Maintenance Therapies in Metastatic Colorectal Cancer
An oncologist reviews the maintenance therapy options in metastatic colorectal cancer and what clinical findings can lead to a change in therapies.
Kanwal Raghav, MBBS, MD: Maintenance therapy is a fairly common method that we apply in colorectal cancer, partly because the response from chemotherapy is pretty good in first-line treatment. Most patients will benefit from chemotherapy initially, but at some point, toxicities become limiting. This becomes more of an issue with oxaliplatin-based treatments than with irinotecan-based treatments.
There are multiple trials, such as CAIRO3, GERCOR OPTIMOX2, German CAO/ARO/AIO-04 study, and MRC COIN. All these studies dealt with maintenance therapy or continuous therapy vs intermittent therapy. There are 3 therapies. First is continuous therapy, which is continual chemotherapy till progression, full dose; intermittent therapy, where you stop treatment and then reintroduce treatment on progression; or maintenance therapy, where you decrease the intensity of chemotherapy from, say, a doublet or triplet cytotoxic to either bevacizumab–5-FU [5-fluorouracil] only, or 5-FU [5-fluorouracil] only, or bevacizumab only. These are maintenance therapies.
Our experience across these multiple trials, including our meta-analysis, has shown us that there’s no benefit to continuous therapy. There’s no benefit of doing chemotherapy all the way till progression. It appears that maintenance therapy is better than stopping all therapy altogether, especially with regard to progression-free survival. Although there’s a trend for overall survival benefit, this has not proven to be statistically significant in most of these trials, including the meta-analysis. We routinely perform and advocate for maintenance therapy. In the meta-analysis, we’ve also shown that the highest likelihood of benefit of PFS [progression-free survival] came from using the combination of bevacizumab and 5-FU [5-fluorouracil] rather than 5-FU [5-fluorouracil] or bevacizumab alone. In our practice, we generally tend to use a combination of bevacizumab and 5-FU [5-fluorouracil]. However, using bevacizumab is reasonable. In the German CAO/ARO/AIO-04 study, bevacizumab was no worse than the combination of bevacizumab and 5-FU [5-fluorouracil]. Clearly, there are more toxicities in a continuous therapy than in intermittent or maintenance treatment. Therefore, this is a very reasonable option.
As a general rule, we usually adopt maintenance strategy in patients with colorectal cancer, but there are a select group of patients for whom a chemotherapy break is completely reasonable. These are patients who have lower-volume disease; patients who had a really good response to chemotherapy otherwise. In some cases, there are patients for whom, during the induction chemotherapy, quality of life is adversely affected because of the toxicities of chemotherapy or because of the way we do this chemotherapy every 2 weeks or so. In those patients, we have generally adopted a chemotherapy-break approach. The only caution with a chemotherapy-break approach is to keep a close eye on the patient, clinically as well as from a tumor marker and blood work perspective. We usually scan these patients every 2 to 3 months. There are some cases in which I wouldn’t adopt a maintenance strategy, such as patients who have large-volume disease or peritoneal disease, where a small amount of progression can result in some sort of visceral crisis. There, I would adopt a maintenance strategy approach.
We look at all 3 factors: radiographic findings, tumor markers, patterns in which the tumor markers and radiographic findings are correlated with one another or with the treatment of the patient. We also look at clinical symptoms. There’s just not 1 particular factor that we concentrate on more over the other. It’s more the complete picture that tells us whether the patient is responding or not responding. Add to it the fact that toxicity and quality of life are equally important factors because you could be responding, but if you’re not tolerating chemotherapy well, then those are not the kind of patients you want to continue that same chemotherapy regimen for. It’s a compendium of factors rather than 1 single factor in and of itself.
Overall, starting with the first-line therapy, we usually use a biologic with chemotherapy. If you use a doublet, then it gives you an option of continuing with another biologic and chemotherapy in second line. The distinction between lines of therapy has blurred a little in recent times because molecular profiling has come into the picture. Patients with BRAF mutations are often treated with the BEACON CRC regimen, which is a combination of an anti-EGFR and a BRAF inhibitor. Patients who have HER2-amplified tumors have the option of receiving HER2-directed therapy, especially dual anti-HER2 therapy, such as trastuzumab-pertuzumab, trastuzumab-lapatinib, or trastuzumab-tucatinib.
We also have options for immunotherapy if you have not used it in first line for MSI [microsatellite instability]–high tumors. The efficacy is pretty good in second and third lines. If possible, all the MSI-high patients should get I/O [immuno-oncology] up front. But as far as third-line options are concerned, we have 2 major drugs that are standard of care. One of them is regorafenib, the other 1 is TAS-102 [tipiracil hydrochloride]. Not to mention that patients who have NTRK fusions can get NTRK inhibitors. Those are the general guidelines that you use for second- or third-line therapy.
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
Phase 3 Trials of Botensilimab/Balstilimab Move Forward, Despite FDA's Approval Setback
July 18th 2024Agenus was advised by the FDA against filing for accelerated approval of botensilimab plus balstilimab for relapsed/refractory microsatellite stable metastatic colorectal cancer without liver metastases.
Read More
