e-Poster Presentation Clinical Oncology Society of Australia Annual Scientific Meeting 2020

Systemic treatment with a RET inhibitor (LOXO-292) in a patient with metastatic colorectal cancer with RET fusion (NCOA4-RET). (#216)

Sabeeh-ur-Rehman SB Butt 1 2 , Marlene MH Happe 3 , Gonzalo GT Torga 2 , Anna AP Patrikidou 2 4 , Hendrik-Tobias HTA Arkenau 2 4
  1. Alan Walker Cancer Centre, Tiwi, NT, Australia
  2. Sarah Cannon Research Institute, London, United Kingdom
  3. School of Medicine, University of Cologne, Cologne, Germany
  4. University College London, London, United Kingdom

Targeted therapies in colorectal cancer (CRC) are currently mostly limited to the unresectable or metastatic setting [1,2,3,4,5,6]. The incorporation of molecular profiling technologies to the clinic in synergy with the broadening of targeted agents and druggable genomic aberration landscape has increased traction lately towards incorporating molecularly targeted therapies as single-agents or in combination to well-established chemotherapy schemes [7]. Alterations involving “rearranged during transfection” (RET) kinases are such potential targets. RET is a proto-oncogene whose loss of function mutations are associated with the development of Hirschsprung's disease and gain of function mutations are associated with the development of various types of human cancer, however, they are rare in CRC [8]. We present a case of a patient with CRC with RET fusion treated with a LOXO-292, a selective RET-inhibitor leading to an exceptional response, highlighting the impact of next-generation genome sequencing on the clinical management of CRC patients and reinforcing the notion that RET alterations are actionable therapeutic targets when present despite the tumor type. Although the incidence of RET fusions in CRC is low, prospective use of next-generation genome profiling should be encouraged to identify patients who may potentially benefit from selective RET inhibition.


  1. 1. Hurwitz H, Fehrenbacher L, Novotny W, et al. Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer. N Engl J Med. 2004;350(23):2335-2342
  2. 2. Cunningham D, Humblet Y, Siena S, et al. Cetuximab monotherapy and cetuximab plus irinotecan in irinotecan-refractory metastatic colorectal cancer. N Engl J Med. 2004;351(4):337-345
  3. 3. Van Cutsem E, Peeters M, Siena S, et al. Open-label phase III trial of panitumumab plus best supportive care compared with best supportive care alone in patients with chemotherapy- refractory metastatic colorectal cancer. J Clin Oncol. 2007;25(13):1658-1664
  4. 4. Tabernero J, Yoshino T, Cohn AL. Ramucirumab versus placebo in combination with second-line FOLFIRI in patients with metastatic colorectal carcinoma that progressed during or after first-line therapy with bevacizumab, oxaliplatin, and a fluoropyrimidine (RAISE): a randomised, double-blind, multicentre, phase 3 study. [Correction to Lancet Oncol. 2015;16:499-508]. Lancet Oncol. 2015;16(6):e262.
  5. 5. Van Cutsem E, Joulain F, Hoff PM, et al. Aflibercept plus FOLFIRI vs. placebo plus FOLFIRI in second-line metastatic colorectal cancer: a post hoc analysis of survival from the phase III VELOUR study subsequent to exclusion of patients who had recurrence during or within 6 months of completing adjuvant oxaliplatin-based therapy. Target Oncol. 2016;11(3):383- 400
  6. 6. Grothey A, Van Cutsem E, Sobrero A, et al; CORRECT Study Group. Regorafenib monotherapy for previously treated metastatic colorectal cancer (CORRECT): an international, multicentre, randomised, placebo-controlled, phase 3 trial. Lancet. 2013;381(9863):303- 312.
  7. 7. Kopetz S, Grothey A, Yaeger R, et al. Encorafenib, Binimetinib, and Cetuximab in BRAF V600E–Mutated Colorectal Cancer. N Engl J Med 2019; 381:1632-1643
  8. 8. Stransky N, Cerami E, Schalm S, Kim JL, and Lengauer C. The landscape of kinase fusions in cancer. Nat Commun. 2014;5:4846