EGFR Blockade as Effective Therapy in BRAF and EGFR Mutated Metastatic Colorectal Cancer: Learning from a Clinical Case

Special Article – Surgery Case Reports

Austin J Surg. 2019; 6(4): 1167.

EGFR Blockade as Effective Therapy in BRAF and EGFR Mutated Metastatic Colorectal Cancer: Learning from a Clinical Case

Ghiglione L¹, Esposito F¹, Pagés M², Jares P³ and Maurel J¹*

¹Department of Medical Oncology, IDIBAPS, Universitat de Barcelona c/ Villarroel, Spain

²Department of Radiology, Centre de Diagnòstic per la Imatge Clínic (CDIC), Spain

³Department of Anatomic Pathology, Hospital Clinic of Barcelona, University of Barcelona, Barcelona, Spain

*Corresponding author: Joan Maurel, Medical Oncology Department, Hospital Clínic, Translational Genomics and Targeted Therapeutics in Solid Tumors Group, IDIBAPS, Universitat de Barcelona, c/ Villarroel, Spain

Received: December 31, 2018; Accepted: February 08, 2019; Published: February 15, 2019


Metastatic colorectal cancer patients affected of BRAF mutations are associated with poor prognosis. The co-association with EGFR mutation in the tyrosine kinase domain is quite low. We report a case of an EGFR and BRAF mutated patient and its unexpected outcome. A search through the literature for EGFR mutated and information about its response to EGFR blockade was perform. Likewise, we reviewed our own cohort of patients. The case presented and our analysis reinforces the importance of using next generation sequencing to discover unusual mutations tributary of anti-EGFR therapy.

Keywords: EGFR mutated; BRAF mutated; Metastatic colorectal cancer; NGS; Cetuximab


Colorectal Cancer (CRC) is the second most commonly diagnosed cancer and one of the leading causes of cancer deaths worldwide. Approximately 50% of metastatic CRC harbour RAS mutations and predicts anti-EGFR compounds (cetuximab and panitumumab) resistance [1]. Roughly, 5% of mCRC have microsatellite instability (MSI) and these patients are sensitive to immune checkpoint blockade [2]. BRAF mutation is associated with poor prognosis [3] but the role is still controversial as a predictive marker of anti-EGFR therapy [4- 6]. Next generation sequencing (NGS) allows to evaluate targeteddriven genes that are rarely mutated, fussed or amplified in mCRC (HER2, EGFR, MET and FGFR) and there use in clinical setting is currently increasing.

We present a case of a BRAF mutant patient mCRC, who experienced a long-term complete response with FOLFOX plus cetuximab in the POSIBA trial (NCT01276379).

Case Presentation

A 44-year-old Caucasian woman was referred due to abdominal pain and anaemia on April 2012. Blood test revealed Hb 11 gr/dL and CEA 9.5 ng/mL (reference range <5 ng/mL). An abdominal Computed Tomography (CT) scan described a mass on the left side colon and pathologic retroperitoneal lymph nodes. Colonoscopy reports a left colonic lesion. While preparation for surgical intervention, she presented symptoms of intestinal obstruction and a subtotal colectomy was done on April 27, 2012. Pathologic specimen shows a high-grade mucinous adenocarcinoma, pT3N2 (33/66), KRAS (exon 2) Wild Type (WT). Postoperative thoracoabdominal CT described pathologic mesenteric, retroperitoneal and mediastinal lymph nodes. PET-CT showed lymph nodes with increased metabolic activity in the same territory depicted on the CT. Because of the unusual presentation with thoracic lymph nodes, a bronchoscopy with biopsy was performed reporting adenocarcinoma (CAM5.2+). Patient was included in the clinical trial POSIBA on July 2012 and received FOLFOX6m plus cetuximab 500 mg/m2 every 2 weeks for 12 cycles followed by cetuximab monotherapy discontinued because of grade 3 cutaneous toxicity in 17th cycle on March 2013. A 3-month reevaluation CT showed a complete response which is maintained until today on June 2018 (Figure 1). Extended RAS and BRAF mutations were done per protocol on 10/2015 and a BRAF (V600E) mutation was detected.