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Review

Novel precision therapies for cholangiocarcinoma: an overview of clinical trials

ORCID Icon, , &
Pages 69-75 | Received 30 Nov 2022, Accepted 23 Jan 2023, Published online: 30 Jan 2023

References

  • Sung H, Ferlay J, Siegel RL, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries.” CA. Cancer J Clinicians. 2021;71.3:209–249.
  • Saha SK, Zhu AX, Fuchs CS, et al. Forty-year trends in cholangiocarcinoma incidence in the US: intrahepatic disease on the rise. Oncologist. 2016;21.5:594–599.
  • Uson Junior PLS, Bogenberger J, Borad MJ. Advances in the treatment of biliary tract cancers. Curr Op Gastroenterol. 2020;36.2:85–89.
  • PLS UJ, Borad MJ. Precision approaches for cholangiocarcinoma: progress in clinical trials and beyond. Expert Opin Investig Drugs. 2022;31(1):125–131.
  • Oh D-Y, He AR, Qin S, et al. Durvalumab plus gemcitabine and cisplatin in advanced biliary tract cancer. NEJM Evidence; 2022. p. EVIDoa2200015. Doi:10.1056/EVIDoa2200015.
  • Berchuck JE, Facchinetti F, DiToro D, et al. The clinical landscape of cell-free DNA alterations in 1,671 patients with advanced biliary tract cancer. Ann Oncol. 2022;33.12:1269–1283.
  • Uson Junior PLS, Majeed U, Yin J, et al. Cell-free tumor DNA dominant clone allele frequency is associated with poor outcomes in advanced biliary cancers treated with platinum-based chemotherapy. JCO Precision Oncol. 2022;6.1:e2100274.
  • De Luca A, Abate RE, Rachiglio AM, et al. FGFR fusions in cancer: from diagnostic approaches to therapeutic intervention. Int J Mol Sci. 2020;21.18:6856.
  • Katoh M. Fibroblast growth factor receptors as treatment targets in clinical oncology. Nat Rev Clin Oncol. 2019;16.2:105–122.
  • Ahn DH, PLS UJ, Masci P, et al. A pilot study of Pan-FGFR inhibitor ponatinib in patients with FGFR-altered advanced cholangiocarcinoma. Investig New Drugs. 2022;40.1:134–141.
  • Abou-Alfa GK, Sahai V, Hollebecque A, et al. Pemigatinib for previously treated, locally advanced or metastatic cholangiocarcinoma: a multicentre, open-label, phase 2 study. Lancet Oncol. 2020;21(5):671–684.
  • Liu PC, Koblish H, Wu L, et al. INCB054828 (pemigatinib), a potent and selective inhibitor of fibroblast growth factor receptors 1, 2, and 3, displays activity against genetically defined tumor models. PLoS One. 2020;15(4):e0231877.
  • Subbiah V, Ianotti NO, Gutierrez M, et al. FIGHT-101, a first-in-human study of potent and selective FGFR 1-3 inhibitor pemigatinib in pan-cancer patients with FGF/FGFR alterations and advanced malignancies. Ann Oncol. 2022;33.5:522–533.
  • Bekaii-Saab TS, Valle JW, Van Cutsem E, et al. FIGHT-302: phase III study of first-line (1L) pemigatinib (PEM) versus gemcitabine (GEM) plus cisplatin (CIS) for cholangiocarcinoma (CCA) with FGFR2 fusions or rearrangements. J Clin Oncol. 2020;38(abstr): TPS592.
  • Javle M, Lowery M, Shroff RT, et al. Phase II study of BGJ398 in patients with FGFR-altered advanced cholangiocarcinoma. J clin oncol. 2018;36.3:276.
  • Javle M, Roychowdhury S, Kelley RK, et al. Final results from a phase II study of infigratinib (BGJ398), an FGFR-selective tyrosine kinase inhibitor, in patients with previously treated advanced cholangiocarcinoma harboring an FGFR2 gene fusion or rearrangement. J Clin Oncol. 2021;39(abstr):265.
  • Makawita S, Abou-Alfa K, Roychowdhury, S G, et al. Infigratinib in patients with advanced cholangiocarcinoma with FGFR2 gene fusions/translocations: the PROOF 301 trial. Fut Oncol. 2020;16(30):2375–2384.
  • Bahleda R, Meric-Bernstam F, Goyal L, et al. Phase I, first-in-human study of futibatinib, a highly selective, irreversible FGFR1–4 inhibitor in patients with advanced solid tumors. Ann Oncol. 2020;31.10:1405–1412.
  • Goyal L, Meric-Bernstam F, Hollebecque A, et al. Updated results of the FOENIX-CCA2 trial: efficacy and safety of futibatinib in intrahepatic cholangiocarcinoma (iCCA) harboring FGFR2 fusions/rearrangements. In J Clin Oncol. 2022. Vol. 40: 4009. Doi:10.1200/JCO.2022.40.16.
  • Borad MJ, Bridgewater JA, Morizane C, et al. A phase III study of futibatinib (Tas-120) versus gemcitabine-cisplatin (gem-cis) chemotherapy as first-line (1L) treatment for patients (pts) with advanced (adv) cholangiocarcinoma (CCA) harboring fibroblast growth factor receptor 2 (FGFR2) gene rearrangements (FOENIX-CCA3). J Clin Oncol. 2020;38(abstr): TPS600.
  • Mazzaferro V, El-Rayes BF, Busset MDD, et al. Derazantinib (ARQ 087) in advanced or inoperable FGFR2 gene fusion-positive intrahepatic cholangiocarcinoma. Br J Cancer. 2019;120.2:165–171.
  • Busset MDD, Shaib WL, Harris WP, et al. 45P efficacy of derazantinib in intrahepatic cholangiocarcinoma patients with FGFR2 mutations or amplifications: pooled analysis of clinical trials and early access programs. Ann Oncol. 2020;31:S1231.
  • Borad MJ, Javle M, Shaib WL, et al. 59P efficacy of derazantinib in intrahepatic cholangiocarcinoma (iCCA) patients with FGFR2 fusions, mutations or amplifications. Ann Oncol. 2022;33:S567–S568.
  • Park JO, Feng Y-H, Chen -Y-Y, et al. Updated results of a phase IIa study to evaluate the clinical efficacy and safety of erdafitinib in Asian advanced cholangiocarcinoma (CCA) patients with FGFR alterations. In J Clin Oncol. 2019. Vol. 37: 4117. Doi:10.1200/JCO.2019.37.15.
  • Loriot Y, Schuler MH, Iyer G, et al. Tumor agnostic efficacy and safety of erdafitinib in patients (pts) with advanced solid tumors with prespecified fibroblast growth factor receptor alterations (FGFRalt) in RAGNAR: interim analysis (IA) results. J Clin Oncol. 2022;40(abstr):3007.
  • Cleary JM, Iyer G, D-Y O, et al. Final results from the phase I study expansion cohort of the selective FGFRi Debio 1,347 in patients with solid tumors harboring an FGFR gene fusion. J Clin Oncol. 2020;38(abstr):3603.
  • Hollebecque A, Borad M, Goyal L, et al. LBA12 Efficacy of RLY-4008, a highly selective FGFR2 inhibitor in patients (pts) with an FGFR2-fusion or rearrangement (f/r), FGFR inhibitor (FGFRi)-naïve cholangiocarcinoma (CCA): reFocus trial. Ann Oncol. 2022;33(abstr):S1381.
  • Lowery MA, Burris 3rd HA, Janku F, et al. Safety and activity of ivosidenib in patients with IDH1-mutant advanced cholangiocarcinoma: a phase 1 study. Lancet Gastroenterol Hepatol. 2019;4(9):711–720.
  • Zhu AX, Macarulla T, Javle MM, et al. Final results from ClarIDHy, a global, phase III, randomized, double-blind study of ivosidenib (IVO) versus placebo (PBO) in patients (pts) with previously treated cholangiocarcinoma (CCA) and an isocitrate dehydrogenase 1 (IDH1) mutation. In J Clin Oncol. 2021. Vol. 39: 266. Doi:10.1200/JCO.2021.39.3.
  • Abou-Alfa GK, Macarulla T, Javle MM, et al. Ivosidenib in IDH1-mutant, chemotherapy-refractory cholangiocarcinoma (ClarIDHy): a multicentre, randomised, double-blind, placebo-controlled, phase 3 study. Lancet Oncol. 2020;21.6:796–807.
  • Ramanathan RK, Belani CP, Singh DA, et al. A phase II study of lapatinib in patients with advanced biliary tree and hepatocellular cancer. Cancer Chemother Pharmacol. 2009;64.4:777–783.
  • Peck J, Wei L, Zalupski M, et al. HER2/neu may not be an interesting target in biliary cancers: results of an early phase II study with lapatinib. Oncology. 2012;82.3:175–179.
  • Javle MM, D-Y O, Ikeda M, et al. Varlitinib plus capecitabine in second-line advanced biliary tract cancer: a randomized, phase II study (TreeTopp). ESMO open. 2022;7.1:100314.
  • Harding J, Cleary J, Shapiro G, et al. Treating HER2-mutant advanced biliary tract cancer with neratinib: benefits of HER2-directed targeted therapy in the phase 2 SUMMIT ‘basket’trial. Ann Oncol. 2019;30:iv127.
  • MM J, MJ B, NS A, et al. Pertuzumab and trastuzumab for HER2-positive, metastatic biliary tract cancer (MyPathway): a multicentre, open-label, phase 2a, multiple basket study. Lancet Oncol. 2021;22.9:1290–1300.
  • Meric-Bernstam F, Beeram M, Hamilton E, et al. Zanidatamab, a novel bispecific antibody, for the treatment of locally advanced or metastatic HER2-expressing or HER2-amplified cancers: a phase 1, dose-escalation and expansion study. Lancet Oncol. 2022;23.12:1558–1570.
  • Ohba A, Morizane C, Kawamoto Y, et al. Trastuzumab deruxtecan (T-DXd; DS-8201) in patients (pts) with HER2-expressing unresectable or recurrent biliary tract cancer (BTC): an investigator-initiated multicenter phase 2 study (HERB trial). J Clin Oncol. 2022;40(abstr):4006.
  • Lee C-K, Chon HJ, Cheon J, et al. Trastuzumab plus FOLFOX for HER2-positive biliary tract cancer refractory to gemcitabine and cisplatin: a multi-institutional phase 2 trial of the Korean cancer study group (KCSG-HB19–14). Lancet Gastroenterol Hepatol. 2023;8.1:56–65.
  • Subbiah V, Lassen U, Élez E, et al. Dabrafenib plus trametinib in patients with BRAFV600E-mutated biliary tract cancer (ROAR): a phase 2, open-label, single-arm, multicentre basket trial. Lancet Oncol. 2020;21.9:1234–1243.
  • Meric-Bernstam F, Rothe M, Garrett-Mayer E, et al. Cobimetinib plus vemurafenib (C+ V) in patients (Pts) with solid tumors with BRAF V600E/d/k/R mutation: results from the targeted agent and profiling utilization registry (TAPUR) study. J Clin Oncol. 2022;40(abstr):3008.
  • Lamarca A, Palmer DH, Wasan HS, et al. Second-line FOLFOX chemotherapy versus active symptom control for advanced biliary tract cancer (ABC-06): a phase 3, open-label, randomised, controlled trial. Lancet Oncol. 2021;22.5:690–701.
  • Goyal L, Saha SK, Liu LY, et al. Polyclonal secondary FGFR2 mutations drive acquired resistance to FGFR inhibition in patients with FGFR2 fusion–positive cholangiocarcinoma. Cancer Disc. 2017;7(3):252–263.
  • Silverman IM, Hollebecque A, Friboulet L, et al. Clinicogenomic analysis of FGFR2-rearranged cholangiocarcinoma identifies correlates of response and mechanisms of resistance to pemigatinib. Cancer Disc. 2021;11.2:326–339.
  • Lau DK, Jenkins L, Weickhardt A. Mechanisms of acquired resistance to fibroblast growth factor receptor targeted therapy. Cancer Drug Resist. 2019;2:568–579.
  • Mayr C, Kiesslich T, Modest DP, et al. Chemoresistance and resistance to targeted therapies in biliary tract cancer: what have we learned? Expert Opin Investig Drugs. 2022;31.2:221–233.
  • Marin JJG, Macias RIR. Understanding drug resistance mechanisms in cholangiocarcinoma: assisting the clinical development of investigational drugs. Expert Opin Investig Drugs. 2021;30.7:675–679.
  • Cleary JM, Rouaisnel B, Daina A, et al. Secondary IDH1 resistance mutations and oncogenic IDH2 mutations cause acquired resistance to ivosidenib in cholangiocarcinoma. NPJ Prec Oncol. 2022;6.1:1–8.
  • Reinbold R, Hvinden IC, Rabe P, et al. Resistance to the isocitrate dehydrogenase 1 mutant inhibitor ivosidenib can be overcome by alternative dimer-interface binding inhibitors. Nat Comm. 2022;13.1:1–12.
  • Uson Junior PLS, DeLeon TT, Bogenberger JM, et al. FGFR2-IIIb expression by immunohistochemistry has high specificity in cholangiocarcinoma with FGFR2 genomic alterations. Dig Dis Sci. 2022;67(8):3797–3805.
  • Garralda E, Hong D, Xu R, et al. SO-31 Long-term efficacy and safety of larotrectinib in patients with tropomyosin receptor kinase (TRK) fusion gastrointestinal (GI) cancer: an expanded dataset. In Ann Oncol. 2022. Vol. 33: S370. Doi:10.1016/j.annonc.2022.04.430.
  • Solomon JP, Linkov I, Rosado A, et al. NTRK fusion detection across multiple assays and 33,997 cases: diagnostic implications and pitfalls. Mod Pathol. 2020;33(1):38–46.
  • Marabelle A, Le DT, PA A, et al. Efficacy of pembrolizumab in patients with noncolorectal high microsatellite instability/mismatch repair–deficient cancer: results from the phase II KEYNOTE-158 study. J Clin Oncol. 2020;38(1):1–10.

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