Results from a review and meta-analysis support the use of maintenance after first-line therapy in patients with metastatic colorectal cancer.
The data showed that continuous induction did not confer a survival benefit over observation or maintenance therapy; however, maintenance improved progression-free survival (PFS), but not overall survival (OS), compared with observation. Furthermore, maintenance including a fluoropyrimidine, with or without bevacizumab, was most likely to improve survival.
These findings suggest maintenance may be appropriate for most patients with metastatic colorectal cancer, according to Mohamad Bassam Sonbol, MD, of Mayo Clinic in Phoenix and coauthors. Dr. Sonbol is the lead author of the review and meta-analysis, which was published in JAMA Oncology.
“For most patients, we are recommending a period of maintenance treatment,” Dr. Sonbol said in a JAMA Oncology podcast. “With the fluoropyrimidine, in most circumstances, we’re using capecitabine. Then, if cost is not an issue and toxicity is not an issue, we’re adding bevacizumab to this combination.”
Dr. Sonbol noted that certain patients, particularly those who have experienced a lot of toxicity, may do better with observation.
To reach these conclusions, Dr. Sonbol and colleagues analyzed data from 12 randomized phase 2 and 3 trials. Data from all 12 trials were included in the qualitative synthesis, but only 11 of the trials were included in the meta-analysis because of a lack of PFS and OS data from one trial.
In all, the data included 5,540 patients with previously untreated metastatic colorectal cancer. They ranged in age from 23 to 85 years, and most of them were male (64.4%).
For induction, patients received cytotoxic chemotherapy, with or without a biologic. For 10 trials, the induction regimen included oxaliplatin with either capecitabine or fluorouracil and leucovorin. Two trials included irinotecan-based induction.
In one trial, patients were managed with either continuous induction or observation. Continuous induction did not provide a PFS benefit (hazard ratio, 0.71; 95% confidence interval, 0.46-1.09) or an OS benefit (HR, 0.95; 95% CI, 0.85-1.07). In three trials, continuous induction was compared with maintenance. There was no PFS benefit (HR, 1.22; 95% CI, 0.84-1.78) or OS benefit (HR, 1.04; 95% CI, 0.92-1.17) with continuous induction over maintenance. There were six trials comparing maintenance to observation. Maintenance did provide a PFS benefit over observation (HR, 0.58; 95% CI, 0.43-0.77), but there was no OS benefit with maintenance (HR, 0.91; 95% CI, 0.83-1.01).
To compare maintenance regimens to one another, the researchers used surface under the cumulative ranking (SUCRA) probabilities. Higher SUCRA scores reflected greater efficacy.
Maintenance including a fluoropyrimidine, with or without bevacizumab, ranked higher than bevacizumab alone for both PFS and OS. The SUCRA values for PFS were 36.5% for bevacizumab, 67.1% for fluoropyrimidine, and 99.8% for fluoropyrimidine plus bevacizumab. The SUCRA values for OS were 32.6%, 81.3%, and 73.2%, respectively.
Dr. Sonbol and colleagues noted that this research is limited by the nature of meta-analyses (as compared with a prospective trial), a lack of blinding in some of the trials evaluated, and the use of study-level data rather than individual patient data.
Still, the researchers are recommending maintenance for most patients with metastatic colorectal cancer who achieve at least stable disease after induction. The team acknowledged that some patients may fare better with observation, and factors such as toxicity, cost, and patient preference should be considered when deciding on maintenance.
Dr. Sonbol did not disclose any conflicts of interest. Other authors disclosed relationships with multiple pharmaceutical companies.
SOURCE: Sonbol MB et al. JAMA Oncol. 2019 Dec 19. doi: 10.1001/jamaoncol.2019.4489.