Options for Wild-Type Patients in CRC

Case 1: A 70-year old female with type 2 diabetes mellitus and a 1.5 cm tumor in the sigmoid colon.

Options for Wild-Type Patients in CRC

Michael Morse, MD:This is a 70-year-old woman with type 2 diabetes. She’s otherwise in good health and has a very good performance status, PS0. She has liver and lung metastasis. Molecular testing shows that this was RAS wild-type, including KRAS and NRAS, also BRAF wild-type and microsatellite stable. She initiated therapy with FOLFIRI plus cetuximab. This is very reasonable as there are several options for first-line therapy, including chemotherapy such as FOLFOX or FOLFIRI and then a biologic, either an antiangiogenic agent such as bevacizumab or an anti-EGFR agent such as cetuximab or panitumumab in a RAS wild-type patient.

This was a very reasonable choice for first-line therapy as there are several options. First we choose the chemotherapy. There’s FOLFOX or FOLFIRI, although some patients even receive a single agent. Generally, we choose the chemotherapy based on patients’ comorbidities, or their hobbies, or interests. Some patients may not want the toxicity of oxaliplatin, for example, with the neuropathy. Other patients may be concerned about hair loss or excessive diarrhea that may occur with irinotecan. Then we choose the biologic; bevacizumab as an antiangiogenic drug or one of the EGFR-targeted therapies such as cetuximab or panitumumab. Again, this is partially patient choice as the EGFR-targeted therapies cause a rash which can persist throughout the therapy, although it definitely improves over time.

Assuming this patient has already had the standard chemotherapies such as a fluoropyrimidine, and oxaliplatin, and irinotecan and has also had the biologic agents such as bevacizumab and since they’re RAS wild-type, and EGFR-targeted therapy such as cetuximab or panitumumab, there are two main options for therapy — trifluridine plus tipiracil which was previously called TAS-102 and regorafenib.

Case Scenario 1:

• This is a 70-year old woman who 3 years ago presented with bloody stool.
• Medical history included type 2 diabetes; no other comorbidities.
• A colonoscopy revealed a 1.5 cm tumor in the sigmoid colon.
• A CT scan revealed multiple hepatic and pulmonary lesions.
• Biopsy of liver lesion and colon mass showed moderately differentiated adenocarcinoma, KRAS, NRAS, BRAF wild-type and MSS.
• Her ECOG performance status at the time was 0.
• FOLFIRI plus cetuximab was initiated.
• She later developed progressive disease.
• She was given FOLFOX plus bevacizumab.
• Her ECOG performance status is now 1.