Optimal Treatment of Chemoresistant mCRC - Episode 1

A 60-Year-Old Male with Relapsed mCRC

March 13, 2019

Tanios Bekaii-Saab, MD, FACP:April 2015, this man, 60-year-old, presents to his primary care physician with complaints of some fatigue, some weight loss. Primarily though, changes in the bowel movements and some blood in the stools. A workup follows, including a colonoscopy which shows a mass on the right side of the colon which was biopsied, then shows evidence of adenocarcinoma consistent with a colonic primary. The patient was staged. There was no evidence of any other disease. He was sent to the surgeon at that time, underwent laparoscopic right hemicolectomy, and he was staged at IIIA. So that’s low-risk colon cancer with essentially a decision that followed to proceed with adjuvant chemotherapy. And based on the IDEA trial, the decision was to proceed with 3 months of capecitabine plus oxaliplatin, followed by close observation as per routine. The patient did fine with the capecitabine and oxaliplatin or the Capox with grade 1 neuropathy, relatively tolerable, very low hand and foot syndrome, but no major toxicities.

Thirty months later, that’s April 2018, the patient started having some symptoms of abdominal pain, again some fatigue, some weight loss. Over 2, 3 months he lost about 10 pounds or so. The patient was overall not feeling well, so there was a concern that this could essentially be an element of progressive disease. He was scanned at this time. PET/CT shows evidence of both liver and lung metastases. To confirm the diagnosis since about 30 months have elapsed from the end of his adjuvant chemotherapy, a decision was to biopsy one of those liver lesions. Indeed, a biopsy suggested an adenocarcinoma which was consistent with colon cancer. His CEA [carcinoembryonic antigen] was on the rise at that time. Additional sequencing genomic sequencing suggests microsatellite stable tumor,RASwild-type andBRAFwild-type. So molecular testing was performed showing evidence ofRASwild-type,BRAFwild-type, microsatellite stable, andHER2nonamplified.

The patient’s ECOG [The Eastern Cooperative Oncology Group] performance status was 1, a little bit less than 1, still relatively active doing things, moving around. Patient is relatively symptomatic right-sided tumor, so the decision at that time was to start the patient on Folfoxiri plus bevacizumab, given the symptoms, given relatively a younger individual at now 62, 63. And then the goal was to expose the patient to about 2 to 3 months of Folfoxiri/bevacizumab and then transition to maintenance therapy.

The patient proceeded with 6 cycles of Folfoxiri/bevacizumab, almost complete resolution of the symptoms, getting closer to grade 2 neuropathy, I think some of the cumulative neuropathy from oxaliplatin and with the FOLFOXIRI. The PET/CT at that time showed near complete resolution of his lung and liver metastases with a dip in his CEA. At that time, we dropped oxaliplatin, continued with Folfiri for another 6 cycles, checked scans. Scans continued to look great. At that time, some fatigue, some elements of toxicity related to the chemotherapy—diarrhea, and others led to stopping the irinotecan and the 5-FU [fluorouracil], continued the Avastin, although moving this to every 3 weeks, and then the patient was switched to oral maintenance chemotherapy with capecitabine, so capecitabine/bevacizumab, bevacizumab every 3 weeks, capecitabine daily, 5 days a week, Monday to Friday and then weekends off.

The patient did extremely well with the treatment for about 2 cycles and then started developing symptoms again—fatigue, abdominal pain. His neuropathy was still grade 1 at this point. It actually went down from grade 2 to grade 1, but it was a grade 1 bordering on grade 2. And then the decision at that time was that this is a patient that remained with significant neuropathy, progressed within 2 months of stopping FOLFIRI on maintenance therapy, so it was time to switch to a new therapy.

Now, this is a right-sided tumor, so we understand that options are relatively limited. Decision at that time after discussions with the patient was to proceed with regorafenib, starting with a dose of 80 mg orally every day for the first week, with a goal to dose escalate 40 mg per week orally until we reach 160 mg within 3 weeks if there are no significant toxicities related to the regorafenib.

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