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Observational Study
. 2015 Mar 24:15:37.
doi: 10.1186/s12876-015-0266-6.

Efficacy of bevacizumab and chemotherapy in the first-line treatment of metastatic colorectal cancer: broadening KRAS-focused clinical view

Beatrix Bencsikova  1   2 , Zbynek Bortlicek  3 , Jana Halamkova  4 , Lenka Ostrizkova  5 , Igor Kiss  6   7 , Bohuslav Melichar  8 , Tomas Pavlik  9 , Ladislav Dusek  10 , Dalibor Valik  11   12 , Rostislav Vyzula  13   14   15 , Lenka Zdrazilova-Dubska  16   17   18
Affiliations
Observational Study

Efficacy of bevacizumab and chemotherapy in the first-line treatment of metastatic colorectal cancer: broadening KRAS-focused clinical view

Beatrix Bencsikova et al. BMC Gastroenterol. .

Abstract

Background: The aim of the present retrospective study was to analyze clinical outcome and risk factors associated with treatment outcomes according to KRAS status in patient with metastatic colorectal cancer (mCRC) treated with bevacizumab (bev) plus chemotherapy in the first-line setting.

Methods: We performed observational study on 1622 patients with mCRC treated with bev plus oxaliplatin- or irinotecan-based chemotherapy, and correlated treatment outcomes with KRAS mutation status. The primary endpoint was progression-free survival (PFS) and additionally overall survival (OS). Adverse events of bevacizumab and risk factors including location of metastases were evaluated.

Results: Mutation in KRAS was present in 40.6% of mCRC cases. The median PFS in patients with wild-type KRAS (wtKRAS) vs mutant KRAS was 11.5 vs 11.4 months, respectively. The median OS was 30.7 vs 28.4 months (p = 0.312). Patients with KRAS mutation had lung metastases more frequently than wtKRAS individuals (32.0% vs 23.8%; p = 0.001). We observed no difference in clinical outcome between hepatic and extrahepatic metastatic disease.

Conclusion: KRAS mutation does not interfere with clinical benefit from first-line treatment with bevacizumab plus chemotherapy in mCRC patients.

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Figures

Figure 1
Figure 1
Progression-free survival and overall survival according to KRAS mutation. A - progression-free survival; B – overall survival. Progression free survival characteristics in wtKRAS vs mtKRAS subgroups were as follows: 1-year PFS 47.3 (95% CI 43.9 - 50.7) vs 47.7% (95% CI 43.5 - 51.9), 2-year PFS 15.9 (95% CI 13.2 - 18.5) vs 17.5% (95% CI 14.0 - 21.0), 3-year PFS 8.0 (95% CI 5.8 - 10.2) vs 8.9 (95% CI 6.1 - 11.8). Overall survival characteristics in wtKRAS vs mtKRAS subgroups were as follows: 1-year OS 88.1 (95% CI 85.9 - 90.3) vs 89.2% (95% CI 86.6 - 91.8), 2-year PFS 63.0 (95% CI 59.5 - 66.5) vs 58.5% (95% CI 53.8 - 63.2), 3-year PFS 41.8 (95% CI 37.8 - 45.8) vs 38.1 (95% CI 32.8 - 43.5).
Figure 2
Figure 2
Results of multivariable Cox analysis for progression-free survival and overall survival. OX-based, FOLFOX or XELOX; IRI-based, FOLFIRI or XELIRI.
Figure 3
Figure 3
Progression-free survival and overall survival according to KRAS mutation and type of chemotherapy. A - progression-free survival; B – overall survival.
Figure 4
Figure 4
Progression-free survival and overall survival according to KRAS mutation and metastatic site in patients with metastatic disease limited to one distant organ. A, C – progression-free survival; B, D – overall survival.
See this image and copyright information in PMC

References

    1. Rak J, Mitsuhashi Y, Bayko L, Filmus J, Shirasawa S, Sasazuki T, et al. Mutant ras oncogenes upregulate VEGF/VPF expression: implications for induction and inhibition of tumor angiogenesis. Cancer Res. 1995;55:4575–80. - PubMed
    1. Takahashi Y, Kitadai Y, Bucana CD, Cleary KR, Ellis LM. Expression of vascular endothelial growth factor and its receptor, KDR, correlates with vascularity, metastasis, and proliferation of human colon cancer. Cancer Res. 1995;55:3964–8. - PubMed
    1. Hurwitz H, Fehrenbacher L, Novotny W, Cartwright T, Hainsworth J, Heim W, et al. Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer. N Engl J Med. 2004;350:2335–42. doi: 10.1056/NEJMoa032691. - DOI - PubMed
    1. Giantonio BJ, Catalano PJ, Meropol NJ, O'Dwyer PJ, Mitchell EP, Alberts SR, et al. Bevacizumab in combination with oxaliplatin, fluorouracil, and leucovorin (FOLFOX4) for previously treated metastatic colorectal cancer: results from the Eastern Cooperative Oncology Group Study E3200. J Clin Oncol. 2007;25:1539–44. doi: 10.1200/JCO.2006.09.6305. - DOI - PubMed
    1. Rak J, Yu JL, Kerbel RS, Coomber BL. What do oncogenic mutations have to do with angiogenesis/vascular dependence of tumors? Cancer Res. 2002;62:1931–4. - PubMed

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