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Less-aggressive chemotherapy after initial treatment for metastatic CRC more beneficial

Fri, 12/20/2019 - 13:04
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A Mayo Clinic study involving 5,540 patients with metastatic colorectal cancer has reported that maintenance chemotherapy after initial treatment is more beneficial for patients whose disease is under control, compared with more aggressive treatment. The study, ‘The Role of Maintenance Strategies in Metastatic Colorectal Cancer - A Systematic Review and Network Meta-analysis of Randomized Clinical Trials’, was published in JAMA Oncology.

"Based on these findings, switching to a lighter, maintenance regimen of chemotherapy or even taking a break in treatment for some patients is appropriate, with reintroduction of full chemotherapy when the disease progresses," said the study's first author, Dr Mohamad Sonbol, a Mayo Clinic oncologist. "The goal of therapy in metastatic colorectal cancer is to prolong life while preserving or improving quality of life. As most of these therapies are associated with side effects, it's important to use treatments that achieve a maximum benefit with the fewest side effects.”

The authors noted that multiple randomised clinical trials have examined different strategies of continuing cytotoxic therapy until progression vs a period of either observation or the use of various maintenance agents. However, those studies have shown inconsistent efficacy results that make it challenging to draw any conclusion on which strategy is preferred. Therefore, the researchers undertook a meta-analysis to compare different treatment strategies for patients with metastatic colorectal cancer across randomised clinical trials.

Trials of interest included those including patients with metastatic colorectal cancer who were treated with an initial period of cytotoxic chemotherapy (with or without a biologic) and then switched to one of the following strategies: observation; maintenance with bevacizumab (Bev), fluoropyrimidine (FP), or both (FP + Bev); or continuing the induction regimen until progression. Outcomes of interest included overall survival (OS) and progression-free survival (PFS).

Twelve trials at low risk of bias (5,540 patients; age range, 23-85 years; 64.4 % male) were included in the network meta-analysis that showed no benefit of continuing full cytotoxic chemotherapy until progression vs observation in terms of PFS (hazard ratio, 0.71; 95% CI, 0.46-1.09) and OS (hazard ratio, 0.95; 95% CI, 0.85-1.07).

Compared with observation, maintenance therapy showed a PFS benefit (hazard ratio, 0.58; 95% CI, 0.43-0.77) but not an OS benefit (hazard ratio, 0.91; 95% CI, 0.83-1.01). All maintenance strategies (FP, FP + Bev, and Bev) showed significant improvement in PFS vs observation. On SUCRA analysis, maintenance treatment (FP or FP + Bev) had the highest likelihood of achieving improved PFS (67.1% for FP, 99.8% for FP + Bev, and 36.5% for Bev) and OS (81.3% for FP, 73.2% for FP + Bev, and 32.6% for Bev).

"Many chemotherapies that are used are initially beneficial in both shrinking and controlling the cancer," added Dr Tanios Bekaii-Saab, a Mayo Clinic gastrointestinal oncologist and the study's senior author. "However, after a few months of therapy, the maximum benefit is usually achieved and the main focus should be on how to continue that benefit while minimising side effects. This study confirms that switching to maintenance treatment is appropriate and beneficial, with introduction of full chemotherapy later upon progression of the disease."