Dataset Information

Continuing single-agent bevacizumab as maintenance therapy after induction XELOX (or FOLFOX) plus bevacizumab in first-line treatment of metastatic colorectal cancer.

ABSTRACT: Metastatic colorectal cancer is the second leading cause of cancer death in the United States. Since 1995, treatment regimens have included capecitabine, irinotecan, oxaliplatin, bevacizumab, cetuximab, panitumumab, aflibercept, and reforafenib. These medications have doubled the median survival of patients and improved the 5-year survival from less than 1% to 20%. Approximately 75% of patients stop first-line chemotherapy in clinical trials for reasons other than progressive disease and face the question of whether to consider "maintenance" chemotherapy or take a chemotherapy break. In this challenging case, Drs. Díaz-Rubio, Pietrantonio, and de Braud reflect on the data and offer their opinions. If each of the nearly 40,000 patients in the U.S. who face this decision chooses bevacizumab, the total cost is approximately $240 million per dose ($6,000 per infusion). The importance of this question and the cost to society are enormous.

SUBMITTER: Diaz-Rubio E

PROVIDER: S-EPMC3500363 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature

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Continuing single-agent bevacizumab as maintenance therapy after induction XELOX (or FOLFOX) plus bevacizumab in first-line treatment of metastatic colorectal cancer.

Díaz-Rubio Eduardo E Pietrantonio Filippo F de Braud Filippo F

The oncologist 20121016 11

Metastatic colorectal cancer is the second leading cause of cancer death in the United States. Since 1995, treatment regimens have included capecitabine, irinotecan, oxaliplatin, bevacizumab, cetuximab, panitumumab, aflibercept, and reforafenib. These medications have doubled the median survival of patients and improved the 5-year survival from less than 1% to 20%. Approximately 75% of patients stop first-line chemotherapy in clinical trials for reasons other than progressive disease and face th ...[more]

PMID: 23073991

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Project description:BackgroundDysregulated hepatocyte growth factor/mesenchymal-epithelial transition (MET) signaling is associated with poor prognosis and resistance to vascular endothelial growth factor inhibition in metastatic colorectal cancer (mCRC). We report outcomes from a double-blind, multicenter phase II trial of the MET inhibitor onartuzumab in combination with mFOLFOX-6 and bevacizumab for mCRC (GO27827; NCT01418222).Materials and methodsPatients were randomized 1:1 to receive onartuzumab (10 mg/kg intravenously [IV]) or placebo plus mFOLFOX-6 and bevacizumab (5 mg/kg IV). Oxaliplatin was given for 8-12 cycles; other agents were continued until disease progression, unacceptable toxicity, or death. The primary endpoint was progression-free survival (PFS) in the intent-to-treat (ITT) and MET immunohistochemistry (IHC) expression-positive populations.ResultsBetween September 2011 and November 2012, 194 patients were enrolled. In September 2013, an interim analysis recommended stopping onartuzumab treatment due to lack of efficacy. At the time of the final analysis in February 2014, no significant improvement in PFS was seen with onartuzumab versus placebo in either the ITT or MET IHC-positive populations. An improvement in PFS was noted in the MET IHC-negative population. Neither overall survival nor response rate was improved with onartuzumab. The incidence of fatigue, peripheral edema, and deep vein thrombosis was increased with onartuzumab relative to placebo.ConclusionOnartuzumab combined with mFOLFOX-6 and bevacizumab did not significantly improve efficacy outcomes in either the ITT or MET IHC-positive populations. MET expression by IHC was not a predictive biomarker in this setting. The Oncologist 2017;22:264-271 IMPLICATIONS FOR PRACTICE: The addition of onartuzumab to mFOLFOX-6 plus bevacizumab did not improve outcomes in patients with previously untreated metastatic colorectal cancer in this randomized, phase II study. Although initial results with onartuzumab were promising, a number of phase II/III clinical trials have reported a lack of improvement in efficacy with onartuzumab combined with standard-of-care therapies in several tumor types. Furthermore, negative study data have been published for rilotumumab and ficlatuzumab, both of which block hepatocyte growth factor binding to the mesenchymal-epithelial transition (MET) receptor. MET immunohistochemistry was not a predictive biomarker. It remains to be seen if other biomarkers or small molecule inhibitors may be more appropriate for inhibiting this oncogenic pathway.

Dataset Information

Continuing single-agent bevacizumab as maintenance therapy after induction XELOX (or FOLFOX) plus bevacizumab in first-line treatment of metastatic colorectal cancer.

Publications

Continuing single-agent bevacizumab as maintenance therapy after induction XELOX (or FOLFOX) plus bevacizumab in first-line treatment of metastatic colorectal cancer.

Similar Datasets

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