Display options
Cite
KRAS Testing for Anti-EGFR Therapy in Advanced Colorectal Cancer: An Evidence-Based and Economic Analysis. Ont Health Technol Assess Ser. 2010;10(25):1-49
(2010). KRAS Testing for Anti-EGFR Therapy in Advanced Colorectal Cancer: An Evidence-Based and Economic Analysis. Ontario health technology assessment series, 10(25), 1-49.
"KRAS Testing for Anti-EGFR Therapy in Advanced Colorectal Cancer: An Evidence-Based and Economic Analysis." Ontario health technology assessment series vol. 10,25 (2010): 1-49.
KRAS Testing for Anti-EGFR Therapy in Advanced Colorectal Cancer: An Evidence-Based and Economic Analysis. Ont Health Technol Assess Ser. 2010;10(25):1-49. Epub 2010 Dec 01. PMID: 23074403; PMCID: PMC3377508.
Copy Download .nbib Format: NLM
Share it on

Ont Health Technol Assess Ser. 2010;10(25):1-49. Epub 2010 Dec 01.

KRAS Testing for Anti-EGFR Therapy in Advanced Colorectal Cancer: An Evidence-Based and Economic Analysis.

Ontario health technology assessment series

[No authors listed]

PMID: 23074403 PMCID: PMC3377508

Abstract

LITERATURE SEARCH: The Medical Advisory Secretariat followed its standard procedures and on May 18, 2010, searched the following electronic databases: Ovid MEDLINE, EMBASE, Ovid MEDLINE In-Process & Other Non-Indexed Citations, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews and The International Network of Agencies for Health Technology Assessment database. The subject headings and keywords searched included colorectal cancer, cetuximab, panitumumab, and KRAS testing. The search was further restricted to English-language articles published between January 1, 2009 and May 18, 2010 resulting in 1335 articles for review. Excluded were case reports, comments, editorials, nonsystematic reviews, and letters. Studies published from January 1, 2005 to December 31, 2008 were identified in a health technology assessment conducted by the Agency for Healthcare Research and Quality (AHRQ), published in 2010. In total, 14 observational studies were identified for inclusion in this EBA: 4 for cetuximab monotherapy, 7 for the cetuximab-irinotecan combination therapy, and 3 to be included in the review for panitumumab monotherapy

INCLUSION CRITERIA: English-language articles, and English or French-language HTAs published from January 2005 to May 2010, inclusive.Randomized controlled trials (RCTs) or observational studies, including single arm treatment studies that include KRAS testing.Studies with data on main outcomes of interest, overall and progression-free survival.Studies of third line treatment with cetuximab or panitumumab in patients with advanced colorectal cancer refractory to chemotherapy.For the cetuximab-irinotecan evaluation, studies in which at least 70% of patients in the study received this combination therapy.

EXCLUSION CRITERIA: Studies whose entire sample was included in subsequent publications which have been included in this EBA.Studies in pediatric populations.Case reports, comments, editorials, or letters.

OUTCOMES OF INTEREST: Overall survival (OS), medianProgression-free-survival (PFS), median.Response rates.Adverse event rates.Quality of life (QOL). SUMMARY OF FINDINGS OF SYSTEMATIC REVIEW: CETUXIMAB OR PANITUMUMAB MONOTHERAPY: Based on moderate GRADE observational evidence, there is improvement in PFS and OS favouring patients without the KRAS mutation (KRAS wildtype, or KRAS WT) compared to those with the mutation. CETUXIMAB-IRINOTECAN COMBINATION THERAPY: There is low GRADE evidence that testing for KRAS may optimize survival benefits in patients without the KRAS mutation (KRAS wildtype, or KRAS WT) compared to those with the mutation. However, cetuximab-irinotecan combination treatments based on KRAS status discount any effect of cetuximab in possibly reversing resistance to irinotecan in patients with the mutation, as observed effects were lower than for patients without the mutation. Clinical experts have raised concerns about the biological plausibility of this observation and this conclusion would, therefore, be regarded as hypothesis generating.

ECONOMIC ANALYSIS: Cost-effectiveness and budget impact analyses were conducted incorporating estimates of effectiveness from this systematic review. Evaluation of relative cost-effectiveness, based on a decision-analytic cost-utility analysis, assessed testing for KRAS genetic mutations versus no testing in the context of treatment with cetuximab monotherapy, panitumumab monotherapy, cetuximab in combination with irinotecan, and best supportive care. Of importance to note is that the cost-effectiveness analysis focused on the impact of testing for KRAS mutations compared to no testing in the context of different treatment options, and does not assess the cost-effectiveness of the drug treatments alone.

CONCLUSIONS: KRAS status is predictive of outcomes in cetuximab and panitumumab monotherapy, and in cetuximab-irinotecan combination therapy. While KRAS testing is cost-effective for all strategies considered, it is not equally cost-effective for all treatment options.

References

  1. J Natl Cancer Inst. 2009 Sep 2;101(17):1182-92 - PubMed
  2. N Engl J Med. 2008 Oct 23;359(17):1757-65 - PubMed
  3. Clin Cancer Res. 2009 May 1;15(9):3184-8 - PubMed
  4. Curr Oncol. 2010 Jul;17 Suppl 1:S31-40 - PubMed
  5. J Clin Oncol. 2007 May 1;25(13):1658-64 - PubMed
  6. J Clin Oncol. 2009 Apr 20;27(12):2091-6 - PubMed
  7. J Clin Oncol. 2007 Aug 1;25(22):3230-7 - PubMed
  8. Jpn J Clin Oncol. 2009 May;39(5):321-6 - PubMed
  9. Clin Colorectal Cancer. 2008 May;7(3):184-90 - PubMed
  10. BMJ. 2004 Jun 19;328(7454):1490 - PubMed
  11. Br J Cancer. 2008 Jul 8;99(1):83-9 - PubMed
  12. J Clin Oncol. 2008 Sep 1;26(25):4217-9 - PubMed
  13. Clin Cancer Res. 2008 Dec 1;14(23):7884-95 - PubMed
  14. J Clin Oncol. 2009 Mar 1;27(7):1122-9 - PubMed
  15. J Clin Oncol. 2008 Apr 1;26(10):1626-34 - PubMed
  16. Int J Technol Assess Health Care. 1994 Fall;10(4):714-5 - PubMed
  17. Ann Oncol. 2008 Jan;19(1):92-8 - PubMed
  18. N Engl J Med. 2007 Nov 15;357(20):2040-8 - PubMed
  19. BMC Cancer. 2008 Jun 10;8:169 - PubMed
  20. J Clin Oncol. 2009 Jun 1;27(16):2622-9 - PubMed
  21. BMC Med Res Methodol. 2005 Apr 20;5:13 - PubMed
  22. Br J Cancer. 2009 Apr 21;100(8):1330-5 - PubMed
  23. Ann Oncol. 2009 May;20(5):879-84 - PubMed
  24. J Clin Oncol. 2008 Jan 20;26(3):374-9 - PubMed
  25. N Engl J Med. 2004 Jul 22;351(4):337-45 - PubMed
  26. Br J Cancer. 2009 Aug 18;101(4):715-21 - PubMed
  27. Br J Cancer. 2007 Dec 3;97(11):1469-74 - PubMed

Publication Types