Maintenance Therapy for mCRC

Tanios Bekaii-Saab, MD, FACP:The patient did very well on the FOLFOX/bevacizumab. He had a first CT scan a couple of months after starting treatment, which showed a partial response—the tumors were shrinking already. And then, he had another CT scan at 4 months, which showed further response. The patient was staring to develop a little lower toxicity. Nothing really major, he was still functional. So, the decision was appropriate to move him to the maintenance setting with capecitabine and bevacizumab. And this is now February 2017. The patient has been continuously on capecitabine/bevacizumab with occasional breaks here and there, but mostly, he’s been on capecitabine/bevacizumab maintenance for about 22 months and continuously showing disease control and good quality of life. The patient’s doing well, is active, has good appetite, is maintaining his weight, so he is doing great.

When we look at all of our patients with metastatic colon cancer, the traditional wisdom is used to dictate that we treat those patients to progression, and that makes sense. The problem is if you go with FOLFOX, or even with FOLFIRI, for more than 3 to 4 months, the patients will start having significant toxicities with oxaliplatin—neuropathy, fatigue, and splenomegaly issues, injuries to the liver, etc—in the long run. So, we have to be very careful and very judicious about when to stop.

With irinotecan after 6 months, patients get quite fatigued. There is also liver injury. Irinotecan has the advantage of never having cumulative neurotoxicity, which certainly is a plus, but nonetheless whether it’s FOLFIRI or FOLFOX, we know we have a time to stop. The question that comes thereafter is, if you stop the chemotherapy, do you continue on some form of maintenance therapy or not? That question has been asked multiple ways through a number of phase III randomized studies. And the answer that always comes out is that it makes sense to continue some form of maintenance therapy, typically 5-FU or capecitabine. The CAIRO3 study looked at maintenance capecitabine—lower dose, continuous—with bevacizumab. There was an advantage in terms of the progression-free survival, disease-free survival at 1 or 2 intervals and even a hint that we may improve survival of patients versus stopping.

So, I think it’s very important to consider patients for maintenance therapy with low-dose continuous capecitabine. I tend to do Monday through Friday, then skip the weekends for those patients, especially on the long run. My patients, at 2 to 3 years, start having some hand and foot syndrome and issues. I actually give them those 2 days’ break. Believe it or not, it actually makes a big difference. That’s one way to do it. And the bevacizumab is continuous.

Now some folks ask the question about, can we just do bevacizumab without capecitabine? And the answer is no. It doesn’t seem that bevacizumab on its own without the fluoropyrimidine makes a difference in terms of the maintenance. I think it has to be fluoropyrimidine and bevacizumab. Then, the next question is, is there ever a situation where you would actually not give any more chemotherapy, meaning you tell the patient, “OK, you got a break”? The answer is clearly yes. Patients get tired, even when going on maintenance therapy. They are coming every 3 weeks, they’re getting an injection. Capecitabine is not benign. It has its own toxicities, and patients, frankly, get tired from just coming to the cancer center and to the doctor all the time. They want to live their lives, and that’s what we want to try to achieve. In many instances, we actually do make a decision—after a certain while, say 1 to 2 years, and things have been continuously going great—to just forgo the chemotherapy and just observe them. I think that’s very acceptable.

There are also some instances where patients choose from the get-go to stop after 4 to 6 months and be done. Again, it’s a patient preference. As long as the physician is able to sit with the patient and have the opportunity to discuss the pros and cons of all this, I think it’s very acceptable either way.

Transcript edited for clarity.

November 2012

• A 51-year-old man was referred to gastroenterology for screening colonoscopy.
• Family history includes pancreatic cancer on his father’s side and pre-menopausal breast cancer in his aunt.
• Colonoscopy revealed a 3-cm mass, proximal to the hepatic flexure.
• Biopsy confirmed the lesion to be of adenocarcinoma histology.
• At the time, the patient underwent right hemicolectomy revealing a moderately differentiated tumor. Fifteen lymph nodes were removed and tested negative for metastatic disease, denoting stage T3N0M0 colon cancer.
• The patient healed without complications and received no further treatment.

April 2015

• The patient continued to feel well, except for occasional fatigue and diarrhea.
• Routine evaluation showed elevated carcinoembryonic antigen.
• PET/CT scan revealed several small lesions in multiple lobes of the liver that were PET avid
• Biopsy was performed and confirmed the liver lesions to be metastases from colon cancer
• The patient was referred to a local oncologist and started on infusional 5-FU and oxaliplatin (FOLFOX) in combination with bevacizumab.
• CT scan 2 months after starting treatment showed a partial response to therapy; at 4 months the patients tumor continued to shrink
• Oxaliplatin was discontinued; subsequently the patient received maintenance therapy with capecitabine and bevacizumab, resulting in continued disease control

February 27, 2017

• The patient has had stable disease for 22 months and remains on bevacizumab maintenance therapy.
• He appears generally well and free of symptoms.