|
Advertisement |
|
|
||
 |
|
|||||
|
|||||
|
 |
||||||
|
||||||
|
||||||
|
Journal of Clinical Oncology, Vol 26, No 12 (April 20), 2008: pp. 2060-2061 © 2008 American Society of Clinical Oncology. DOI: 10.1200/JCO.2007.15.8592
In ReplyDepartment of Medicine, Yale University, New Haven, CT
Breast Cancer Program, University of Michigan Cancer Center, Ann Arbor, MI
Department of Experimental Therapeutics, The University of Texas M.D. Anderson Cancer Center, Houston, TX We have the following responses to the concerns raised by Drs Bernards and Cardoso regarding the recently published American Society of Clinical Oncology 2007 Update of Recommendations for the Use of Tumor Markers in Breast Cancer. Bernards and Cardoso both express their opinions that the multigene assay, Oncotype DX (Genomic Health Inc, Redwood City, CA), does not meet level of evidence (LOE) II criteria and should be considered as LOE III, similar to the multigene MammaPrint (Agendia BV, Amsterdam, the Netherlands) assay. The LOE II category includes retrospective studies performed in the context of a prospective therapeutic trial in which the correlative science is not the primary end point.1 The main study describing the use of Oncotype DX was conducted with specimens collected as part of two clinical trials in which node-negative patients with estrogen receptor (ER)–positive breast cancers were prospectively treated with adjuvant tamoxifen.2 Evaluation of Oncotype DX in these studies followed prescribed statistical methods. The algorithm and cut points were established using specimens from one of these trials, and these were validated in a prespecified analysis in an entirely independent second set of patients with the same demographic and clinical characteristics. Additional retrospective LOE III studies were performed in community specimens from populations with similar characteristics.3-5 Therefore, the Committee agreed that these data were consistent with the statement from the original document that established LOE, which stated that LOE II data represent "evidence from a study in which marker data are determined in relationship to [a] prospective therapeutic trial that is performed to test [a] therapeutic hypothesis but not specifically designed to test marker utility."1 The Committee agrees with Bernards and Cardoso that available data regarding MammaPrint are, so far, LOE III. Cardoso appropriately points out that both Oncotype DX and the MammaPrint assays are being evaluated in two large prospective randomized trials (Trial Assigning Individualized Options for Treatment [TAILORx] and Microarray in Node-Negative Disease May Avoid Chemotherapy trial [MINDACT]). The Committee is supportive of the ongoing trials, which will certainly generate LOE I data. However, the design and goals of these trials are quite different. Eligibility to the TAILORx trial assumes that Oncotype DX should be used for its principal utility (identifying node-negative, ER-positive patients whose prognosis is so good that they could forego therapy), and it also assumes the data are sufficiently strong to recommend chemotherapy for those with high recurrence scores. The primary objective of TAILORx is to determine whether those patients with intermediate recurrence scores benefit sufficiently to justify adjuvant chemotherapy. This objective contrasts with that of the MINDACT trial, in which patient decisions are made based on a random assignment to use the MammaPrint assay or not. Bernards questions the choice of a 510(k)-cleared test versus a "home-brew" test. Since its inception, the Committee has made tumor marker recommendations independent of US Food and Drug Administration (FDA) status, because unlike therapeutics, diagnostics can be marketed in the United States without FDA clearance (under the "home-brew" law), and FDA deliberations for clearance do not necessarily consider clinical utility. The Committee recognizes that MammaPrint was recently cleared by the FDA. FDA clearance should be distinguished from approval. When a new device for which there is no predicate device is brought to the FDA under a premarket approval application, it may be "approved." However, the majority of submissions are 510(k) seeking clearance rather than approval. The clearance of MammaPrint includes the following statements: "The MammaPrint result is indicated for use by physicians as a prognostic marker only, along with other clinicopathological factors." "MammaPrint is not intended for diagnosis, or to predict or detect response to therapy, or to help select the optimal therapy for patients."6 Although Oncotype DX has not been cleared by the FDA, the Committee believes that existing data demonstrate that this test accurately identifies a group of patients with ER-positive, node-negative breast cancer who, assuming they take tamoxifen for 5 years, will have such a favorable prognosis that they could forego adjuvant chemotherapy. The Committee assumed that chemotherapy has the same activity in these patients with low recurrence scores that it has in other patient groups,7 because the Committee agreed that the data for the predictive role of Oncotype DX are, indeed, LOE III. Regardless, the calculated absolute benefit from chemotherapy in the group with low recurrence score will be so low that most clinicians and patients would forego this toxic therapy.8 The Committee was careful in the wording of the recommendation and followed the rules regarding peer-reviewed literature. In contrast, the Committee is unaware of any peer-reviewed literature that helps the clinician to relate MammaPrint to patients in a specific clinical situation. The Committee was unaware of the clinical laboratory improvement amendment approval or transport instructions for MammaPrint and appreciates this important update.
We agree with Cardoso that several of the topoisomerase II We disagree that the Committee was biased toward American assays. For example, urokinase plasminogen activator/plasminogen activator inhibitor-1 was entirely developed and validated in Europe. Many biomarkers developed in North America (eg, assays to detect circulating tumor cells) did not receive the Committee's recommendation. Finally, the Guideline was reviewed by members of the American Society of Clinical Oncology Board of Directors, which includes members of the European oncology community. Of note, Dr Hayes recused himself from discussions specifically concerning Oncotype DX (and as noted in the original publication, from those involving circulating tumor cells) due to conflicts of interest, but he did provide input regarding the tumor marker utility grading system and other aspects of the response. AUTHORS' DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST Although all authors completed the disclosure declaration, the following author(s) indicated a financial or other interest that is relevant to the subject matter under consideration in this article. Certain relationships marked with a "U" are those for which no compensation was received; those relationships marked with a "C" were compensated. For a detailed description of the disclosure categories, or for more information about ASCO's conflict of interest policy, please refer to the Author Disclosure Declaration and the Disclosures of Potential Conflicts of Interest section in Information for Contributors. Employment or Leadership Position: None Consultant or Advisory Role: Robert C. Bast, Vermillion (C), Fujirebio Diagnostics Inc (C), Tanox (C); Lyndsay N. Harris, LabCorp (C); Daniel F. Hayes, Abraxis (C), American Biosciences (C), AviaraDx (C), Cytogen Corp (C), Monogram Bioscience (C), Pfizer (C), Precision Therapeutics Inc (C), Prudential Financial (C), QuatRx Pharmaceuticals (C), Siemens Medical Solutions Diagnostics (C), StemCapture (C) Stock Ownership: None Honoraria: Lyndsay N. Harris, Genentech, Pfizer, Abraxis Research Funding: Robert C. Bast, Fujirebio Diagnostics Inc, Vermillion; Daniel F. Hayes, Immunicon, GlaxoSmithKline, Wyeth Ayerts-Genetics Institute, Pfizer, Novartis Expert Testimony: None Other Remuneration: None REFERENCES
1. Hayes DF, Bast RC, Desch CE, et al: Tumor marker utility grading system: A framework to evaluate clinical utility of tumor markers. J Natl Cancer Inst 88:1456-1466, 1996 2. Paik S, Shak S, Tang G, et al: A multigene assay to predict recurrence of tamoxifen-treated, node-negative breast cancer. N Engl J Med 351:2817-2826, 2004 3. Cobleigh MA, Tabesh B, Bitterman P, et al: Tumor gene expression and prognosis in breast cancer patients with 10 or more positive lymph nodes. Clin Cancer Res 11:8623-8631, 2005 4. Gianni L, Zambetti M, Clark K, et al: Gene expression profiles in paraffin-embedded core biopsy tissue predict response to chemotherapy in women with locally advanced breast cancer. J Clin Oncol 23:7265-7277, 2005 5. Habel LA, Shak S, Jacobs MK, et al: A population-based study of tumor gene expression and risk of breast cancer death among lymph node-negative patients. Breast Cancer Res 8:R25, 2006[CrossRef][Medline] 6. Draft Guidance for Industry, Clinical Laboratories, and FDA Staff In Vitro Diagnostic Multivariate Index Assays. http://www.fda.gov/cdrh/oivd/guidance/1610.pdf 7. Effects of chemotherapy and hormonal therapy for early breast cancer on recurrence and 15-year survival: An overview of the randomised trials. Lancet 365:1687-1717, 2005[CrossRef][Medline] 8. Olivotto IA, Bajdik CD, Ravdin PM, et al: Population-based validation of the prognostic model ADJUVANT! for early breast cancer. J Clin Oncol 23:2716-2725, 2005 9. Di Leo A, Gancberg D, Larsimont D, et al: HER-2 amplification and topoisomerase IIalpha gene aberrations as predictive markers in node-positive breast cancer patients randomly treated either with an anthracycline-based therapy or with cyclophosphamide, methotrexate, and 5-fluorouracil. Clin Cancer Res 8:1107-1116, 2002 10. Knoop AS, Knudsen H, Balslev E, et al: Retrospective analysis of topoisomerase II 11. O'Malley FP, Chia S, Tu D, et al: Topoisomerase II alpha protein overexpression has predictive utility in a randomized trial comparing CMF to CEF in premenopausal women with node positive breast cancer (NCIC CTG MA. 5). Presented at San Antonio Breast Cancer Symposium, San Antonio, TX, December 14-15, 2006 12. Tanner M, Isola J, Wiklund T, et al: Topoisomerase IIalpha gene amplification predicts favorable treatment response to tailored and dose-escalated anthracycline-based adjuvant chemotherapy in HER-2/neu-amplified breast cancer: Scandinavian Breast Group Trial 9401. J Clin Oncol 24:2428-2436, 2006 13. Harris LN, Dressler L, Cowan D, et al: The role of HER-2+ Topo IIa amplification in predicting benefit from CAF dose escalation: CALGB 8541. J Clin Oncol 22:836s, 2004 (suppl; abstr 9505) 14. Jacobson KK, Morrison LE, Henderson BT, et al: Gene copy mapping of the ERBB2/TOP2A region in breast cancer. Genes Chromosomes Cancer 40:19-31, 2004[CrossRef][Medline] 15. Lezon-Geyda K, Hicks JB, Tuck DP, et al: Genomic rearrangements in breast cancer: Clinical implications. Biological Therapy of Breast Cancer 8:7-11, 2007 Related Correspondence
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|
|||||||||||
|
|||||||||||
|
|
Copyright © 2008 by the American Society of Clinical Oncology, Online ISSN: 1527-7755. Print ISSN: 0732-183X
|
(Topo II) studies are LOE II, using the definitions above. In particular, the studies by DiLeo et al, 
