Frontline Therapy for Stage IV Right-Sided CRC

Bassel F. El-Rayes, MD:The current recommendation from the NCCN [National Comprehensive Cancer Network] for patients with stage IV colon cancer who are wild-type forRAFandRASis to start out with combination chemotherapy, if they are in good performance status, plus bevacizumab. Combination chemotherapy is usually a fluoropyrimidine, like 5-FU [fluorouracil] or capecitabine, in combination with either oxaliplatin or irinotecan. There are a number of trials that have shown that the combination of the fluoropyrimidine plus oxaliplatin is equivalent to a fluoropyrimidine plus irinotecan, so those options of chemotherapy could be used interchangeably in this setting.

In my practice, I tend to use FOLFOX [folinic acid, fluorouracil, and oxaliplatin] plus bevacizumab as a first-line choice in stage IV colon cancer patients, especially if they have right-sided tumors or have mutations in theRASpathway. The reason for choice of bevacizumab is based on the sidedness and the mutational panel. The reason for oxaliplatin rather than irinotecan is a preference related to the side effect profile of the drugs. But that being said, using bevacizumab and FOLFIRI [folinic acid, fluorouracil, and irinotecan] in the frontline setting is a very acceptable standard of care as well.

So for younger patients who are very well fit, there is an option for using a triplet regimen, which includes 5-FU, oxaliplatin, and irinotecan up front in combination with bevacizumab. An approach like that would carry a higher chance of response, but it does carry a higher chance, also, for side effects. And, therefore, you have to be very judicious in who you select for the triplet regimen versus the doublet regimen. On the other end of the spectrum, for older patients, like patients in their 80s and above, or patients who have borderline performance status, there is also option of using a single chemotherapy regimen with bevacizumab, and the regimen that’s most commonly used is capecitabine plus bevacizumab in that setting.

If this patient had left-sided colon cancer, the options for therapy in the frontline setting would be more complex. Patients with left-sided colon cancer who areRASwild-type could either start with a combination chemotherapy plus bevacizumab, or combination chemotherapy plus an EGFR inhibitor. Both options would be viable options in that population. Physician’s choice between bevacizumab versus an EGFR inhibitor depends on differences in side effects and patient preference. But efficacy-wise, the 2 regimens appear to be acceptable options in left-sided colon cancer.

My personal preference in practice is to use bevacizumab up front because I feel that the side effects of the bevacizumab are less intrusive as compared to the side effects of EGFR inhibitors. And specifically, I’m talking about issues related to skin toxicities, which can be very intrusive in a patient’s quality of life.

Transcript edited for clarity.

Case: A 75-Year-Old ManWithRight-Sided mCRC

Initial presentation

• A 75-year-old Caucasian man presented to his PCP with rectal bleeding, fatigue, weight loss, and constipation

Clinical workup

• Colonoscopy: fungating mass in the ascending colon
• Biopsy: invasive, poorly differentiated adenocarcinoma
• Imaging: CT scan of the chest/abdomen/pelvis showed multiple small liver lesions including a 3-cm mass in right lobe
• Molecular testing on tissue biopsy:
  • KRAS, RAS, andBRAFWT
  • Microsatellite-stable
• ECOG PS 1

Treatment

• Patient underwent a diverting colostomy without complication
• He was started on FOLFOX and bevacizumab
• Follow up imaging at 3, 6, and 9 months showed a partial response
• He was continued on bevacizumab and underwent capecitabine maintenance
• Imaging at 12 months showed 2 new liver lesions (1.2 cm and 3.4 cm)