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Combining Newer, More Intensive First-Line Chemotherapy With Bevacizumab Improves Long-Term Outcome in Advanced Colorectal Cancer

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Key Points

  • The median overall survival was significantly improved in the FOLFOXIRI-plus-bevacizumab group compared to the FOLFIRI-plus-bevacizumab group,
  • Patients in the FOLFOXIRI had a 5-year overall survival of 24.9% compared to 12.4% in the FOLFIRI group.
  • FOLFOXIRI is an intensive regimen and should not be given to patients older than 75 and those between 70 and 75 who are not in good general condition.

Updated results from TRIBE, an Italian phase III study of patients with metastatic colorectal cancer, indicate that FOLFOXIRI (leucovorin, fluorouracil [5-FU], oxaliplatin, irinotecan) chemotherapy in combination with bevacizumab (Avastin) is superior to the standard FOLFIRI (leucovorin, 5-FU, irinotecan) chemotherapy with bevacizumab. Compared to the FOLFIRI combination regimen with bevacizumab, the FOLFOXIRI-plus-bevacizumab regimen extended overall survival by about 4 months and doubled the 5-year overall survival rate. 

The study confirms findings from the previous, smaller phase III GONO study, which showed that FOLFOXIRI alone improved survival compared with FOLFIRI alone in the first-line treatment of metastatic colorectal cancer. The results were reported in advance of the 2015 Gastrointestinal Cancers Symposium, to be held January 15 to 17 in San Francisco (Abstract 657).

“This new approach offers a substantial survival improvement, even for patients with a rather unfavorable prognosis. This is a remarkable step forward in the treatment of this disease,” said presenting author Chiara Cremolini, MD, a medical oncologist at the Tuscan Tumor Institute in Pisa, Italy. “We believe that our results will encourage clinicians to adopt the FOLFOXIRI regimen with bevacizumab as an upfront therapy option for patients in otherwise good health.”

TRIBE Study

In the study, 508 patients with metastatic colorectal cancer were randomly assigned to induction therapy consisting of FOLFIRI plus bevacizumab or FOLFOXIRI plus bevacizumab. Up to 6 months (12 cycles) of induction therapy were planned, followed by maintenance treatment with bevacizumab in combination with less intensive chemotherapy, 5-FU, until the disease progressed. In about 80% of the patients, the cancer was not confined to the liver, and surgery was not feasible in most of them. Similar numbers of patients in both groups (15% in the FOLFOXIRI-plus-bevacizumab group, 12% in the FOLFIRI-plus-bevacizumab group) were able to undergo radical resection after the induction therapy shrunk their tumors.

Patients were followed for a median period of 48.1 months. The median overall survival was significantly improved in the FOLFOXIRI-plus-bevacizumab group compared to the FOLFIRI-plus-bevacizumab group (29.8 vs 25.8 months). One out of four patients (24.9%) in the FOLFOXIRI group were estimated to be alive 5 years after starting treatment, compared with one out of eight patients (12.4%) in the FOLFIRI group.

While FOLFOXIRI increased the risks of diarrhea and low blood counts compared to FOLFIRI, serious adverse events were not increased. Dr. Cremolini noted that, while many patients are able to tolerate FOLFOXIRI, it is an intensive regimen and should not be given to all patients, such as those older than 75 and those between 70 and 75 who are not in good general condition.

“The doubling in the percent of patients alive 5 years after diagnosis is important and intriguing. For patients who can tolerate a combination of three chemotherapy drugs, the FOLFOXIRI-plus-bevacizumab regimen is an important treatment advance,” said Smitha S. Krishnamurthi, MD, moderator of today’s presscast and ASCO expert. 

Phase III Trial Underway

TRIBE-2, the follow-on phase III trial to the current study, is being launched in Italy by the GONO group. Six hundred and fifty-four patients will be randomly assigned to receive first-line FOLFOXIRI plus bevacizumab followed by either reintroduction of FOLFOXIRI plus bevacizumab at disease progression or FOLFOX plus bevacizumab followed by FOLFIRI plus bevacizumab at progression.

Ongoing phase II trials, named MACBETH and MOMA, are exploring strategies to shorten the duration of initial chemotherapy (from 6 to 4 months) and improve efficacy of the maintenance treatment. In the MACBETH study FOLFOXIRI is being tested in combination with the EGFR inhibitor cetuximab (Erbitux), which works differently than bevacizumab

The study was supported by the Gruppo Oncologico Nord Ovest (GONO) and the ARCO Foundation. A research grant was provided by F. Hoffmann–La Roche.

For full disclosures of the study authors, view the study abstract at abstract.asco.org.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


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