Hepatology research : the official journal of the Japan Society of Hepatology · 2025
FGFR2 Fusions or Rearrangements in Young Intrahepatic and Perihilar Cholangiocarcinoma Patients: Key Genetic Insights From a Pan-Asian Study.
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Maruki Yuta, Yatabe Yasushi, Mizoguchi Chiharu, de Almeida Kathleen Yasmin, Sookprasert Aumkhae, Akewanlop Charuwan, Chen Ming-Huang, Sirachainan Ekaphop, Tu Dao Van, Malik Rozita Abdul, Charoentum Chaiyut, Hoo Hwoei Fen Soo, Yusak Suhana, Liu Tsung-Hao, Ramachandran Rangasamy, Sunpaweravong Patrapim, Voon Pei Jye, Bakar Najihah Abu, Mizusawa Junki, Okuma Hitomi Sumiyoshi, Nakamura Kenichi, Morizane Chigusa, Okusaka Takuji
Аннотация
AIM: Biliary tract cancers, including intrahepatic cholangiocarcinoma (ICC), are aggressive with limited treatment options and poor prognosis. Recent trials (TOPAZ-1, Keynote-966) showed improved survival with ICIs plus gemcitabine and cisplatin. Targeted therapies, including FGFR inhibitors, are promising for cholangiocarcinoma patients with FGFR2 gene fusions or rearrangements, although few reports exist on FGFR2 positivity and clinical data in Asia. This study aims to address this gap by evaluating FGFR2 fusions or rearrangements in intrahepatic and perihilar cholangiocarcinoma patients across Asia, providing insights into their clinical significance and potential therapeutic implications.
METHODS: This multicenter study evaluated the frequency of FGFR2 rearrangements and fusion genes in ICC and perihilar cholangiocarcinoma across Asia (Thailand, Malaysia, Vietnam, and Taiwan) using fluorescence in situ hybridization (FISH) and comprehensive genomic profiling with the Todai OncoPanel2 (TOP2).
RESULTS: Of 113 patients, 102 were eligible; FGFR2 rearrangements/fusions were found in 3.9% (4 cases) by FISH, all of which were also confirmed by the TOP2 panel, consistent with the Japanese PRELUDE study. Younger age was significantly associated with FGFR2 positivity (34.5 ± 3.17 vs. 62.69 ± 1.04; p = 0.0003), whereas no correlation was observed with hepatitis infection, alcohol use, or smoking history. Genomic profiling identified frequent mutations in TP53, KRAS, and ARID1A with notable regional variability. Patients treated with ICIs showed significantly longer progression-free survival compared to other therapies: ICI + cytotoxic (348 days, 95% CI: 0-897), platinum-based + GEM (240 days, 95% CI: 197-282), and other treatments (168 days, 95% CI: 11-325; p = 0.017).
CONCLUSION: The FGFR2 positivity rate in Asia is slightly lower but consistent with Japanese reports and is more common in younger patients with ICC. Distinct genetic alterations may characterize Asian populations.
METHODS: This multicenter study evaluated the frequency of FGFR2 rearrangements and fusion genes in ICC and perihilar cholangiocarcinoma across Asia (Thailand, Malaysia, Vietnam, and Taiwan) using fluorescence in situ hybridization (FISH) and comprehensive genomic profiling with the Todai OncoPanel2 (TOP2).
RESULTS: Of 113 patients, 102 were eligible; FGFR2 rearrangements/fusions were found in 3.9% (4 cases) by FISH, all of which were also confirmed by the TOP2 panel, consistent with the Japanese PRELUDE study. Younger age was significantly associated with FGFR2 positivity (34.5 ± 3.17 vs. 62.69 ± 1.04; p = 0.0003), whereas no correlation was observed with hepatitis infection, alcohol use, or smoking history. Genomic profiling identified frequent mutations in TP53, KRAS, and ARID1A with notable regional variability. Patients treated with ICIs showed significantly longer progression-free survival compared to other therapies: ICI + cytotoxic (348 days, 95% CI: 0-897), platinum-based + GEM (240 days, 95% CI: 197-282), and other treatments (168 days, 95% CI: 11-325; p = 0.017).
CONCLUSION: The FGFR2 positivity rate in Asia is slightly lower but consistent with Japanese reports and is more common in younger patients with ICC. Distinct genetic alterations may characterize Asian populations.