Metastatic Colorectal Cancer: Regorafenib
Kanwal Raghav, MBBS, MD, explains the rationale for using regorafenib for metastatic colorectal cancer and reviews data from 2 clinical trials.
Kanwal Raghav, MBBS, MD: I agree with the use of regorafenib in this setting because the data so far have demonstrated an overall survival benefit. If you think about these patients who have received almost 2 years of chemotherapy, they invariably develop adverse effects that are specific to chemotherapy, especially bone marrow toxicity, such as low platelets, anemia, and sometimes even leucopenia. This bone marrow toxicity is a tough issue to continue further chemotherapy in which case a nonchemotherapy option or a more anti-VEGF option, such as regorafenib, becomes an obvious choice because you won’t be able to challenge patients with a chemotherapy option for a long period of time in these cases.
Regorafenib is a very reasonable third-line option, of course with the schema that clinical trials should definitely be options for all our patients—across the lines, because there is always a limited efficacy of all our options, even though our first- and second-line options are better than third-line options. Clinical trial is always my third option if available. If not, then regorafenib is the reasonable third-line option along with TAS-102 [tipiracil hydrochloride].
The data that tell us this comes from a couple of randomized controlled trials. The largest of these was the CORRECT trial, which randomized 700 patients across this regorafenib vs placebo. It clearly showed an overall survival benefit of about 6.4 months compared with 5 months in the placebo arm. Even though the response rates are not high, this is definitely a disease-control rate benefit from 15% to about 40% with regorafenib.
This kind of performance has been repeated in other randomized trials, such as the CONCUR study, which is predominantly the Asian population. There was also the IMblaze370 study, which compared the combination of cobimetinib and atezolizumab and used regorafenib as a control arm. The response as well as the toxicities were very similar to our experience in CORRECT and CONCUR.
Furthermore, there was another randomized phase 2 study called the ReDOS study. The study compared 2 dosing strategies of regorafenib. In 1 of them, it was a standard dose of 160 mg; in the other, it was a dose-escalation strategy. This was a great study to show that even a dose-escalation strategy can result in good outcomes. Overall survival was numerically better, even though it’s not powered for that. The comparison was numerically better. It was about 9½ months vs 6 months from a dose escalation vs a standard dose treatment. But the primary end point with that study was how many patients started a third cycle. It was actually higher in the dose-escalation strategy than a standard-dose strategy, about 40% vs 25%. Regorafenib with a ReDOS approach, which is starting with 80 mg and then uptitrating all the way to 160 mg as tolerated, has been our go-to strategy for third-line options.
Transcript edited for clarity.
Case Overview: A 72-Year-Old Woman With Metastatic Colorectal Cancer
May 2018
Initial presentation
A 72-year-old woman reported a 2-month history of bloating and abdominal cramping, and an 8-pound unintentional weight loss
Her last screening colonoscopy when she was 70 years of age was negative
PMH: hysterectomy at age 60, high blood pressure well controlled with lisinopril
Clinical workup
Labs: Hg 8.4 g/dL, CEA 6 ng/mL
Colonoscopy revealed a 9-cm mass in ascending colon
Pathology: invasive, poorly differentiated adenocarcinoma
Molecular testing: KRAS, NRAS, and BRAF wildtype; microsatellite stable
CT scan revealed widespread lesions in the liver
Diagnosis: Stage 4 colorectal cancer
ECOG PS is 1
Treatment
The patient received systemic therapy with FOLFOX + bevacizumab for 6 cycles, which was well tolerated
Follow-up imaging at 2 months and 4 months showed response in liver lesions
The patient continued on bevacizumab maintenance
June 2019
- The patient presents with shortness of breath and fatigue
- CT CAP shows two new lung lesions and growth of liver lesions
- The patient is switched to FOLFIRI and cetuximab
- Follow-up imaging showed stable disease in liver and lungs
August 2020
- The patient reports severe fatigue
- CT CAP shows progression in the lungs and new bony lesions
- The patient is given regorafenib alone
Further Evaluation of Regorafenib/Nivolumab Is Recommended in Rectal Cancer
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