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Adaptive Randomization of Veliparib-Carboplatin Treatment in Breast Cancer. | LitMetric

Adaptive Randomization of Veliparib-Carboplatin Treatment in Breast Cancer.

N Engl J Med

From University of California, San Francisco (UCSF) (H.S.R., C.Y., L.J.V., M.B.B., N.M.H., A.J.C., C.E., J.L., S.E.D., G.L.H., L.J.E.), and QuantumLeap Healthcare Collaborative (M.P.), San Francisco, Buck Institute for Research and Aging, Novato (C.Y.), University of California, Davis, Davis (M.H.), University of California San Diego, San Diego (A.M.W., R.S.), and University of Southern California, Los Angeles (D.T.) - all in California; University of Chicago (O.I.O., R.N.), and Loyola University (K.S.A.), Chicago; University of Pennsylvania, Philadelphia (A.D.); Gemini Group, Ann Arbor, MI (J.P.); University of Texas M.D. Anderson Cancer Center, Houston (W.F.S., L.P., S.L.M., D.A.B.), UT Southwestern Medical Center, Dallas (D.M.E., B.B.H.), and Berry Consultants, Austin (A.S., D.A.B.) - all in Texas; University of Minnesota, Minneapolis (D.Y.), and Mayo Clinic, Rochester (J.C.B., T.C.H.) - both in Minnesota; Swedish Medical Center, Seattle (H.G.K.); Georgetown Lombardi Comprehensive Cancer Center, Washington, DC (M.C.L., C.I.); University of Kansas, Lawrence (Q.J.K.); University of Arizona, Tucson (J.E.L., R.K.V.), and Mayo Clinic, Scottsdale (D.W.N.) - both in Arizona; Oregon Health and Sciences University, Portland (S.Y.C., K.A.K.); University of Denver, Denver (A.D.E.); Inova Fairfax Hospital, Falls Church, VA (K.K.E.); and Emory University, Atlanta (W.C.W.).

Published: July 2016

AI Article Synopsis

  • The I-SPY 2 trial is a phase 2 study aimed at finding effective treatments for breast cancer by matching experimental therapies with specific cancer subtypes based on genetic markers.
  • The trial evaluates the combination of veliparib, a PARP inhibitor, with carboplatin, especially in HER2-negative breast cancer cases, focusing on measuring the primary outcome of pathological complete response.
  • Results indicate a very high predicted success rate of 88% for the veliparib-carboplatin regimen in triple-negative breast cancer, with 72 patients receiving this treatment compared to 44 on standard control therapy.

Article Abstract

Background: The genetic and clinical heterogeneity of breast cancer makes the identification of effective therapies challenging. We designed I-SPY 2, a phase 2, multicenter, adaptively randomized trial to screen multiple experimental regimens in combination with standard neoadjuvant chemotherapy for breast cancer. The goal is to match experimental regimens with responding cancer subtypes. We report results for veliparib, a poly(ADP-ribose) polymerase (PARP) inhibitor, combined with carboplatin.

Methods: In this ongoing trial, women are eligible for participation if they have stage II or III breast cancer with a tumor 2.5 cm or larger in diameter; cancers are categorized into eight biomarker subtypes on the basis of status with regard to human epidermal growth factor receptor 2 (HER2), hormone receptors, and a 70-gene assay. Patients undergo adaptive randomization within each biomarker subtype to receive regimens that have better performance than the standard therapy. Regimens are evaluated within 10 biomarker signatures (i.e., prospectively defined combinations of biomarker subtypes). Veliparib-carboplatin plus standard therapy was considered for HER2-negative tumors and was therefore evaluated in 3 signatures. The primary end point is pathological complete response. Tumor volume changes measured by magnetic resonance imaging during treatment are used to predict whether a patient will have a pathological complete response. Regimens move on from phase 2 if and when they have a high Bayesian predictive probability of success in a subsequent phase 3 neoadjuvant trial within the biomarker signature in which they performed well.

Results: With regard to triple-negative breast cancer, veliparib-carboplatin had an 88% predicted probability of success in a phase 3 trial. A total of 72 patients were randomly assigned to receive veliparib-carboplatin, and 44 patients were concurrently assigned to receive control therapy; at the completion of chemotherapy, the estimated rates of pathological complete response in the triple-negative population were 51% (95% Bayesian probability interval [PI], 36 to 66%) in the veliparib-carboplatin group versus 26% (95% PI, 9 to 43%) in the control group. The toxicity of veliparib-carboplatin was greater than that of the control.

Conclusions: The process used in our trial showed that veliparib-carboplatin added to standard therapy resulted in higher rates of pathological complete response than standard therapy alone specifically in triple-negative breast cancer. (Funded by the QuantumLeap Healthcare Collaborative and others; I-SPY 2 TRIAL ClinicalTrials.gov number, NCT01042379.).

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5259561PMC
http://dx.doi.org/10.1056/NEJMoa1513749DOI Listing

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