Efficacy of first-line oxaliplatin-based chemotherapy regimens depending on the KRAS mutation status

Objective: to determine the efficacy of 2 oxaliplatin-based chemotherapy regimens (FOLFOX and XELOX) for metastatic colorectal cancer (CRC) depending on the KRAS mutation status and primary tumor location. Materials and methods. We performed retrospective analysis of the data on patients with metastatic CRC taken from a prospective database. We included patients with known KRAS mutation status that received either FOLFOX or XELOX without targeted drugs. Progression-free survival (PFS) was used as a main criterion in estimating treatment efficacy. Results. The inclusion criteria were met by 157 patients. The FOLFOX regimen was more effective in patients with wild-type KRAS CRC: median PFS was 10 months versus 8 months in the XELOX group (hazard ratio (HR) = 0.7; 95 % confidence interval (CI) 0.4–1.2; р = 0.1). However, we observed no significant differences in median life expectancy between these groups: it was 37 and 38 months respectively (HR = 1.1; 95 % CI 0.6–2.1; p = 0.6). Similar trends were observed in patients bearing KRAS mutations: median PFS in the FOLFOX group was 9 months vs 5 months in the XELOX group (HR = 0.6; 95 % CI 0.3–1.2; р = 0.1; p value by Breslow – Day test = 0.04). No differences in median life expectancy between these groups were observed: 33 and 23 months respectively (HR = 0.8; 95 % CI 0.4–1.6; p = 0.5). Conclusion. We failed to find an association between the KRAS mutation status and response to a particular chemotherapy regimen. We found that patients with metastatic CRC receiving the FOLFOX regimen were more likely to achieve objective responses and demonstrated higher median PFS than patients on the XELOX regimen.

1. Chau I., Cunningham D. Treatment in advanced colorectal cancer: what, when and how? Br J Cancer 2009;100(11):1704–19. PMID: 19436303. DOI: 10.1038/sj.bjc.6605061.

2. Khattak M. A., Martin H., Davidson A., Phillips M. Role of first-line anti- epidermal growth factor receptor therapy compared with anti-vascular endothelial growth factor therapy in advanced colorectal cancer: a meta-analysis of randomized clinical trials. Clin Colorectal Cancer 2015;14(2):81–90. PMID: 25666296. DOI: 10.1016/j.clcc.2014.12.011.

3. Venook A. P., Niedzwiecki D., Innocenti F. et al. Impact of primary (1°) tumor location on overall survival (OS) and progression-free survival (PFS) in patients (pts) with metastatic colorectal cancer (mCRC): analysis of CALGB/SWOG 80405 (Alliance). J Clin Oncol 2016;34(suppl 15):3504. DOI: 10.1200/ JCO.2016.34.15_suppl. 3504.

4. Tveit K. M., Guren T., Glimelius B. et al. Phase III trial of cetuximab with continuous or intermittent fluorouracil, leucovorin, and oxaliplatin (Nordic FLOX) versus FLOX alone in first-line treatment of metastatic colorectal cancer: the NORDIC-VII study. J Clin Oncol 2012;30(15): 1755–62. PMID: 22473155. DOI: 10.1200/JCO.2011.38.0915.

5. Maughan T. S., Adams R. A., Smith C. G. et al. Addition of cetuximab to oxaliplatin-based first-line combination chemotherapy for treatment of advanced colorectal cancer: results of the randomised phase 3 MRC COIN trial. Lancet 2011;377(9783): 2103–14. PMID: 21641636. DOI: 10.1016/S0140-6736(11)60613-2.

6. Buchler T., Pavlik T., Melichar B. et al. Bevacizumab with 5-fluorouracil, leucovorin, and oxaliplatin versus bevacizumab with capecitabine and oxaliplatin for metastatic colorectal carcinoma: results of a large registry-based cohort analysis. BMC Cancer 2014;(14):323. PMID: 24884897. DOI: 10.1186/1471-2407-14-323.

7. Hochster H.S., Hart L.L., Ramana-than R.K., et al. Safety and efficacy of oxaliplatin and fluoropyrimidine regimens with or without bevacizumab as first-line treatment of metastatic colorectal cancer: results of the TREE Study. J Clin Oncol. 2008 Jul 20;26(21):3523–9.

8. Saltz L. B., Clarke S., Diaz-Rubio E. et al. Bevacizumab in combination with oxalipla tin-based chemotherapy as first-line therapy in metastatic colorectal cancer: a randomized phase III study. J Clin Oncol 2008;26(12):2013–9. PMID: 18421054. DOI: 10.1200/JCO.2007.14.9930.

9. Saltz L. B., Clarke S., Diaz-Rubio E. et al. Bevacizumab (Bev) in combination with XELOX or FOLFOX4: efficacy results from XELOX-1/NO16966, a randomized phase III trial in the first-line treatment of metastatic colorectal cancer (MCRC). ASCO 2007 Gastrointestinal Cancers Symposium. Abstr. 238.