SAN FRANCISCO – Adding bevacizumab to the FOLFOXIRI regimen significantly delayed the median time to progression of metastatic colorectal cancer to 12.2 months, compared with 9.7 months when bevacizumab was added to the FOLFIRI regimen, a phase III trial of 508 patients found.
Previous data had shown inferior progression-free survival, treatment response, and overall survival rates when treating metastatic colorectal cancer with FOLFIRI – which combines folinic acid (leucovorin), fluorouracil, and irinotecan – compared with FOLFOXIRI, which adds oxaliplatin to the drugs used in FOLFIRI.
Courtesy the American Society of Clinical Oncology
Dr. Fotios Loupakis
The current study confirms the superiority of first-line FOLFOXIRI over FOLFIRI and shows that FOLFOXIRI remains the better regimen when adding bevacizumab (Avastin) for select patients, Dr. Fotios Loupakis said at the annual Gastrointestinal Cancers Symposium sponsored by the American Society of Clinical Oncology.
At 2 years of follow-up, 20% of patients in the FOLFOXIRI/bevacizumab group and 11% in the FOLFIRI/bevacizumab group were free of disease progression, a significant difference, reported Dr. Loupakis of the University of Pisa (Italy) and his associates.
"Based on these results, FOLFOXIRI plus bevacizumab represents a new option for the treatment of metastatic colorectal cancer patients selected according to the eligibility criteria of this study," he said.
The multicenter study, known as the TRIBE trial, randomized adults in Italy aged 18-75 years who had unresectable metastatic colon cancer with histologically proven adenocarcinoma; at least one measurable lesion; and adequate bone marrow, liver, and renal functions. Patients younger than 71 years had to have an Eastern Cooperative Oncology Group performance status score of 0, and patients aged 71-75 years had a performance status score no higher than 2. Previous adjuvant chemotherapy containing oxaliplatin was allowed if more than 12 months had passed between the end of adjuvant therapy and the first relapse.
Subgroup analyses found better progression-free survival with FOLFOXIRI/bevacizumab in all subgroups.
Among secondary outcomes, the treatment response rate was significantly higher in the FOLFOXIRI/bevacizumab group (65%), compared with the FOLFIRI/bevacizumab group (53%), an intent-to-treat analysis showed.
Safety data on 504 patients revealed "moderately" increased rates of grade 3 or 4 diarrhea (19%), stomatitis (9%), and neutropenia (50%) in the FOLFOXIRI/bevacizumab group, compared with rates in the FOLFIRI/bevacizumab group (11% had diarrhea, 4% had stomatitis, and 20% had neutropenia), he said. The differences between groups in adverse events were statistically significant.
The two groups did not differ significantly, however, in the rate of grade 3 or 4 febrile neutropenia, the overall rate of serious adverse events, or the rate of treatment-related death. Nine percent of patients in the FOLFOXIRI/bevacizumab group developed grade 3 or 4 febrile neutropenia, compared with 6% of patients in the FOLFIRI/bevacizumab group. Serious adverse events were seen in 20% of each group, and approximately 2% in each group died of causes related to treatment.
Dr. Loupakis called the overall safety profile of FOLFOXIRI plus bevacizumab "acceptable." The study did not collect data on patients’ quality of life, he said.
Baseline demographics and disease characteristics were similar between groups.
The investigators are in the process of analyzing data on overall survival, secondary resections, treatment after disease progression, and potential biomarkers of response to treatment.
A previous phase II clinical trial of FOLFOXIRI plus bevacizumab had suggested promising results in terms of progression-free survival with acceptable toxicity, he said.
Dr. Loupakis has been a consultant for Bayer. Roche, which markets bevacizumab, provided support for the study. One of his associates in the study reported financial relationships with Roche, Amgen, Merck, and Sanofi.
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