Frontline FOLFOXIRI Plus Bevacizumab Improved PFS in mCRC: Phase 3 Trial Results

The following article features coverage from the American Society of Clinical Oncology 2019 meeting. Click here to read more of Cancer Therapy Advisor‘s conference coverage.

FOLFOXIRI plus bevacizumab may result in longer progression-free survival (PFS) than FOLFOX plus bevacizumab in patients with metastatic colorectal cancer (mCRC) with 3 or more baseline circulating tumor cells, suggested the results of an open, multicentric, randomized phase 3 trial presented at the 2019 American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago, Illinois.

Previous research has shown that FOLFOXIRI plus bevacizumab improved both PFS and overall survival (OS) in patients with metastatic colorectal cancer compared with FOLFIRI plus bevacizumab. However, the FOLFOXIRI-based schedule is not recommended for all patients due to its safety profile. Moreover, having 3 or more baseline circulating tumor cells has been linked to significantly shorter overall survival.

In the VISNU-1 trial (EU Clinical Trial Register Number: 2012-000846-37), 177 patients with mCRC were randomly assigned to receive FOLFOX plus bevacizumab and 172 patients with the condition were randomly assigned to receive FOLFOXIRI plus bevacizumab. The patients were scheduled to receive treatment every 2 weeks until disease progression, unacceptable toxicity, or withdrawal of informed consent. All patients were younger than 70 years. The primary end point of the study was PFS, while secondary end points included objective response rate and OS.

The researchers determined that the study met its primary end point, and the experimental treatment yielded a survival benefit. Among patients who received FOLFOXIRI plus bevacizumab, median PFS was 12.4 months compared with 9.3 months among those who received FOLFOX plus bevacizumab (log-rank P =.0006). Objective response rate among patients in the FOLFOXIRI-plus-bevacizumab arm was 59.0% compared with 52.0% in the FOLFOX-plus-bevacizumab arm (P =.1685).

Median follow-up was 50.7 months. OS among patients in the experimental treatment group was 22.3 months compared with 17.6 months in the FOLFOX-based group (log-rank P =.1407).

The authors noted that earlier data from the trial presented at ASCO 2018 showed that the FOLFOXIRI plus bevacizumab regimen had an acceptable toxicity profile.

“This is the first study performed in a population selected by baseline [circulating tumor cell] count,” said lead study author Javier Sastre, MD, PhD, a researcher with the Spanish Cooperative Group for the Treatment of Digestive Tumors and an oncologist at Hospital Clínico San Carlos in Madrid, Spain. “Our primary end point was met. Patients who received FOLFOXIRI plus bevacizumab had a statistically significant benefit for progression-free survival.”

Read more of Cancer Therapy Advisor‘s coverage of ASCO’s annual meeting by visiting the conference page.

References

1. Sastre J, Vieitez JM, Gomez-España MA, et al. Randomized phase III study comparing FOLFOX + bevacizumab versus folfoxiri + bevacizumab (BEV) as 1st line treatment in patients with metastatic colorectal cancer (mCRC) with ≥3 baseline circulating tumor cells (bCTCs). Presented at: 2019 American Society of Clinical Oncology (ASCO) Annual Meeting; May 31-June 4, 2019; Chicago, IL. Abstract 3507.
2. Loupakis F, Cremolini C, Masi G, et al. Initial therapy with FOLFOXIRI and bevacizumab for metastatic colorectal cancer. New Engl J Med. 2014; 371:1609-1618.
3. Cremolini C, Loupakis F, Antoniotti C, et al. FOLFOXIRI plus bevacizumab versus FOLFIRI plus bevacizumab as first-line treatment of patients with metastatic colorectal cancer: updated overall survival and molecular subgroup analyses of the open-label, phase 3 TRIBE study. Lancet. 2015;16(13):1306-1315.
4. Sastre J, Maestro ML, Gómez-España A. Circulating tumor cell count is a prognostic factor in metastatic colorectal cancer patients receiving first-line chemotherapy plus bevacizumab: a Spanish Cooperative Group for the Treatment of Digestive Tumors Study. Oncologist. 2012;17(7):947-955.
5. Gomez A, Vieitez JM, Gil S. Safety analysis of a phase III randomized trial comparing FOLFOX + bevacizumab vs FOLFOXIRI + bevacizumab as 1st line treatment in patients with metastatic colorectal cancer (mCRC) with ≥3 circulating tumor cells (CTCs) (VISNÚ-1 TTD TRIAL). J Clin Oncol. 2018;36(15_suppl):3536-3536.