Treatment Patterns and Outcomes in Patients with KRAS Wild-Type Metastatic Colorectal Cancer Treated in First Line with Bevacizumab- or Cetuximab-Containing Regimens
- 240 Downloads
Patients with Kirsten rat sarcoma viral oncogene wild-type (KRAS WT) metastatic colorectal cancer (mCRC) treated in first line with bevacizumab (B) or cetuximab (C) plus standard chemo backbones had comparable outcomes in phase III Cancer and Leukemia Group B (CALGB) 80405. We examined comparative effectiveness of B and C regimens in real-world community settings.
This retrospective study examined progression-free survival (PFS) and OS in a US community sample of KRAS WT mCRC patients treated with first-line B (n = 254) or C (n = 146) regimens. Medical records from the Vector Oncology Data Warehouse were used. Disease progression was determined from patient charts. OS was measured from the start of first-line treatment until death.
There were no significant difference in either PFS or OS respectively between B-treated compared to C-treated patients (HR = 1.324, 95% CI 0.901, 1.947; HR = 1.080, 95% CI 0.721, 1.617). More B patients received oxaliplatin backbones (74.8 vs. 36.3%), and more C patients received irinotecan backbones (51.4 vs. 20.1%), ps < 0.001. Multivariate survival analyses showed a significant difference indicating a greater risk for death among C-treated patients with right-sided tumors vs. left-sided tumors (HR = 2.263, 95% CI 1.394, 3.673, p = 0.0009), but not for B-treated patients (HR = 1.209, 95% CI 0.825, 1.771, p = 0.3297).
Consistent with CALGB 80405, median PFS and OS for these community oncology KRAS WT mCRC patients treated with first-line B or C regimens did not differ significantly.
KeywordsComparative effectiveness Community oncology Progression-free survival Overall survival Tumor location
This work was funded by Genentech, Inc.
Compliance with Ethical Standards
Conflict of Interest
AH reported no conflict of interest. SO and NS are employed by and own stock in Genentech, Inc. SSH and MW are consultants for Genentech. Genentech sponsored this study and provided financial support for the conduct of the research and for preparation of the article. Genentech collaborated on the design of the study, interpretation of the analyses, and in the decision to submit the article for publication, but did not have a direct role in data collection, data analysis, or writing of the report.
Research Involving Human Participants
This research was reviewed and approved by IntegReview Institutional Review Board, in Austin, TX. All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.
For this type of study, formal consent is not required.
- 4.Falcone A, Ricci S, Brunetti I, Pfanner E, Allegrini G, Barbara C, et al. Gruppo Oncologico Nord O. Phase III trial of infusional fluorouracil, leucovorin, oxaliplatin, and irinotecan (FOLFOXIRI) compared with infusional fluorouracil, leucovorin, and irinotecan (FOLFIRI) as first-line treatment for metastatic colorectal cancer: the Gruppo Oncologico Nord Ovest. J Clin Oncol. 2007;25(13):1670–6. https://doi.org/10.1200/JCO.2006.09.0928.CrossRefGoogle Scholar
- 5.Goldberg RM, Sargent DJ, Morton RF, Fuchs CS, Ramanathan RK, Williamson SK, et al. A randomized controlled trial of fluorouracil plus leucovorin, irinotecan, and oxaliplatin combinations in patients with previously untreated metastatic colorectal cancer. J Clin Oncol. 2004;22(1):23–30. https://doi.org/10.1200/JCO.2004.09.046.CrossRefPubMedGoogle Scholar
- 6.Starling N, Tilden D, White J, Cunningham D. Cost-effectiveness analysis of cetuximab/irinotecan vs active/best supportive care for the treatment of metastatic colorectal cancer patients who have failed previous chemotherapy treatment. Br J Cancer. 2007;96(2):206–12. https://doi.org/10.1038/sj.bjc.6603561.CrossRefPubMedPubMedCentralGoogle Scholar
- 9.Tabernero J, van Cutsem E, Lakomy R, Prausova J, Ruff P, van Hazel G, et al. Results from VELOUR, a phase III study of aflibercept versus placebo in combination with FOLFIRI for the treatment of patients with previously treated metastatic colorectal cancer (MCRC). Eur J Cancer. 2011;47(suppl 2):5. Abstract 6LBACrossRefGoogle Scholar
- 10.Grothey A, Van Cutsem E, Sobrero A, Siena S, Falcone A, Ychou M, et al. Regorafenib monotherapy for previously treated metastatic colorectal cancer (CORRECT): an international, multicentre, randomised, placebo-controlled, phase 3 trial. Lancet. 2013;381(9863):303–12. https://doi.org/10.1016/S0140-6736(12)61900-X.CrossRefGoogle Scholar
- 15.Venook AP, Niedzwiecki D, Lenz H-J, Innocenti F, Mahoney MR, O'Neil BH, et al. CALGB/SWOG 80405: phase III trial of irinotecan/5-FU/leucovorin (FOLFIRI) or oxaliplatin/5-FU/leucovorin (mFOLFOX6) with bevacizumab (BV) or cetuximab (CET) for patients (pts) with KRAS wild-type (wt) untreated metastatic adenocarcinoma of the colon or rectum (MCRC). J Clin Oncol. 2014;32:5s.Google Scholar
- 16.Schrag D, Weng S, Brooks G, Meyerhardt J, Venook AP, The relationship between primary tumor sidedness and prognosis in colorectal cancer. Chicago: Publisher; 2016.Google Scholar
- 17.Heinemann V, Modest DP, von Weikersthal LF, Decker T, Kiani A, Vehling-Kaiser U, Al-Batran S, Heintges T, et al., Gender and tumor location as predictors of efficacy in 1st-line treatment with FOLFIRI plus cetuximab or bevacizumab—results from the AIO KRK-0306 (FIRE3) trial. Chicago: Publisher; 2014.Google Scholar
- 18.von Einem JC, Heinemann V, von Weikersthal LF, Vehling-Kaiser U, Stauch M, Hass HG, et al. Left-sided primary tumors are associated with favorable prognosis in patients with KRAS codon 12/13 wild-type metastatic colorectal cancer treated with cetuximab plus chemotherapy: an analysis of the AIO KRK-0104 trial. J Cancer Res Clin Oncol. 2014;140(9):1607–14. https://doi.org/10.1007/s00432-014-1678-3.CrossRefGoogle Scholar
- 19.Venook AP, Niedzwiecki D, Innocenti F, Fruth B, Greene C, O’Neil B, Shaw J, et al. Impact of primary tumor location on overall survival and progression free survival in patients with metastatic colorectal cancer: analysis of CALGB/SWOG 80405 (Alliance). Chicago: Publisher; 2016.Google Scholar
- 20.Chan DL, Pavlakis N, Shapiro J, Price TJ, Karapetis CS, Tebbutt NC, et al. Does the chemotherapy backbone impact on the efficacy of targeted agents in metastatic colorectal cancer? A systematic review and meta-analysis of the literature. PLoS One. 2015;10(8):e0135599. https://doi.org/10.1371/journal.pone.0135599.CrossRefPubMedPubMedCentralGoogle Scholar
- 21.Oliner KS, Douillard J-Y, Siena S, Tabernero J, Burkes RL, Barugel ME, et al. Analysis of KRAS/NRAS and BRAF mutations in the phase III PRIME study of panitumumab (pmab) plus FOLFOX versus FOLFOX as first-line treatment (tx) for metastatic colorectal cancer (mCRC). J Clin Oncol, 2013 ASCO Annual Meeting Abstracts. 2013;31:3511.Google Scholar
- 22.Stintzing S, Jung A, Rossius L, et al. Analysis of KRAS/NRAS and BRAF mutations in FIRE-3: a randomized phase III study of FOLFIRI plus cetuximab or bevacizumab as first-line treatment for wild-type (WT) KRAS (exon 2) metastatic colorectal cancer (mCRC) patients. 2013 September 27–1 October, Amsterdam: Publisher; 2013.Google Scholar
- 24.American Cancer Society. Colorectal Cancer Facts and Figures 2014-2016 Atlanta: American Cancer Society; 2014 [April 12, 2016]. Available from: http://www.cancer.org/acs/groups/content/documents/document/acspc-042280.pdf.