No Benefit to Continuing Full Induction Regimen Alone in Metastatic CRC

Investigators assert that there is no benefit to continuing a full induction regimen until progression without a period of observation or maintenance therapy in patients with metastatic colorectal cancer (CRC; JAMA Oncol. 2019 Dec 19. Epub ahead of print).

“Multiple randomized clinical trials have examined different strategies of continuing cytotoxic therapy until progression compared with a period of either observation or the use of various maintenance agents,” said Mohamad Bassam Sonbol, MD, Division of Hematology/Oncology, Mayo Clinic, Phoenix, Arizona, and colleagues.

“However, those randomized clinical trials have shown inconsistent efficacy results that make it challenging to draw any conclusion on which strategy is preferred,” they continued.

Thus, Dr Sonbol et al conducted a network meta-analysis to compare the efficacy of different treatment strategies for patients with metastatic CRC based on study data available via MEDLINE, Embase, Scopus, Web of Science, and the Cochrane Central Register of Controlled Trials.

The trials included were evaluating different strategies for treatment-naïve patients with metastatic CRC, including those treated with an initial period of cytotoxic chemotherapy (with or without a biologic) and then switched to observation; maintenance with bevacizumab, fluoropyrimidine, or fluoropyrimidine plus bevacizumab; or continuing the induction regimen until progression.

An initial analysis was performed on December 18, 2018, and outcomes of interest included overall survival (OS) and progression-free survival (PFS). The DerSimonian and Laird random-effects model was used to pool overall effect data, and a random-effects consistency model pooling evidence from direct and indirect comparisons was used to conduct a network meta-analysis. Furthermore, Dr Sonbol and co-investigators ranked the therapies using surface under the cumulative ranking (SUCRA) probabilities, with higher SUCRA scores corresponding to greater efficacy.

Ultimately, a network meta-analysis of 12 clinical trials with a low risk for bias that included 5540 patients (age, 23-85 years) demonstrated no benefit to continuing full cytotoxic chemotherapy until progression versus observation with regard to PFS (hazard ratio [HR], 0.71; 95% CI, 0.46-1.09) and OS (HR, 0.95; 95% CI, 0.85-1.07). In addition, although maintenance therapy demonstrated a benefit in PFS compared with observation (HR, 0.58; 95% CI, 0.43-0.77), the same was not reported for OS (HR, 0.91; 95% CI, 0.83-1.01).

Findings demonstrated significant improvements in PFS with all maintenance strategies (fluoropyrimidine, fluoropyrimidine plus bevacizumab, and bevacizumab) versus observation. In addition, maintenance therapy with fluoropyrimidine or fluoropyrimidine plus bevacizumab had the highest likelihood of achieving improved PFS (67.1% for fluoropyrimidine, 99.8% for fluoropyrimidine plus bevacizumab, and 36.5% for bevacizumab) and OS (81.3%, 73.2%, and 32.6%, respectively) per SUCRA analysis.

“For patients with metastatic colorectal cancer, there is no benefit to continuing the full induction regimen until progression, without a period of either observation or maintenance treatment,” Dr Sonbol and colleagues said.

“A maintenance strategy with a fluoropyrimidine, with or without the addition of bevacizumab, is preferred. However, given the lack of a clear OS benefit, shared decision-making should include observation as an acceptable alternative,” they concluded.—Hina Porcelli