title: Integrating comparative effectiveness design elements and endpoints into a phase III, randomized clinical trial (SWOG S1007) evaluating oncotypeDX-guided management for women with breast cancer involving lymph nodes.
abstract: Women with breast cancer involving the lymph nodes are typically treated with cytotoxic chemotherapy. Retrospective evaluations of prior studies suggest that the 21-gene test (OncotypeDX®), may allow identification of those who can safely avoid chemotherapy. To better understand the performance of the 21-gene test, the RxPONDER (Rx for Positive Node, Endocrine Responsive breast cancer) study was designed, a multicenter Phase III trial randomizing women with hormone receptor-positive and HER2-negative breast cancer involving 1-3 lymph nodes and a 21-gene assay recurrence score (RS) of 25 or less to endocrine therapy alone versus chemotherapy followed by endocrine therapy. As one of the first large-scale comparative-effectiveness studies in oncology, RxPONDER utilized an external stakeholder group to help inform the design of the trial. Stakeholders met with representatives of SWOG over several months through a structured discussion process. The stakeholder engagement process resulted in several changes being made to the trial design. In addition, stakeholder representatives from the health insurance industry provided guidance regarding a mechanism whereby the costs of OncotypeDX® would be paid by the majority of health insurers as part of the trial. The process may serve as a template for future studies evaluating the comparative effectiveness of genomic tests in oncology, particularly those that are conducted within cooperative clinical trials groups.
authors.affiliation: Fred Hutchinson Cancer Research Center, Seattle, WA 98109–1024, United States. sramsey@fhcrc.org
authors.forename: Scott D
authors.initials: SD
authors.lastname: Ramsey
authors.forename: William E
authors.initials: WE
authors.lastname: Barlow
authors.forename: Ana M
authors.initials: AM
authors.lastname: Gonzalez-Angulo
authors.forename: Sean
authors.initials: S
authors.lastname: Tunis
authors.forename: Laurence
authors.initials: L
authors.lastname: Baker
authors.forename: John
authors.initials: J
authors.lastname: Crowley
authors.forename: Patricia
authors.initials: P
authors.lastname: Deverka
authors.forename: David
authors.initials: D
authors.lastname: Veenstra
authors.forename: Gabriel N
authors.initials: GN
authors.lastname: Hortobagyi
mesh_terms: D001943:Breast Neoplasms / Q000235:genetics / Q000556:secondary / Q000628:therapy; D017326:Clinical Trials, Phase III as Topic; D003131:Combined Modality Therapy; D005260:Female; D006801:Humans; D008198:Lymph Nodes / Q000473:pathology*; D008207:Lymphatic Metastasis; D016032:Randomized Controlled Trials as Topic / Q000379:methods*