Potential Case Outcomes for 65-Year-Old Man With mCRC

EP: 1.Overview: A 65-Year-Old Man with Metastatic Colorectal Cancer

EP: 2.First-Line Therapy Options for mCRC

EP: 3.Capecitabine/Bevacizumab and Signs of Progression/Recurrence for mCRC

EP: 4.Subsequent Lines of Therapy and Non-Chemotherapy Options for mCRC

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EP: 5.Potential Case Outcomes for 65-Year-Old Man With mCRC

Tanios Bekaii-Saab, MD, FACP: Regorafenib on this patient was started at 80 mg as part of ReDOS trial, and this was escalated to 120 and 160 mg. This patient seems to have tolerated it very well with minimal hand-and-foot syndrome reaction or fatigue. The patient was able to get to 160 mg and then went to cycle 2. Imaging did show cavitation in the lung lesions. We understand that these cavitations may be associated with a response, and the CEA [carcinoembryonic antigen] dropped significantly. Although there was no significant shrinkage, there was obviously cavitation and CEA response. This patient continued on 160 mg and did particularly well on 160 mg and continued for 9 months on regorafenib with no toxicities.

Unfortunately, at 9 months, this patient progressed and then ended up being switched to TAS-102 [tipiracil hydrochloride]. With TAS-102 [tipiracil hydrochloride], the patient had minimal toxicities but unfortunately did not seem to hold the response. Repeat scans did show multiple new lung metastases with more symptoms, as well as liver metastases that have grown. The patient showed some ascites. We had a discussion with the patient at the time about what to do next, and the performance status was relatively borderline. Liver functions were starting to rise significantly, and I couldn’t think about a good clinical trial for this patient, although at that point it was probably a phase 1 trial. We discussed this at length with the patient, and we came to the agreement that it would make the most sense for the patient to proceed with best supportive care and comfort care and move essentially to hospice care. The patient passed peacefully at home 3 months later.

The course of this patient unfortunately is not atypical. This patient went through close to 2 years of therapy. The KRAS mutation is certainly a negative prognostic factor. The presentation of the patient also shows a more aggressive disease or more aggressive biology, and overall those patients tend to have a shortened life span compared with those with RAS wild-type tumors who present less symptomatically. The course is not atypical.

One things I would have done different for this patient is I’ve moved a lot of my clinic to FOLFOXIRI [5-fluorouracil, leucovorin, oxaliplatin, irinotecan] plus bevacizumab, especially for a younger patient. The TRIBE2 data are very convincing in my mind. Especially with a KRAS mutation or the presence of a KRAS mutation, I feel compelled to go more aggressive. Does that change out from overall? It did appear that the survival outcome was better with those patients who went on the triplet vs the doublet and sequence with FOLFIRI [5-fluorouracil, leucovorin, irinotecan]. Although this was the secondary end point, the primary end point was met, and that’s certainly a thought. We tried to integrate a maintenance arm following 4 months of FOLFOXIRI [5-fluorouracil, leucovorin, oxaliplatin, irinotecan]. That makes it more palatable for the provider and the patient. I go for 3 months typically.

Overall, the course of this patient is a typical 1. My preference would have remained the same, and obviously he had a relatively decent outcome with regorafenib with stable disease for a few months. This case emphasizes multiple things. 1) The importance of screening colonoscopies. I’m not sure it would have changed much for this patient, but it’s important. You don’t want your first colonoscopy to be when you’re symptomatic at age 65. 2) The importance of getting molecular testing and getting it early. In this situation, unfortunately, this helped to exclude the EGFR inhibitors and give us some prognostic elements. But for many patients it can provide us with targets to go after. 3) Important to expose patients to all treatments that are active as eligible. There’s a point where treatment will induce more harm than benefit. We need to acknowledge that time, have a discussion with the patient, and make sure we shift the patient to the proper care.

In this situation, the patient has gone through all standard therapies from the chemotherapy: bevacizumab, regorafenib, and TAS-102 [tipiracil hydrochloride]. The regorafenib and TAS-102 [tipiracil hydrochloride] are similar in their activity. I favor regorafenib before TAS-102 [tipiracil hydrochloride], based on the data we published as well as the personal experience. But it’s also reasonable to do the opposite. I don’t foresee any studies that will look at 1 vs the other. The good news is this whole argument may become moot as we uncover more targets and we start including more targeted therapies and less of these target agnostic strategies.

The other thing is we’re seeing are promising data with TAS-102 [tipiracil hydrochloride] and bevacizumab. There’s a study that looks at TAS-102 [tipiracil hydrochloride] plus bevacizumab vs TAS-102 [tipiracil hydrochloride] that may confirm some of the early promising data and perhaps adds 1 option to our patients with TAS-102 [tipiracil hydrochloride] plus bevacizumab. We’ll see where that goes. Some data with regorafenib, and other multikinase inhibitors and immune therapy agents, primarily checkpoint inhibitors, have had mixed results and more toxicities. That activity is not as promising. There were hints in all the studies that perhaps for patients with nonliver metastases—metastases outside the liver—you may see better response but nothing really impressive. Overall, there remains challenges in this setting with unselected strategies.

This transcript has been edited for clarity.

Case:A 65-Year-Old Man With Metastatic Colorectal Cancer

Initial presentation

• A 65-year-old man reported a 2-month history of constipation, bloating, abdominal pain, and 10-pound unintentional weight loss
• PMH: Mild hypertension controlled with calcium channel blockers

Clinical workup

• Labs: Hg 9.4 g/dL, LFTs elevated and CEA 80 ng/mL
• Colonoscopy revealed a 5-cm completely obstructing mass in sigmoid colon
• Patient underwent left hemicolectomy with diverting ostomy
• Pathology: undifferentiated adenocarcinoma tumor invading through muscularis propria and extending into the pericolorectal tissue with5 of 12 resected nodes positive
• CT scan showed several lesions in both lobes of the liver, measuring up to 15 mm in diameter, and 3 small lesions (<5 mm) in the left lower pulmonary lobe
• Molecular testing: KRAS mutation in codon 12 of exon 2; microsatellite stable
• Diagnosis: Stage 4 colorectal cancer
• ECOG PS is 1
  
  

Treatment

• The patient received systemic therapy with FOLFOX + bevacizumab in the first line for 4 cycles
• The patient developed neuropathy and was switched to capecitabine + bevacizumab for 4 months and then unfortunately progressed, residual neuropathy at G1
• At that time he was switched to FOLFIRI + bevacizumab
• 6 months later, clinical progression is confirmed when new lung metastases are seen on chest CT
• The patient was switched to regorafenib