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Two case studies of patients with advanced CRC who experience disease progression on multiple lines of therapy are discussed by Cathy Eng, MD. Both case studies involve the use of regorafenib as a third-line agent.
Case Study 1
The first clinical scenario involves a patient who is a 57-year-old male, with stage IV CRC, ECOG performance status 0-1, and KRAS
Presuming the patient has a nonresectable tumor; Eng would start by confirming KRAS
status and testing for other rare RAS
mutations. If the results show all-RAS
wild-type, Eng would discuss therapy options, including the potential benefit from EGFR therapy upfront, as shown in the FIRE-3 study, as well as more classic regimens such as FOFOX or FOLFIRI. If the patient is worried about side effects, Eng would probably use FOLFIRI/bevacizumab. Eng would take into account the patient’s lifestyle and preference when deciding whether to use FOLFOX or FOLFIRI.
Should this patient experience disease progression, Eng would treat with FOLFOX/bevacizumab. Aflibercept would not be an option in this setting because it is approved for use with FOLFIRI. If this patient experiences disease progression after second-line therapy, Eng would use an anti-EGFR therapy combination. If the patient again experiences progression, Eng would consider regorafenib.
Case Study 2
The second clinical scenario discussed involves a patient who is a 72-year-old female with stage IV CRC, ECOG performance status 1-2, and KRAS
In an elderly patient who has borderline performance status, Eng would start off with capecitabine- or 5-FU–based regimen including bevacizumab, as long as the patient has no contraindications to bevacizumab. In the APEX trial, which looked at patients older than 70 years, capecitabine was used. However, creatinine clearance has to be carefully monitored with capecitabine.
If the patient experiences disease progression, Eng would still consider anti-VEGF therapy in the second-line setting if appropriate. If an elderly patient tolerates therapy with capecitabine or 5-FU, Eng would consider adding oxaliplatin or irinotecan.
As third-line therapy for this patient, Eng would consider regorafenib, assuming the patient’s liver function is within normal limits and her performance status is good. Caution should be exercised when giving chemotherapy to a frail patient.