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David Bai, 2018 PharmD Candidate, and Michael R. Page, PharmD, RPh
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David Bai, 2018 PharmD Candidate, and Michael R. Page, PharmD, RPh
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Guidelines and Population Considerations in Colorectal Cancer

David Bai, 2018 PharmD Candidate, and Michael R. Page, PharmD, RPh
A similar study evaluated bevacizumab versus cetuximab in combination with chemotherapy as first-line treatment in Chinese patients with metastatic colon cancer, and cetuximab and bevacizumab were found to have similar efficacy. The median PFS rates were 10.6 and 8.7 months in the bevacizumab and cetuximab groups, respectively (P = .316). The median OS was 27.7 months with bevacizumab versus 28.3 months with cetuximab (P = .510). The overall response rate for cetuximab versus bevacizumab was also not significantly different (53.5% vs 43.1%; P = .108).13 In a trend, however, patients receiving cetuximab-based triplet therapy had a higher conversion rate to resectability compared with patients receiving bevacizumab-based triplet therapy (46.3% vs 28.8%; P = .058).13 In addition, in patients with peritoneal metastasis, bevacizumab proved superior to cetuximab in both PFS (9.6 vs 6.1 months; P <.001) and OS (26.3 vs 12.7 months; P = .006).13

In a third study, FIRE-3, which compared FOLFIRI in combination with either bevacizumab or cetuximab in patients with metastatic colorectal cancer, rates of PFS were found to be similar between the 2 treatment arms: 10.0 and 10.3 months for patients treated with cetuximab plus FOLFIRI and bevacizumab plus FOLFIRI, respectively (P = .55). Median OS rates were also found to be similar between the 2 treatment arms (28.7 vs 25.0 months in the cetuximab and bevacizumab arms, respectively; P = .017). However, in an analysis limited to patients with wild-type RAS, there was an advantage in OS with cetuximab compared with bevacizumab (33.1 vs 25.6 months, P = .011).14

In the fourth and final study comparing bevacizumab and cetuximab in patients with wild-type KRAS colorectal cancer, median OS was 30.0 months in patients receiving cetuximab plus chemotherapy and 29.0 months in patients receiving bevacizumab plus chemotherapy (P = .08).15 Rates of median PFS times were also similar between the cetuximab and bevacizumab groups, with durations of 10.5 months and 10.6 months, respectively (P = .45).15 Finally, the respective response rates for cetuximab and bevacizumab were 59.6% and 55.2% (P = .13).15


Targeted therapy includes a novel group of treatments that may help improve outcomes for patients with metastatic colon cancer, as monotherapy, and in some cases, when used in combination with chemotherapy. Targeted therapies are different from chemotherapy in that they target specific receptors that may promote cancer growth and survival. Because these drugs are reserved for patients with advanced cancer, few head-to-head trials have been performed. However, it is important to recognize the available evidence and possible differences among treatments both across and within treatment classes.

1. National Cancer Institute (NCI). Targeted cancer therapies. NCI website. Reviewed June 8, 2017. Accessed July 2017.
2. National Comprehensive Cancer Network (NCCN). NCCN guidelines for patients. Colon cancer. Version 1.2017. NCCN website. Updated June 6, 2017. Accessed June 2017.
3. National Comprehensive Cancer Network (NCCN). Clinical practices in oncology (NCCN guidelines). Colon cancer. Version 2.2017 NCCN website. Published March 13, 2017.  Accessed July 2017.
4. Hurwitz H, Fehrenbacher L, Novotny W, et al. Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer. N Engl J Med. 2004;350(23):2335-2342.
5. Cunningham D, Humblet Y, Siena S, et al. Cetuximab monotherapy and cetuximab plus irinotecan in irinotecan-refractory metastatic colorectal cancer. N Engl J Med. 2004;351(4):337-345.
6. Van Cutsem E, Peeters M, Siena S, et al. Open-label phase III trial of panitumumab plus best supportive care compared with best supportive care alone in patients with chemotherapy-refractory metastatic colorectal cancer. J Clin Oncol. 2007;25(13):1658-1664.
7. Tabernero J, Yoshino T, Cohn AL. Ramucirumab versus placebo in combination with second-line FOLFIRI in patients with metastatic colorectal carcinoma that progressed during or after first-line therapy with bevacizumab, oxaliplatin, and a fluoropyrimidine (RAISE): a randomised, double-blind, multicentre, phase 3 study [Correction to Lancet Oncol 2015;16:499-508]. Lancet Oncol. 2015;16(6):e262. doi: 10.1016/S1470-2045(15)70273-1.
8. Van Cutsem E, Joulain F, Hoff PM, et al. Aflibercept plus FOLFIRI vs. placebo plus FOLFIRI in second-line metastatic colorectal cancer: a post hoc analysis of survival from the phase III VELOUR study subsequent to exclusion of patients who had recurrence during or within 6 months of completing adjuvant oxaliplatin-based therapy. Target Oncol. 2016;11(3):383-400. doi: 10.1007/s11523-015-0402-9.
9. Grothey A, Van Cutsem E, Sobrero A, et al; CORRECT Study Group. Regorafenib monotherapy for previously treated metastatic colorectal cancer (CORRECT): an international, multicentre, randomised, placebo-controlled, phase 3 trial. Lancet. 2013;381(9863):303-312. doi: 10.1016/S0140-6736(12)61900-X.
10. Price T, Kim TW, Li J, et al. Final results and outcomes by prior bevacizumab exposure, skin toxicity, and hypomagnesaemia from ASPECCT: randomized phase 3 non-inferiority study of panitumumab versus cetuximab in chemorefractory wild-type KRAS exon 2 metastatic colorectal cancer. Eur J Cancer. 2016;68:51-59. doi: 10.1016/j.ejca.2016.08.010.
11. Graham CN, Maglinte GA, Schwartzberg LS, et al. Economic analysis of panitumumab compared with cetuximab in patients with wild-type KRAS metastatic colorectal cancer that progressed after standard chemotherapy. Clin Ther. 2016;38(6):1376-1391. doi: 10.1016/j.clinthera.2016.03.023.
12. Stintzing S, Fischer von Weikersthal L, Decker T, et al. FOLFIRI plus cetuximab versus FOLFIRI plus bevacizumab as first-line treatment for patients with metastatic colorectal cancer-subgroup analysis of patients with KRAS: mutated tumours in the randomised German AIO study KRK-0306. Ann Oncol. 2012;23(7):1693-1699. doi: 10.1093/annonc/mdr571.
13. Bai L, Wang F, Li ZZ, et al. Chemotherapy plus bevacizumab versus chemotherapy plus cetuximab as first-line treatment for patients with metastatic colorectal cancer: results of a registry-based cohort analysis. Medicine (Baltimore). 2016;95(51):e4531. doi: 10.1097/MD.0000000000004531.
14. Heinemann V, von Weikersthal LF, Decker T, et al. FOLFIRI plus cetuximab versus FOLFIRI plus bevacizumab as first-line treatment for patients with metastatic colorectal cancer (FIRE-3): a randomised, open-label, phase 3 trial. Lancet Oncol. 2014;15(10):1065-1075. doi: 10.1016/S1470-2045(14)70330-4.
15. Venook AP, Niedzwiecki D, Lenz HJ, et al. Effect of first-line chemotherapy combined with cetuximab or bevacizumab on overall survival in patients with KRAS wild-type advanced or metastatic colorectal cancer: a randomized clinical trial. JAMA. 2017;317(23):2392-2401. doi: 10.1001/jama.2017.7105.
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