Multi‐omic molecular profiling guide's efficacious treatment selection in refractory metastatic breast cancer: a prospective phase II clinical trial. Issue 1 (12th September 2021)

• Record Type: Journal Article
• Authors: Pierobon, Mariaelena; Robert, Nicholas J.; Northfelt, Donald W.; Jahanzeb, Mohammad; Wong, Shukmei; Hodge, Kimberly A.; Baldelli, Elisa; Aldrich, Jessica; Craig, David W.; Liotta, Lance A.; Avramovic, Sanja; Wojtusiak, Janusz; Alemi, Farrokh; Wulfkuhle, Julia D.; Bellos, Angela; Gallagher, Rosa I.; Arguello, David; Conrad, Amber; Kemkes, Ariane; Loesch, David M.; Vocila, Linda; Dunetz, Bryant; Carpten, John D.; Petricoin, Emanuel F.; Anthony, Stephen P.
• Is Part Of: Molecular oncology. Volume 16:Issue 1(2022)
• Page Start: 104
• Page End: 115
• Publication Date: 2021-09-12
• Subjects: metastatic breast cancer -- multi‐omic molecular profiling -- precision medicine -- relational database -- TOPO1 inhibitors; Cancer -- Molecular aspects -- Periodicals; 616.994005
• DOI: 10.1002/1878-0261.13091
• Languages: English
• ISSNs: 1574-7891

Abstract

Abstract : This prospective phase II clinical trial (Side Out 2) explored the clinical benefits of treatment selection informed by multi‐omic molecular profiling (MoMP) in refractory metastatic breast cancers (MBCs). Core needle biopsies were collected from 32 patients with MBC at trial enrollment. Patients had received an average of 3.94 previous lines of treatment in the metastatic setting before enrollment in this study. Samples underwent MoMP, including exome sequencing, RNA sequencing (RNA‐Seq), immunohistochemistry, and quantitative protein pathway activation mapping by Reverse Phase Protein Microarray (RPPA). Clinical benefit was assessed using the previously published growth modulation index (GMI) under the hypothesis that MoMP‐selected therapy would warrant further investigation for GMI ≥ 1.3 in ≥ 35% of the patients. Of the 32 patients enrolled, 29 received treatment based on their MoMP and 25 met the follow‐up criteria established by the trial protocol. Molecular information was delivered to the tumor board in a median time frame of 14 days (11–22 days), and targetable alterations for commercially available agents were found in 23/25 patients (92%). Of the 25 patients, 14 (56%) reached GMI ≥ 1.3. A high level of DNA topoisomerase I (TOPO1) led to the selection of irinotecan‐based treatments in 48% (12/25) of the patients. A pooled analysis suggested clinical benefit in patients with high TOPO1 expression receiving irinotecan‐based regimens (GMI ≥ 1.3 in 66.7% of cases). These results confirmed previous observations that MoMP increases the frequency of identifiable actionable alterations (92% of patients). The MoMP proposed allows the identification of biomarkers that are frequently expressed in MBCs and the evaluation of their role as predictors of response to commercially available agents. Lastly, this study confirmed the role of MoMP for informing treatment selection in refractory MBC patients: more than half of the enrolled patients reached a GMI ≥ 1.3 even after multiple lines of previous therapies for metastatic disease. Abstract : This prospective trial assessed the role of multi‐omic molecular profiling in informing treatment selection for metastatic breast cancer patients. Molecular profiles were collected in 14 business days and targetable alterations for commercial agents were identified in 92% of patients; 56% of patients reached a growth modulation index ≥ 1.3 after multiple lines of previous therapies. This work confirms the unique role for multi‐omic molecular profiling in guiding treatment selection for metastatic patients.