Genomic Analysis of Exceptional Responder to Regorafenib in Treatment-refractory Metastatic Rectal Cancer: a Case Report and Review of the Literature

Overview

Journal Oncotarget

Specialty Oncology

Date 2017 Sep 17

PMID 28915719

Citations 6

Authors

Krittiya Korphaisarn

Jonathan M Loree

Van Nguyen

Ryanne Coulson

Vijaykumar Holla

Beate C Litzenburger

Ken Chen

Gordon B Mills

Dipen M Maru

Funda Meric-Bernstan

Kenna R Mills Shaw

Scott Kopetz

Affiliations

Soon will be listed here.

Abstract

We present the case of a 53-year-old male with metastatic rectal cancer who was treatment resistant to FOLFOX and FOLFOXIRI. Due to a Kirsten rat sarcoma viral oncogene homolog () mutation, regorafenib was given in the third line setting. Surprisingly, the patient had a prolonged partial response that lasted 27 months. Mutational status was extensively evaluated to identify potential alterations that might play a role as predictive markers for this unusual event. A poorly characterized but nontransforming mutation in Fms-like tyrosine kinase 4 () was present in the tumor. Prior to and at the time of clinical progression, we found amplification of fibroblast growth factor receptor 1 ( epidermal growth factor receptor , loss of the mutation, and gain of proto-oncogene receptor tyrosine kinase G961S suggesting potential roles in acquired resistance.

Citing Articles

Case report: Unique FLT4 variants associated with differential response to anlotinib in angiosarcoma.

Gu Y, Meng J, Ju Y, You X, Sun T, Lu J Front Oncol. 2022; 12:1027696.

PMID: 36452496 PMC: 9702819. DOI: 10.3389/fonc.2022.1027696.

Clinical and molecular distinctions in patients with refractory colon cancer who benefit from regorafenib treatment.

Lee M, Cho H, Hong J, Lee J, Park S, Park J Ther Adv Med Oncol. 2020; 12:1758835920965842.

PMID: 33224274 PMC: 7649869. DOI: 10.1177/1758835920965842.

VEGF-C is positively associated with lymphangiogenesis and lymphatic metastasis in rectal cancer.

Pan Z, Lu X, Zhao J, Gao Q, Wang J Int J Clin Exp Pathol. 2020; 11(3):1777-1783.

PMID: 31938284 PMC: 6958173.

Long-term survival of an advanced colorectal cancer patient treated with Regorafenib: Case report and literature review.

Brunetti O, Calabrese A, Palermo L, Solimando A, Argentiero A Clin Case Rep. 2020; 7(12):2379-2383.

PMID: 31893063 PMC: 6935656. DOI: 10.1002/ccr3.2496.

Signet ring cell colorectal cancer: genomic insights into a rare subpopulation of colorectal adenocarcinoma.

Korphaisarn K, Morris V, Davis J, Overman M, Fogelman D, Kee B Br J Cancer. 2019; 121(6):505-510.

PMID: 31406299 PMC: 6738104. DOI: 10.1038/s41416-019-0548-9.

References

Strumberg D, Schultheis B . Regorafenib for cancer. Expert Opin Investig Drugs. 2012; 21(6):879-89. DOI: 10.1517/13543784.2012.684752. View

Grothey A, Van Cutsem E, Sobrero A, Siena S, Falcone A, Ychou M . Regorafenib monotherapy for previously treated metastatic colorectal cancer (CORRECT): an international, multicentre, randomised, placebo-controlled, phase 3 trial. Lancet. 2012; 381(9863):303-12. DOI: 10.1016/S0140-6736(12)61900-X. View

Leto S, Trusolino L . Primary and acquired resistance to EGFR-targeted therapies in colorectal cancer: impact on future treatment strategies. J Mol Med (Berl). 2014; 92(7):709-22. PMC: 4055851. DOI: 10.1007/s00109-014-1161-2. View

Summy J, Gallick G . Treatment for advanced tumors: SRC reclaims center stage. Clin Cancer Res. 2006; 12(5):1398-401. DOI: 10.1158/1078-0432.CCR-05-2692. View

Freier K, Schwaenen C, Sticht C, Flechtenmacher C, Muhling J, Hofele C . Recurrent FGFR1 amplification and high FGFR1 protein expression in oral squamous cell carcinoma (OSCC). Oral Oncol. 2006; 43(1):60-6. DOI: 10.1016/j.oraloncology.2006.01.005. View

Abajo A, Bitarte N, Zarate R, Boni V, Lopez I, Gonzalez-Huarriz M . Identification of colorectal cancer metastasis markers by an angiogenesis-related cytokine-antibody array. World J Gastroenterol. 2012; 18(7):637-45. PMC: 3281220. DOI: 10.3748/wjg.v18.i7.637. View

Dogruluk T, Tsang Y, Espitia M, Chen F, Chen T, Chong Z . Identification of Variant-Specific Functions of PIK3CA by Rapid Phenotyping of Rare Mutations. Cancer Res. 2015; 75(24):5341-54. PMC: 4681596. DOI: 10.1158/0008-5472.CAN-15-1654. View

Eisen T, Joensuu H, Nathan P, Harper P, Wojtukiewicz M, Nicholson S . Regorafenib for patients with previously untreated metastatic or unresectable renal-cell carcinoma: a single-group phase 2 trial. Lancet Oncol. 2012; 13(10):1055-62. DOI: 10.1016/S1470-2045(12)70364-9. View

Li J, Qin S, Xu R, Yau T, Ma B, Pan H . Regorafenib plus best supportive care versus placebo plus best supportive care in Asian patients with previously treated metastatic colorectal cancer (CONCUR): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2015; 16(6):619-29. DOI: 10.1016/S1470-2045(15)70156-7. View

10.

Tabernero J, Lenz H, Siena S, Sobrero A, Falcone A, Ychou M . Analysis of circulating DNA and protein biomarkers to predict the clinical activity of regorafenib and assess prognosis in patients with metastatic colorectal cancer: a retrospective, exploratory analysis of the CORRECT trial. Lancet Oncol. 2015; 16(8):937-48. PMC: 7513622. DOI: 10.1016/S1470-2045(15)00138-2. View

11.

Mross K, Frost A, Steinbild S, Hedbom S, Buchert M, Fasol U . A phase I dose-escalation study of regorafenib (BAY 73-4506), an inhibitor of oncogenic, angiogenic, and stromal kinases, in patients with advanced solid tumors. Clin Cancer Res. 2012; 18(9):2658-67. DOI: 10.1158/1078-0432.CCR-11-1900. View

12.

Yonesaka K, Zejnullahu K, Okamoto I, Satoh T, Cappuzzo F, Souglakos J . Activation of ERBB2 signaling causes resistance to the EGFR-directed therapeutic antibody cetuximab. Sci Transl Med. 2011; 3(99):99ra86. PMC: 3268675. DOI: 10.1126/scitranslmed.3002442. View

13.

Galland F, Karamysheva A, Pebusque M, Borg J, Rottapel R, Dubreuil P . The FLT4 gene encodes a transmembrane tyrosine kinase related to the vascular endothelial growth factor receptor. Oncogene. 1993; 8(5):1233-40. View

14.

Bandla S, Pennathur A, Luketich J, Beer D, Lin L, Bass A . Comparative genomics of esophageal adenocarcinoma and squamous cell carcinoma. Ann Thorac Surg. 2012; 93(4):1101-6. PMC: 3401935. DOI: 10.1016/j.athoracsur.2012.01.064. View

15.

Pawson T . Regulation and targets of receptor tyrosine kinases. Eur J Cancer. 2003; 38 Suppl 5:S3-10. DOI: 10.1016/s0959-8049(02)80597-4. View

16.

Jiang T, Gao G, Fan G, Li M, Zhou C . FGFR1 amplification in lung squamous cell carcinoma: a systematic review with meta-analysis. Lung Cancer. 2014; 87(1):1-7. DOI: 10.1016/j.lungcan.2014.11.009. View

17.

Gao J, Aksoy B, Dogrusoz U, Dresdner G, Gross B, Sumer S . Integrative analysis of complex cancer genomics and clinical profiles using the cBioPortal. Sci Signal. 2013; 6(269):pl1. PMC: 4160307. DOI: 10.1126/scisignal.2004088. View

18.

Mirone G, Perna S, Shukla A, Marfe G . Involvement of Notch-1 in Resistance to Regorafenib in Colon Cancer Cells. J Cell Physiol. 2015; 231(5):1097-105. DOI: 10.1002/jcp.25206. View

19.

Eisenhauer E, Therasse P, Bogaerts J, Schwartz L, Sargent D, Ford R . New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer. 2008; 45(2):228-47. DOI: 10.1016/j.ejca.2008.10.026. View

20.

Corcoran R, Dias-Santagata D, Bergethon K, Iafrate A, Settleman J, Engelman J . BRAF gene amplification can promote acquired resistance to MEK inhibitors in cancer cells harboring the BRAF V600E mutation. Sci Signal. 2010; 3(149):ra84. PMC: 3372405. DOI: 10.1126/scisignal.2001148. View