By Steven J. Cohen, MD
MK is a 58-year-old male plumber with metastatic colon cancer who presents for a discussion of treatment options.
Relevant Medical History
Clinical Presentation/Laboratory Tests
- Diagnosed in 2014 when he experienced abdominal pain.
- Computed tomography (CT) scan revealed multiple liver and peritoneal masses.
- Colonoscopy revealed descending colon mass – biopsy was adenocarcinoma.
- Expanded RAS testing was negative for mutation (wild-type).
- He received FOLFIRI/cetuximab with initial response then progressive disease.
- He subsequently received FOLFOX/bevacizumab with response but experienced subsequent progressive disease last month.
- He currently has abdominal pain and some fatigue.
- His Eastern Cooperative Oncology Group performance status is 1.
- His complete blood count and comprehensive metabolic panel results are essentially unremarkable.
Given progressive expanded RAS-wild type metastatic colon cancer after FOLFIRI/cetuximab and FOLFOX/bevacizumab, MK’s oncologist is considering additional systemic therapy.
See Question 1
The patient is actually begun on regorafenib 160 mg orally once daily on days 1 to 21 of each 4-week cycle. After 2 months on therapy, repeat imaging reveals stable disease. However, MK develops grade 3 hypertension that requires the prescription of antihypertensive therapy.
See Question 2
Submit your diagnosis to see full explanation.
Question 1 Explanation
Patients with RAS-wild-type metastatic colon cancer who have been previously treated with oxaliplatin- and irinotecan-based chemotherapy, an anti-vascular endothelial growth factor (VEGF) biological therapy, and an anti-epidermal growth factor receptor (EGFR) therapy (if expanded RAS wild-type) can next receive oral systemic therapy with either trifluridine + tipiracil or regorafenib, according to the National Comprehensive Cancer Network colon cancer guidelines.1
Trifluridine + tipiracil hydrochloride (TAS-102) has demonstrated efficacy in this treatment setting in a phase 3 study comparing TAS-102 with placebo. The study demonstrated a significant improvement in overall and progression-free survival with TAS-102 compared to placebo.2,3
Capecitabine + oxaliplatin, panitumumab, irinotecan + ramucirumab, or FOLFOXIRI + bevacizumab would not be appropriate choices because the patient’s disease has already progressed on 5-FU, irinotecan, oxaliplatin, bevacizumab, and an anti-EGFR antibody.1
Question 2 Explanation
Regorafenib treatment should be interrupted for any National Cancer Institute Common Terminology Criteria for Adverse Events grade 3 or 4 adverse reaction. It is recommended that BP be checked weekly for the first 6 weeks of therapy and then every cycle or as clinically indicated.
After the recovery of any grade 3 or 4 adverse reaction, the dose of regorafenib may be reduced to 120 mg daily. The dose may be further reduced to 80 mg daily following treatment interruption if another grade 3 or 4 adverse reaction occurs at the 120 mg dose (except hepatotoxicity).4
- National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines): Colon Cancer. V 2.2016. http://www.nccn.org/professionals/physician_gls/pdf/colon.pdf. Accessed April 4, 2016.
- Lonsurf (trifluridine and tipiracil) [prescribing information]. Princeton, NJ: Taiho Oncology, Inc. http://www.accessdata.fda.gov/drugsatfda_docs/label/2015/207981s000lbl.pdf. Accessed February 10, 2016.
- Mayer RJ, van Cutsem E, Falcone A, et al. Randomized trial of TAS-102 for refractory metastatic colorectal cancer. N Engl J Med. 2015;372(20):1909-1919.
- Stivarga (regorafenib) [prescribing information]. Whippany, NJ: Bayer HealthCare Pharmaceuticals Inc. http://labeling.bayerhealthcare.com/html/products/pi/Stivarga_PI.pdf. Accessed April 6, 2016.