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Background Metastatic colorectal cancer (mCRC) is mainly a disease of elderly, however, geriatric population is underrepresented in clinical trials. Patient registries represent a tool to assess and follow treatment outcomes in this patient population. The aim of the study was with the help of the patients’ register to determine the safety and efficacy of bevacizumab plus chemotherapy in elderly patients who had previously untreated metastatic colorectal cancer. Patients and methods The registry of patients with mCRC was designed to prospectively evaluate the safety and efficacy of bevacizumab-containing chemotherapy as well as selection of patients in routine clinical practice. Patient baseline clinical characteristics, pre-specified bevacizumab-related adverse events, and efficacy data were collected, evaluated and compared according to the age categories. Results Between January 2008 and December 2010, 210 patients with mCRC (median age 63, male 61.4%) started bevacizumab-containing therapy in the 1st line setting. Majority of the 210 patients received irinotecan-based chemotherapy (68%) as 1st line treatment and 105 patients (50%) received bevacizumab maintenance therapy. Elderly (≥ 70 years) patients presented 22.9% of all patients and they had worse performance status (PS 1/2, 62.4%) than patients in < 70 years group (PS 1/2, 35.8%). Difference in disease control rate was mainly due to inability to assess response in elderly group (64.6% in elderly and 77.8% in < 70 years group, p = 0.066). The median progression free survival was 10.2 (95% CI, 6.7–16.2) and 11.3 (95% CI, 10.2–12.6) months in elderly and < 70 years group, respectively (p = 0.58). The median overall survival was 18.5 (95% CI, 12.4–28.9) and 27.4 (95% CI, 22.7–31.9) months for elderly and < 70 years group, respectively (p = 0.03). Three-year survival rate was 26% and 37.6% in elderly vs. < 70 years group (p = 0.03). Overall rates of bevacizumab-related adverse events were similar in both groups: proteinuria 21/22 %, hypertension 25/19 %, haemorrhage 2/4 % and thromboembolic events 10/6 %, for elderly and < 70 years group, respectively. Conclusions In routine clinical practice, the combination of bevacizumab and chemotherapy is effective and well-tolerated regimen in elderly patients with metastatic colorectal cancer.

Background. KRAS mutation status in codons 12 and 13 is recognized as a predictive factor for resistance to anti-EGFR monoclonal antibodies. Despite having a wild type KRAS (wt-KRAS), not all patients with wt-KRAS respond to anti-EGFR antibody treatment. Additional mechanisms of resistance may activate mutations of the other main EGFR effectors pathway. Consequently, other molecular markers in colorectal cancer are needed to be evaluated to predict the response to therapy. Patients and methods. In this retrospective study, objective responses (OR), time to progression (TTP), overall survival (OS) were analyzed in 176 metastatic colorectal cancer (mCRC) patients treated with first-line chemotherapy in combination with monoclonal antibodies in respect of KRAS status in codons 12 and 13 and BRAF mutational status. Results. The KRAS mutations were found in 63 patients (35.8 %), the KRAS mutation in codon 12 in 53 patients (30.1%) and the KRAS mutation in codon 13 in 10 patients (5.7%). The BRAF V600E mutation was detected in 13 of 176 patients (7.4%). In the subgroup of mCRC patients having wt-KRAS and wild type BRAF (wt-BRAF), the objective response rates were higher (OR 54.0%, CR 14.7%, PR 39.3%) than in the patients with wt-KRAS and mt-BRAF (OR 38.5%,CR 15.4%, PR 23.1%), the difference was not statistically significant (p= 0.378). Median OS in patients with wt-KRAS wt-BRAF, and in patients with wt-KRAS mt-BRAF, was 107.4 months and 45 months, respectively. The difference was statistically significant (p= 0.042). TTP in patients with wt-KRAS wt-BRAF, and in patients with wt-KRAS mt-BRAF, was 16 months and 12 months, respectively. The difference was not statistically significant (p= 0.558). Conclusions. Patients with BRAF V600E mutation have statistically significantly worse prognosis than the patients with wt-BRAF and progress earlier during treatment. The definitive role of the BRAF V600E mutation as a prognostic and predictive factor for the response to anti-EGFR monoclonal antibodies needs to be analyzed in large prospective clinical studies.

e14642 Background: This is the registry of patients (pts) with metastatic colorectal cancer (mCRC) designed to prospectively evaluate the safety and efficacy of bevacizumab-containing chemotherapy ...

Introduction KRAS mutation status in codons 12 and 13 is recognized as a predictive factor for resistance to anti- EGFR monoclonal antibodies. Recent retrospective studies suggested that patients (pts) with different KRAS mutations (KRAS mts) respond different to specific systemic therapy and also pts with KRAS mt in codon 13 might respond to anti- EGFR monoclonal antibodies but with lower response rates than pts with KRAS wild-type (KRAS wt) tumors. Methods Objective response (OR), time to progression (TTP), overall survival (OS) and BRAF status in metastatic colorectal cancer (mCRC) pts treated with first- line therapy according to KRAS status, were retrospectively analyzed. Results In total 176 mCRC pts who received first- line therapy between May 2009 and October 2010 were included in retrospective analysis. The median age was 62 years (27- 86), M/F 61/39 %. The most common received therapies were XELIRI/bevacizumab and XELOX/cetuximab in 29.5 % and in 22.1 % of pts respectively. KRAS mts were found in 63 pts (35.8 %), mt KRAS in codon 12 in 53 pts (84%) and mt KRAS in codon 13 in 10 pts (16%). BRAF V600E mt was detected in 13 of 176 pts (7.4%). OR in wt KRAS/wt BRAF pts was 54% (CR 14.7 %, PR 39.3 %) and in wt KRAS/mt BRAF pts was 38.5% (CR 15.4 %, PR 23.1 %), difference (diff) was not statistically significant (p= 0.378). Median OS of wt KRAS/wt BRAF pts and wt KRAS/mt BRAF pts was 107.4 months (mo) (95% CI: 82- 132.9 mo) and 45 mo (95% CI: 28.4- 61.5 mo) respectively, diff was statistically significant (p= 0.042). TTP in wt KRAS/ wt BRAF pts and wt KRAS/mt BRAF pts was 16 mo (95% CI: 10.7- 21.2 mo) and 12 mo (95% CI: 4.0 -15.0 mo) respectively, diff was not statistically significant (p= 0.558). OR in codon 12 mt pts was 47% (CR 20.7%, PR 26.3%) and in codon 13 mt pts was 33% (CR 11%, PR 22%),dif was not statistically significant (p= 0.08). TTP in mt codon 12 pts and mt codon 13 pts was 13.5 mo (95% CI: 9.0- 18.0 months) and 9.3 mo (95% CI: 5.1- 13.5 mo) respectively, diff was not statistically significant (p= 0.106). Conclusion Mt BRAF pts have statistically significantly worse prognosis than wt BRAF pts, with lower response rates and progress earlier during systemic treatment. Codon 13 mt KRAS pts have lower response rate and progress earlier than KRAS codon 12 mt pts. Definitive role of mt BRAF and different KRAS mts are needed to be defined to select pts, who will benefit from specific combination of systemic therapy.