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Maintenance Therapy for Colorectal Cancer: Which Regimen and Which Patients?

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Abstract

The introduction of therapeutic agents such as irinotecan, oxaliplatin, and more recently biologic agents such as vascular endothelial growth factor and epidermal growth factor receptor (EGFR) inhibitors has significantly improved survival of patients with metastatic colorectal cancer. These novel agents have also contributed to added toxicities. Therefore, several studies have evaluated the role of maintenance therapy with less intensive regimens in patients who experienced stable disease or treatment response following induction therapy as a strategy to reduce toxicity and improve quality of life. The success of such strategies, however, requires assurance that their survival would not be compromised. We therefore reviewed studies that have explored the various strategies of treatment de-escalation with an emphasis on survival and toxicity outcomes. Recent studies evaluated the role of maintenance therapy with chemotherapy only, chemotherapy plus bevcizumab, bevacizumab only, and EGFR inhibitors. Current evidence suggests that maintenance strategies offer significant benefit to patients by providing continuous clinical benefit while minimizing the risks associated with continuous therapy. Strategies to improve selection of patients for maintenance therapy versus identifying subgroups of patients that will benefit from a chemotherapy-free interval need to continue to be studied. Finally, as our understanding of the molecular and genetic drivers of colorectal cancer continues to expand, refining these strategies to include more target-specific agents should become more routine.

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Authors and Affiliations

  1. The Ohio State University-James Cancer Hospital and Richard Solove Research Institute, 320 W. 10th Avenue, Columbus, OH, 43221, USA

    Sameh Mikhail & Tanios Bekaii-Saab

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  1. Sameh Mikhail
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  2. Tanios Bekaii-Saab
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Correspondence to Tanios Bekaii-Saab.

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Tanios Bekaii-Saab: consulting fees from Genenteach, BMS, Amgen, Taiho, Bayer. Fees for participation in review activities: Polaris, exel exis. Sameh Mikhail has no conflicts to declare.

Appendix: Trial acronyms

Appendix: Trial acronyms

OPTIMOX 1

OPTIMOX1: a randomized study of FOLFOX4 or FOLFOX7 with oxaliplatin in a stop-and-Go fashion in advanced colorectal cancer—a GERCOR study

OPTIMOX2

Can chemotherapy be discontinued in unresectable metastatic colorectal cancer? The GERCOR OPTIMOX2 Study

CONcePT

Improved time to treatment failure with an intermittent oxaliplatin strategy: results of CONcePT

STOP and GO trial

Bevacizumab + capecitabine as maintenance therapy after initial bevacizumab + XELOX treatment in previously untreated patients with metastatic colorectal cancer: phase III ‘Stop and Go’ study results—a Turkish Oncology Group Trial

CAIRO3

Final results and subgroup analyses of the phase 3 CAIRO3 study: maintenance treatment with capecitabine + bevacizumab versus observation after induction treatment with chemotherapy + bevacizumab in metastatic colorectal cancer (mCRC)

AIO KRK 0207

Maintenance strategy with fluoropyrimidines (FP) plus Bevacizumab (Bev), Bev alone, or no treatment, following a standard combination of FP, oxaliplatin (Ox), and Bev as first-line treatment for patients with metastatic colorectal cancer (mCRC): a phase III non-inferiority trial (AIO KRK 0207)

MACRO-TTD study

First-line XELOX plus bevacizumab followed by XELOX plus bevacizumab or single-agent bevacizumab as maintenance therapy in patients with metastatic colorectal cancer: the phase III MACRO TTD study

SAKK 4106

Bevacizumab continuation versus no continuation after first-line chemotherapy plus bevacizumab in patients with metastatic colorectal cancer: a randomized phase III non-inferiority trial (SAKK 41/06)

NORDIC ACT

A randomized phase III trial on maintenance treatment with bevacizumab alone or in combination with erlotinib after chemotherapy and bevacizumab in metastatic colorectal cancer: the Nordic ACT Trial

NORDIC VII

Phase III trial of cetuximab with continuous or intermittent fluorouracil, leucovorin, and oxaliplatin (Nordic FLOX) versus FLOX alone in first-line treatment of metastatic colorectal cancer: the NORDIC-VII study

COIN-B

Intermittent chemotherapy plus either intermittent or continuous cetuximab for first-line treatment of patients with KRAS wild-type advanced colorectal cancer (COIN-B): a randomised phase 2 trial

COIN

Intermittent versus continuous oxaliplatin and fluoropyrimidine combination chemotherapy for first-line treatment of advanced colorectal cancer: results of the randomised phase 3 MRC COIN trial

PRODIGE 9

FOLFIRI + bevacizumab induction chemotherapy followed by bevacizumab or observation in metastatic colorectal cancer, a phase III trial (PRODIGE 9-FFCD 0802)

PRIME study

Randomized, phase III trial of panitumumab with infusional fluorouracil, leucovorin, and oxaliplatin (FOLFOX4) versus FOLFOX4 alone as first-line treatment in patients with previously untreated metastatic colorectal cancer: the PRIME study

PEAK study

A randomized phase II study of mFOLFOX6 with either panitumumab (pmab) or bevacizumab (bev) as first-line treatment (tx) in patients (pts) with unresectable wild-type (WT) KRAS metastatic colorectal cancer (mCRC)

DREAM

Bevacizumab-erlotinib as maintenance therapy in metastatic colorectal cancer. Final results of the gercor dream study

RAVELLO

Phase III study of regorefenib versus placebo as maintenance therapy in RAS wild type metastatic colorectal cancer (RAVELLO trial)

GISCAD

Intermittent versus continuous chemotherapy in advanced colorectal cancer: a randomised ‘GISCAD’ trial

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Mikhail, S., Bekaii-Saab, T. Maintenance Therapy for Colorectal Cancer: Which Regimen and Which Patients?. Drugs 75, 1833–1842 (2015). https://doi.org/10.1007/s40265-015-0467-x

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