engleski

Does metastatic colorectal cancer in elderly patients have specific features: the final results of prospective phase Iistudy of bevacizumab in combination with capecitabin

Introduction: In our prospective phase II study, published in 2011, we demonstrated that bevacizumab in combination with capecitabine as first-line treatment is effective in elderly patients with metastatic colorectal cancer (mCRC) which was later confirmed by a phase III trial. Here, we present results of the final analysis of our study, considering the molecular biology, primary tumor location, post progression therapy and their correlation with patients’ outcomes. Methods: We prospectively and retrospectively analyzed the outcome of 40 patients, aged 70, initially treated with bevacizumab and capecitabine in the first line setting, regarding objective response rate (ORR), progression-free survival (PFS) and overall survival (OS) in correlation with RAS, BRAF, microsatellite status, primary tumor location and post-progression therapy. The tumor tissue samples were analyzed using immunohistochemical staining for microsatellite status and mutational tests for RAS and BRAF status. For the subgroup analysis, we used data collected from patient charts. Results: After a median follow-up time of 20.5 months, median PFS and OS were 9.8 and 20.5 months, respectively. The ORR was 65%. Twelve patients had a mutation in RAS gene (11 in KRAS and 1 inNRAS). There was no significant difference between RAS status and studied outcomes (RAS mt vs RAS wt: ORR 54 vs 71%, p¼0.46 ; PFS 8.7 vs 13 months, p¼0.95 and OS 19.1 vs 23 months, p¼0.95). Four patients had mutated BRAF (V600E/E2/D in three and K601E in one of them) and two of thesemutations (both V600E/E2/D) coexisted withMSI. BRAF mutation was more prevalent in right-sided as opposed to left-sided tumors (43% vs 3.7% ; p¼0.02). Neither patient had mutation both in RAS and BRAF gene. There were 2 patients withMSI (MLH1- orPMS2-) and both had the coexistentmutation in the BRAF gene and the right-sided primary tumor which was associated with a poor outcome. The primary tumor was left-sided in 31 and right-sided in 9 patients. The patients with right-sided tumors had apparently, but not significantly lower PFS (8.6 vs 13 months, p¼0.14) and significantly lower OS (13 vs 23.1months, p¼0.046).Compared to the patients with left-sided primary tumors, BRAF mutation was more prevalent in patients with right-sided primary tumors (3/7¼43%vs. 1/27¼3.7% ; p¼0.02). Patients with 2 or more post progression therapy lines had a significantly betterORR (14/28¼50%vs.12/12¼100%, p¼0.003), PFS (medians: 8.5 vs. 17.2 months, p¼0.0006) and OS (medians:13 vs.42 months, p¼0.0002). Conclusion: Elderly mCRC patients could differ from the younger ones considering the tolerability, response to therapy and survival outcomes. Their tumors could potentially have different biological and molecular patterns. Following progression, introducing new therapy lines in older mCRC patients is both feasible and associated with significantly better outcomes. Therefore, in the decision how to treat elderly mCRC patients we should be led by their biological rather than their chronological age and by tumor characteristics. The right-sided primary tumors were related with poorer outcomes compared with the left-sided primary tumors which is consistent with recent findings on the importance of primary tumor location.

Colorectal cancer, elderly

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