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Drug Evaluation

Entrectinib: a potent new TRK, ROS1, and ALK inhibitor

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Bibliography

  • Ciardiello F, Arnold D, Casali PG, et al. Delivering precision medicine in oncology today and in future-the promise and challenges of personalised cancer medicine: a position paper by the European Society for Medical Oncology (ESMO). Ann Oncol 2014;25(9):73–78.
  • Collins I, Workman P. New approaches to molecular cancer therapeutics. Nat Chem Biol 2006;2(12):689–700.
  • Chen VW, Ruiz BA, Hsieh MC, et al. Analysis of stage and clinical/prognostic factors for lung cancer from SEER registries: AJCC staging and collaborative stage data collection system. Cancer 2014;120(Suppl 23):3781–92.
  • Schiller JH, Harrington D, Belani CP, et al. Eastern Cooperative Oncology Group. Comparison of four chemotherapy regimens for advanced non-small-cell lung cancer. N Engl J Med 2002;346(2):92–8.
  • Mok T, Wu YL, Thongprasert S, et al. Gefitinib or carboplatin-paclitaxel in pulmonary adenocarcinoma. N Engl J Med 2009;361:947–57.
  • Rosell R, Carcereny E, Gervais R, et al. Erlotinib versus standard chemotherapy as first-line treatment for European patients with advanced EGFR mutation-positive non-small-cell lung cancer (EURTAC): a multicentre open-label randomised phase 3 trial. Lancet Oncol 2012;13:239–46.
  • Sequist LV, Yang JC, Yamamoto N, et al. Phase III study of afatinib orcisplatin plus pemetrexed in patients with metastatic lung adenocarcinoma with EGFR mutations. J Clin Oncol 2013;31:3327–34.
  • Shaw AT, Kim DW, Nakagawa K, et al. Crizotinib versus chemotherapy in advanced ALK-positive lung cancer. N Engl J Med 2013;368:2385–94.
  • Robinson DR, Wu YM, Lin SF. The protein tyrosine kinase family of the human genome. Oncogene 2000;19(49):5548–57.
  • Blume-Jensen P, Hunter T. Oncogenic kinase signalling. Nature 2001;411:355–65.

* Important review on oncogenic kinase signaling.

* Important review on tyrosine kinase signaling.

  • Zwick E, Bange J, Ullrich A. Receptor tyrosine kinases as targets for anticancer drugs. Trends Mol Med 2002;8(1):17–23.
  • Schlessinger J. Cell signaling by receptor tyrosine kinases. Cell 2000;103(2):211–25.
  • Narayanan R, Yepuru M, Coss CC, et al. Discovery and preclinical characterization of novel small molecule TRK and ROS1 tyrosine kinase inhibitors for the treatment of cancer and inflammation. PLoS ONE 2013;8(12):e83380.
  • Cameron L, Solomon B. Treatment of ALK-rearranged non-small cell lung cancer: recent progress and future directions. Drugs 2015;75(10):1059–70.

* Important and complete review on ALK-positive NSCLC.

  • Iwahara T, Fujimoto J, Wen D, et al. Molecular characterization of ALK, a receptor tyrosine kinase expressed specifically in the nervous system. Oncogene 1997;14(4):439–49.
  • Morris SW, Kirstein MN, Valentine MB, et al. Fusion of a kinase gene, ALK, to a nucleolar protein gene, NPM, in non-Hodgkin’s lymphoma. Science 1994;263(5151):81–1284.
  • Hallberg B, Palmer RH. Mechanistic insight into ALK receptor tyrosine kinase in human cancer biology. Nat Rev Cancer 2013;13(10):685–700.
  • Solomon B, Varella-garcia M, Camidge DR. ALK gene rearrangements: a new therapeutic target in a molecularly defined subset of non-small cell lung cancer. J Thorac Oncol 2009;4(12):1450–54.
  • Soda M, Choi YL, Enomoto M, et al. Identification of the transforming EML4-ALK fusion gene in non-small-cell lung cancer. Nature 2007;448:561–6.
  • Acquaviva J, Wong R, Charest A. The multifaceted roles of the receptor tyrosine kinase ROS in development and cáncer. Biochim Biophys Acta 2009;1795:37–52.
  • Gu TL, Deng X, Huang F, et al. Survey of tyrosine kinase signaling reveals ROS kinase fusions in human cholangiocarcinoma. PLoS One 2011;6:e15640.
  • Davies KD, Doebele RC. Molecular pathways: ROS1 fusion proteins in cancer. Clin Cancer Res 2013;19(15):4040–5.
  • Bergethon K, Shaw AT, Ou SH, et al. ROS1 rearrangements define a unique molecular class of lung cancers. JCO 2012;30(8):863–70.
  • Ou SH, Tan J, Yen Y, et al. ROS1 as a ‘druggable’ receptor tyrosine kinase: lessons learned from inhibiting the ALK pathway. Expert Rev Anticancer Ther 2012;12(4):447–56.
  • Brodeur GM, Minturn JE, Ho R, et al. Trk receptor expression and inhibition in neuroblastomas. Clin Cancer Res 2009;15(10):3244–50.
  • Barbacid M. Structural and functional properties of the TRK family of neurotrophin receptors. Ann N Y Acad Sci 1995;766:442–58.
  • Nakagawara A. Trk receptor tyrosine kinases: a bridge between cancer and neural development. Cancer Lett 2001;169(2):107–14.

* Important review on Trk RTK role in normal development and cancer.

** Study that identified NTRK1 rearrangements by NGS or FISH in 3.3% of lung adenocarcinomas without known oncogenic alterations.

  • Lagadec C, Meignan S, Adriaenssens E, et al. TrkA overexpression enhances growth and metastasis of breast cancer cells. Oncogene 2009;28:1960–70.
  • Greco A, Miranda C, Pierotti MA. Rearrangements of NTRK1 gene in papillary thyroid carcinoma. Mol Cell Endocrinol 2010;321(1):44–9.
  • Martin-Zanca D, Hughes SH, Barbacid M. A human oncogene formed by the fusion of truncated tropomyosin and protein tyrosine kinase sequences. Nature 1986;319(6056):743–8.
  • Ardini E, Bosottia R, Lombardi A, et al. The TPM3-NTRK1 rearrangement is a recurring event in colorectal carcinoma and is associated with tumor sensitivity to TRKA kinase inhibition. Mol Oncol 2014;8(8):1495–507.
  • Harada T, Yatabe Y, Takeshita M, et al. Role and relevance of TrkB mutations and expression in NSCLC. Clin Cancer Res. 2011;17(9):2638–45.
  • Nakagawara A, Azar C, Scavarda N, et al. Expression and function of TRK-B and BDNF in human neuroblastomas. Mol Cell Biol 1994;14:759–67.
  • Sclabas GM, Fujioka S, Schmidt C, et al. Overexpression of tropomysin-related kinase B in metastatic human pancreatic cancer cells. Clin Cancer Res 2005;11:440–9.
  • Gainor JF, Shaw AT. Emerging paradigms in the development of resistance to tyrosine kinase inhibitors in lung cancer. J Clin Oncol 2013;31(31):3987–96.
  • Ardini E, Menichincheri M, De Ponti C, et al. Characterization of NMS‐E628, a small molecule inhibitor of anaplastic lymphoma kinase with antitumor efficacy in ALK‐dependent lymphoma and non‐small cell lung cancer models. Mol Cancer Ther 2009;8:12 suppl; abstr A243.

** Pre-clinical study showing entrectinib antitumor efficacy and its ability to cross the brain-blood barrier.

  • De Braud FG, Pilla L, Niger M, et al. Phase 1 open label, dose escalation study of RXDX101, an oral pantrk, ROS1, and ALK inhibitor, in patients with advanced solid tumors with relevant molecular alterations. J Clin Oncol 2014;32(5s) suppl; abstr 2502.

** First results of a Phase 1 dose escalation study of entrectinib in patients with advanced solid tumors with molecular alterations of TrKA, ROS 1 or ALK.

  • De Braud FG, Niger M, Damian S, et al. Alka-372-001: first-in-human, phase I study of entrectinib – an oral pan-trk, ROS1, and ALK inhibitor – in patients with advanced solid tumors with relevant molecular alterations. J Clin Oncol 2015;33(suppl; abstr 2517).

** Phase 1 study of entrectinib in patients with advanced solid tumors with molecular alterations of TrKA, ROS 1 or ALK.

  • Patel MR, Bauer TM, Liu SV, et al. STARTRK-1: phase 1/2a study of entrectinib, an oral Pan-Trk, ROS1, and ALK inhibitor, in patients with advanced solid tumors with relevant molecular alterations. J Clin Oncol 2015;33(suppl; abstr 2596).

** Phase 1 study of entrectinib in patients with advanced solid tumors with molecular alterations of TrK, ROS 1 or ALK.

  • Ardini E, Menichincheri M, Banfi P, et al. In vitro and in vivo activity of NMSE628 against ALK mutations resistant to Xalkori. Mol Cancer Ther 2011;10:11 Suppl; abstr A232.

** Pre-clinical study demonstrating entrictinib activity against ALK mutants responsible for crizotinib resistance.

  • Ardini E, Menichincheri M, Banfi P, et al. The ALK inhibitor NMS-E628 also potentially inhibits ROS1 and induces tumor regression in ROS-driven models [abstract]. In: Annual meeting of the American association for cancer research; Apr 6–10; Washington, DC. Philadelphia (PA): American Association for Cancer Research (AACR). Cancer Res. 2013;73(8 Suppl; abstract nr 2092).

** Pre-clinical study showing entrectinib antitumor efficacy regression in ROS-driven models.

  • Anderson D, Ciome M, Banfi P, et al. Inhibition of Trk-driven tumors by the pan-Trk inhibitor RXDX-101. EJC 2014;50(Supplement 6):101.
  • Ardini E, Lombardi A, De Ponti C, et al. Identification and preclinical characterization of NMS-P626, a potent, selective and orally bioavailable TrkA inhibitor with anti-tumor activity in a TrkA-dependent colorectal cancer. Poster presented at the 22nd AACR-NCI-EORTC symposium on molecular targets and cancer therapeutics; 2010 Nov 16e19 (Abstract); Berlin (Germany).
  • Iyer R, Wehrmann L, Golden R, et al. The TRK Inhibitor Entrectinib Enhances the Efficacy of Temozolomide and Irinotecan in a Xenograft Model of Neuroblastoma. Philadelphia (PA): American Association for Cancer Research (AACR), 2015. Abstract nr. 5390.

** In vitro study showing antitumoral activity of entrectinib either alone or in combination with chemotherapy, in a xenograft model of neuroblastoma.

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