Goals of Therapy in Third-Line CRC

Marwan G. Fakih, MD:This is a 70-year-old female with a past medical history significant for diabetes. The patient developed rectal bleeding approximately 3 years ago. This led to further workup, including a colonoscopy. The colonoscopy showed a sigmoid tumor, and this was biopsied showing adenocarcinoma. The patient had further workup, including CT scans of the chest, abdomen, and pelvis. The CT scans showed multiple metastatic lesions in the lung and in the liver. A biopsy of one of the metastatic lesions in the liver showed an adenocarcinoma consistent with colorectal cancer. Molecular profiling confirmed that this tumor was RAS wild-type, BRAF wild-type.

The patient received FOLFIRI and cetuximab for her first-line treatment. She had an initial response followed by disease progression. The patient has an ECOG performance status of 1 now. She received FOLFOX and bevacizumab as second-line therapy. The patient developed progressive disease.

Now that the patient has progressed on first- and second-line chemotherapy, we have to consider a third-line option. The options of treatment for a patient who has progressed on irinotecan, oxaliplatin, and a fluoropyrimidine, as well as anti-EGFR therapy in the setting of a RAS wild-type tumor, is either regorafenib as monotherapy or TAS-102, which is trifluridine and tipiracil.

Our goal, at this point, is to continue to improve the overall survival of our patient. But, also important goals in the management of patients with metastatic colorectal cancer are to improve their functionality, to diminish the chances of worsening in performance status, and decrease their symptomatology.

This is an appropriate patient for TAS-102 monotherapy. The reason for such is that the patient has a good performance status, she has progressed on first- and second-line treatment, and she has no further option of cytotoxic chemotherapy. This would be an ideal candidate for TAS-102.

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.