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

Bencsikova B, Bortlicek Z, Halamkova J, Ostrizkova L, Kiss I, Melichar B, Pavlik T, Dusek L, Valik D, Vyzula R, Zdrazilova-Dubska L - BMC Gastroenterol (2015)

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

View Article: PubMed Central - PubMed

Affiliation: Department of Complex Oncology Care, Masaryk Memorial Cancer Institute, Brno, Czech Republic. bencsikova@mou.cz.

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.

No MeSH data available.


Related in: MedlinePlus

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).
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Fig1: 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).

Mentions: There was no evident bias caused by the uneven distribution of cases with KRAS mutation in two bevacizumab schedules, chemotherapeutic regimens, or first-line treatment duration. Patients with mutated KRAS tumors achieved the best treatment response and a response rate equal to the clinical outcome of the wtKRAS subgroup (Table 1). Median PFS from treatment initiation was 11.5 months (95% CI 11.0 - 12.1). Median overall survival was 29.5 months (95% CI 27.8 - 31.2). The bevacizumab regimen every 2 versus every 3 weeks resulted in comparable PFS and OS (data not shown). Median PFS was 11.5 months in wtKRAS patients vs 11.4 months in mtKRAS subgroup (Figure 1A) and median OS was in wtKRAS patients 30.7 months over 28.4 months in patients with KRAS mutation (Figure 1B).Figure 1


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

Bencsikova B, Bortlicek Z, Halamkova J, Ostrizkova L, Kiss I, Melichar B, Pavlik T, Dusek L, Valik D, Vyzula R, Zdrazilova-Dubska L - BMC Gastroenterol (2015)

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).
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Related In: Results  -  Collection

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Fig1: 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).
Mentions: There was no evident bias caused by the uneven distribution of cases with KRAS mutation in two bevacizumab schedules, chemotherapeutic regimens, or first-line treatment duration. Patients with mutated KRAS tumors achieved the best treatment response and a response rate equal to the clinical outcome of the wtKRAS subgroup (Table 1). Median PFS from treatment initiation was 11.5 months (95% CI 11.0 - 12.1). Median overall survival was 29.5 months (95% CI 27.8 - 31.2). The bevacizumab regimen every 2 versus every 3 weeks resulted in comparable PFS and OS (data not shown). Median PFS was 11.5 months in wtKRAS patients vs 11.4 months in mtKRAS subgroup (Figure 1A) and median OS was in wtKRAS patients 30.7 months over 28.4 months in patients with KRAS mutation (Figure 1B).Figure 1

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

View Article: PubMed Central - PubMed

Affiliation: Department of Complex Oncology Care, Masaryk Memorial Cancer Institute, Brno, Czech Republic. bencsikova@mou.cz.

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.

No MeSH data available.


Related in: MedlinePlus