• Gastrointestinal Cancers
• Oncology Clinical Trials

• Gastrointestinal Cancers
• Oncology
• Oncology Clinical Trials

The optimal duration of treatment with fluoropyrimidines (FPs), oxaliplatin (OX), and bevacizumab (BEV) for patients with metastatic colorectal cancer (mCRC) is not known. Susanna Hegewisch-Becker, MD, Onkologische Schwerpunktpraxis Eppendorf, Hamburg, Germany, presented results from the phase 3 study Optimal Maintenance Therapy With Bevacizumab After Induction in Metastatic Colorectal Cancer (CRC) [AIO KRK 0207; NCT00973609]. This trial investigated maintenance chemotherapy with FPs + BEV, BEV alone, or no treatment following a 24-week first-line induction with FPs, OX, and BEV for patients with mCRC.

Patients with at least stable disease (SD) after induction therapy were randomly assigned to FPs (any standard regimen that includes an FP, eg, FOLFOX4) plus BEV (n = 158), BEV alone (n = 156), or no therapy (n = 158). At first progression, patients received reinduction therapy with any FP with or without either BEV or OX until second progression occurred. The primary end point was the time to failure of strategy (TFS), including maintenance plus reinduction after first progression. Secondary end points included time to first progression (PFS-1), overall survival (OS), quality of life (QOL), and biomarker studies.

All 3 arms appeared well balanced for baseline characteristics. Median TFS from randomization for all patients was 6.4 months. Median PSF-1 for all patients from randomization was 4.6 months. Updated outcome results are summarized in Table 1.

There was no significant difference in TFS between FPs + BEV and BEV (HR, 1.03; 95% CI, 0.81 to 1.31; P = .82) or between FPs + BEV and no therapy (HR, 1.27; 95% CI, 1.0 to 1.62; P = .054). There was no significant difference in PFS-1 between FPs + BEV and BEV (HR, 1.26; 95% CI, 0.99 to 1.60; P = .061); however, there were significant differences in PFS-1 between FPs + BEV and no therapy (HR, 2.05; 95% CI. 1.61 to 2.63; P < .00001) and BEV versus no therapy (HR, 1.53; 95% CI, 1.21 to 1.93; P = .00039).

There was no significant difference among groups for OS, which may be because not enough events occurred and because of the use of new further-line therapies at progression that became available during the study. Dose reductions or discontinuations of OX during induction did not appear to affect PFS-1 or OS.

The best response at induction had a prognostic effect on OS. Median OS was 24 months for patients with complete response or partial response, whereas OS was 19.8 months for patients with SD. There were no differences across treatment arms for OS or PFS-1 when stratified for best response at induction.

Patients with wild-type tumors treated with BEV had a PFS-1 of 6.8 versus 3.9 months for no therapy (P < .001). For any mutation with a poorer prognosis, there was no significant difference for BEV versus no treatment (4.2 vs 3.6 months, P = .17). Subgroup analysis of OS did not identify patient groups with more or less benefit from FPs + BEV. Results of QOL studies indicated that active treatment did not reduce QOL, and a lack of therapy did not cause fear of progression.

This study confirms the use of active maintenance treatment as standard of care for most patients to improve PFS-1. The lack of a clear OS benefit suggests that an individualized approach to active maintenance therapy may be appropriate.

• © 2014 MD Conference Express®