Optimal Treatment of Chemoresistant mCRC - Episode 2

Treatment Overview of a Patient with Relapsed mCRC

March 13, 2019

Tanios Bekaii-Saab, MD, FACP:When the patient presented first with his early stage cancer, the patient was tested for microsatellite instability [MSI] which is pretty routine. The lymph node yield or harvest was adequate. We had a good idea about his projected prognosis. With IIIA, this is considered low-risk. Those patients survive at a rate of 80, 85%. It’s not 100%. That’s why we keep close observation. We know at least 15% to 20% of those patients ultimately will progress and will have disease recurrence. The choice of chemotherapy was primarily based on the results of the IDEA trial which asked the question of 3 month versus 6 month and the choice between Folfox and Capox, depending on the study that was included or physician choice.

From the IDEA trial, 2 things came about. One, that Capox is probably preferable over Folfox, and for low-risk such as stage IIIA, 3 months is not inferior to 6 months, especially with Capox. At that time, the decision was to essentially expose the patient to three month of chemotherapy and Capox specifically, based on those results, and then continue with close observation.

I think overall that the patient was treated adequately. He was staged adequately. He was low-risk, but, unfortunately, because of his right-sided tumor, I suspect his chances of recurrence were much higher than if it was on the left side. We know that, I mean we knew that even before all the right versus left discussions. In the metastatic setting started, we know from actually early in the 2000s or even a little bit the 1990s, that a lot of the adjuvant trials suggested that the right-sided tumors generally do worse than the left-sided tumors. And chemotherapy itself, at least in the earlier stages, does not seem to change the time course much of those right-sided tumors at the same level than the left-sided tumors.

The patient responded extremely well to Folfoxiri/bevacizumab, almost near complete resolution of the lesions. I mean, he still had few lesions left. They were not amenable to any locoregional therapy, and thus the decision was to continue with systemic chemotherapy. The question is what do you do after 3 months of Folfoxiri plus bevacizumab, 3 to 4 months of Folfoxiri plus bevacizumab. You can go straight to maintenance strategy with capecitabine plus bevacizumab or you can do what we call de-escalation. Since this patient had a significant neuropathy, the logical thing was to drop the oxaliplatin. And I think the reason why this patient had even worse neuropathy than I would expect for 3 month exposure is because he had prior exposure to oxaliplatin in the adjuvant setting. Usually 3 to 4 months should be fine without having major issues with neuropathy.

So the decision was to drop with Folfiri/bevacizumab. Although equally I think consider it would be to go to capecitabine plus bevacizumab maintenance. So he continued on Folfiri/bevacizumab for another 6 cycles which seemed to maintain a good response. And then after that you start having significant issues with toxicities such as this patient. Then it makes sense to go to what we typically do is capecitabine daily plus bevacizumab. In my clinic, I choose not to go daily, meaning nonstop, because especially in our US-based population, we have significant issues with hand and foot syndrome. A little break in between actually helps, and I find the 5 days continuous capecitabine and weekend breaks very helpful in terms of cutting down significantly on the risk of hand and foot syndrome. And that was the choice for this patient.

Transcript edited for clarity.

Case: A 60-Year-Old Male With mCRC

Initial presentation

April 2015

  • A 60-year—old man was referred to gastroenterology after complaining of general malaise and alternating constipation with bloody diarrhea.
  • PE: Showed left-sided lower abdominal pain
  • Carcinoembryonic antigen (CEA); 8.1 mg/L
  • Colonoscopy revealed a left-sided adenocarcinoma of the colon
  • Surgery: left hemicolectomy
  • Pathology: well-differentiated adenocarcinoma
  • PET/CT: 15/15 lymph nodes tested negative
  • Staging: IIIA
  • ECOG PS 0
  • Patient received adjuvant mFOLFOX4

April 2018

  • 24 months later, the patient complained of mild abdominal distension and his stools were pencil-shaped with some presence of blood
  • PET/CT scan showed widespread small liver lesions
  • CEA; 14.7 mg/L
  • Biopsy was CK2-positive
  • Molecular testing; allRAS&BRAFWT
  • ECOG PS 1
  • Patient began treatment with FOLFIRI + bevacizumab

February 2019

  • PET/CT scan showed evidence of new liver lesions and a 2-cm mass in the right lung
  • CEA; 31.7 mg/L
  • Patient started on regorafenib 80 mg/day