFS (3.2 vs. 4.8 months, hazard ratio (HR) 2.08, 95 % CI, 1.03-4.22, P = 0.042) and significantly shorter median OS (10.1 vs. 26.3 months, HR 2.99, 95 % CI = 1.05-8.49, P = 0.040) than the low FGFR2 amplification group. CONCLUSION: Recurrent FGFR2 amplification was observed in roughly 4.0 % of GC patients. High FGFR2 amplification was significantly associated with poor progression free survival and overall survival in GC patients. Clinical studies of FGFR2-directed therapies are warranted and should consider stratification by FGFR2 CNA.
BACKGROUND: Recurrent FGFR2 amplification is observed in gastroesophageal cancers but clinical implications are unknown. We investigated the association of FGFR2 amplification with cytotoxic chemotherapy outcome in gastroesophageal cancer (GC) patients. METHODS: Between 2016 and 2018, we identified 1045 metastatic GCpatients who received palliative fluoropyrimidine/platinum-based chemotherapy and underwent tumor genomic profiling at a tertiary hospital in Korea and two US cancer centers. We retrospectively identified FGFR2-amplified cases and abstracted clinicopathologic features and treatment outcomes. Cox proportional hazard regression model was used to evaluate the variables that demonstrated effects on progression free and overall survival PFS and OS. Descriptive statistics were used to correlate level of FGFR2 copy number amplification CNA and clinicopathological parameters. RESULTS: The incidence of FGFR2-amplified GC was 4.0 %. A total of 42 FGFR2-amplified GCpatients were included and divided into high and lower FGFR2 amplification values. Fifteen patients had an FGFR2 CNA greater than 30, and 27 had a CNA of 30 or less. There was no significant differences between age, sex, tumor localization, Lauren classification, or tumor staging. After a median follow-up duration of 11.4 months, patients with high FGFR2 amplification had significantly poorer median PFS (3.2 vs. 4.8 months, hazard ratio (HR) 2.08, 95 % CI, 1.03-4.22, P = 0.042) and significantly shorter median OS (10.1 vs. 26.3 months, HR 2.99, 95 % CI = 1.05-8.49, P = 0.040) than the low FGFR2 amplification group. CONCLUSION: Recurrent FGFR2 amplification was observed in roughly 4.0 % of GCpatients. High FGFR2 amplification was significantly associated with poor progression free survival and overall survival in GCpatients. Clinical studies of FGFR2-directed therapies are warranted and should consider stratification by FGFR2 CNA.
Authors: Nicole M Myer; Kohei Shitara; Hyun C Chung; Florian Lordick; Ronan J Kelly; Zsolt Szabo; Z Alexander Cao; Stephen Leong; David H Ilson; Wilko Weichert Journal: J Cancer Res Clin Oncol Date: 2022-05-13 Impact factor: 4.322