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Evidence summaries

Second-Line Chemotherapy in Advanced and Metastatic Colorectal Cancer

Systemic therapy offers a survival benefit to people with metastatic colorectal cancer (CRC) who did not respond to first-line treatment, especially when targeted agents are combined with conventional chemotherapeutic drugs. Level of evidence: "A"

A Cochrane review [Abstract] 1 included 34 studies with a total of 13 787 subjects.

Chemotherapy (irinotecan) was more effective than best supportive care (HR for OS: 0.58, 95% CI 0.43 to 0.80; 1 RCT).

Modern chemotherapy (FOLFOX [5-fluorouracil plus leucovorin plus oxaliplatin], irinotecan) is more effective than old chemotherapy (5-fluorouracil) (HR for progress free survival PFS: 0.59, 95% CI 0.49 to 0.73; 2 RCTs) (HR for overall survival OS: 0.69, 95% CI 0.51 to 0.94; 1 RCT).

Irinotecan-based combinations were more effective than irinotecan alone (HR for PFS: 0.68, 95% CI 0.60 to 0.76; 6 RCTs).

Targeted agents improved the efficacy of conventional chemotherapy both when considered together (HR for OS: 0.84, 95% CI 0.77 to 0.91; 6 RCTs) and when bevacizumab was used alone (HR for PFS: 0.67, 95% CI 0.60 to 0.75; 4 RCTs).

With regard to secondary endpoints, tumour response rates generally paralleled the survival results; moreover, higher anticancer efficacy was generally associated with worse treatment-related toxicity, with the important exception of bevacizumab-containing regimens, where the addition of the targeted agent to chemotherapy did not result in a significant increase in the rate of serious adverse affects SAE. Oral (instead of intravenous) fluoropyrimidines significantly reduced the incidence of adverse effects (without compromising efficacy) in people treated with oxaliplatin-based regimens.

    References

    • Mocellin S, Baretta Z, Roqué I Figuls M et al. Second-line systemic therapy for metastatic colorectal cancer. Cochrane Database Syst Rev 2017;(1):CD006875. [PubMed].

Primary/Secondary Keywords