Review of Maintenance Treatment in mCRC Highlights Need for Shared Decision Making

A study published in JAMA Oncology found that administration of continued full cytotoxic chemotherapy until patients with metastatic colorectal cancer (mCRC) experience progression, without a period of observation or maintenance treatment, derived no benefit.

Moreover, the study found that maintenance strategy with fluoropyrimidine, either with or without the addition of bevacizumab (Avastin), was preferred.

“Although a maintenance strategy with a fluoropyrimidine with or without bevacizumab is preferred over continuous induction therapy for metastatic colorectal cancer, shared decision-making should include observation as an acceptable option, given the lack of significant overall survival benefits,” the researchers wrote.

In this systematic review and network meta-analysis of 12 randomized clinical trials, data from a total of 5,540 patients ranged 23-85 years showed no benefit to continuing the full induction regimen in terms of progression-free survival (PFS; hazard ratio [HR], 0.71; 95% CI, 0.46-1.09) and overall survival (OS; HR, 0.95; 95% CI, 0.85-1.07). When the authors compared observation with maintenance therapy, a benefit in PFS was seen (HR, 0.58; 95% CI, 0.43-0.77) while no benefit in OS was shown (HR, 0.91; 95% CI, 0.83-1.01).

“In this study, we confirm that maintenance therapy and even a cessation of treatment are acceptable options vs continuing the full regimen,” noted the authors. “A clear advantage for deescalating treatment after achieving a maximum response (typically 3-4 months) with induction therapy includes minimizing toxic effects, maximizing quality of life, and likely improving cost.”

The primary outcomes analyzed by the study were PFS and OS. Of the 12 trials that were analyzed, 7 had observation as the control group, 3 with bevacizumab alone, 2 with fluoropyrimidine alone, and 2 fluoropyrimidine with fluoropyrimidine plus bevacizumab. One study examined the continuation of full induction of chemotherapy until progression with observation, while 3 looked at continuing the full regimen until progression compared with maintenance therapy.

The PFS benefit derived from maintenance therapy versus observation alone was shown across all therapies, with fluoropyrimidine plus bevacizumab having the highest likelihood of achieving improved PFS (fluoropyrimidine plus bevacizumab, 99.8%; fluoropyrimidine, 67.1%; bevacizumab, 36.5%).

While the maintenance therapy with fluoropyrimidine was shown to be the preferred option for PFS, the lack of significant benefits in OS led the authors to conclude that observation alone is an acceptable option.

“Overall, (fluoropyrimidine) as monotherapy or combined with (bevacizumab) seems to be the preferred maintenance strategy,” the authors wrote. “Because the added value of (bevacizumab) is unclear in the maintenance setting, the choice for adding it to (fluoropyrimidine) will depend on many factors, including patient preferences, risk of toxic effects, and added cost.”

The authors noted a couple of limitations to the study, in particular that only 2 of the trials they analyzed clearly stated blinding of the outcome assessors. Additionally, the analysis was performed with study-level data, rather than patient data, which perhaps limited the power of their analysis.

“Despite these limitations, we believe our study is the most comprehensive and up-to-date analysis of maintenance strategies in mCRC,” noted the authors before adding “Optimal maintenance strategies should be dependent on factors such as patient preference, cost of care, and potential toxic effects.”

Reference:

Sonbol MB, Mountjoy LJ, Firwana B, et al. The Role of Maintenance Strategies in Metastatic Colorectal Cancer: A Systematic Review and Network Meta-Analysis of Randomized Clinical Trials. JAMA Oncol. doi: 10.1001/jamaoncol.2019.4489. [Epub ahead of print]