355P - Reduction of anthracycline use with a combined imaging and pathology prediction model in the neoadjuvant I-SPY2 trial

Background

The I-SPY2 Trial is a randomized phase II platform trial testing novel neoadjuvant therapies. Serial MRI and pathology are used to evaluate response. New agents (+/- taxane) are tested in a 12 week (wk) treatment block, followed by Adriamycin/Cytoxan (AC). We sought to determine whether MRI functional tumor volume (FTV)-based predictive models, in conjunction with breast core biopsy, could identify early responders who had reached pCR and thus proceed to surgery without receiving AC, sparing them additional toxicity. The “predicted Residual Cancer Burden” (preRCB) models were developed using retrospective I-SPY data and prospectively tested in I-SPY2.

Methods

Eligible patients (pts) were required to be on preRCB-designated treatment arms and consented to participate in the optional preRCB process. PreRCB included breast MRI at baseline, wk 3 and wk 12 of the initial I-SPY2 treatment block and a clinical core biopsy of the tumor bed at 12-weeks. Pts who met combined preRCB criteria (predicted probability of pCR above threshold in a subtype specific FTV model and no invasive tumor on breast biopsy) were eligible to proceed to surgery without AC after return of results (ROR) and consultation with their clinician.

Results

From 1/20-6/22, 172 pts underwent preRCB and completed surgery. 51/172 (30%) met combined MRI/biopsy preRCB criteria and 40/51 proceeded to surgery without AC (Table). 96% (49/51) pts who met preRCB criteria had RCB0/1 vs. 48% (57/120) of pts who did not meet criteria (OR 27 [6.5-235]; Fisher’s exact test p=1.04E-10). Overall, preRCB led to a 24% reduction in AC use without significant difference in RCB0/1 rate between those with and without AC (p=1).

Conclusions

Implementation of preRCB in I-SPY2 identified patients with pCR prior to AC. High uptake of early surgery recommendations led to reduced use of AC while maintaining optimal outcome. I-SPY 2.2 is testing next-generation models to enable further optimization. Table: 355P

Clinical trial identification

NCT01042379.

Editorial acknowledgement

Legal entity responsible for the study

Quantum Leap Healthcare Collaborative.

Funding

Research reported in this abstract was supported by the National Cancer Institute of the National Institutes of Health under award number P01CA210961. The authors wish to acknowledge the generous support of the study sponsors, Quantum Leap Healthcare Collaborative ( QLHC, 2013 to present) and the Foundation for the National Institutes of Health (2010 to 2012).

Disclosure

D. Yee: Financial Interests, Personal, Research Funding, unrelated to this work: Boehringer Ingelheim. C. Isaacs: Financial Interests, Institutional, Research Grant: Tesaro/GSK, Seattle Genetics, Pfizer, AstraZeneca, BMS, Genentech, Novartis; Financial Interests, Personal, Licencing Fees or royalty for IP: UptoDate, McGrawHill; Financial Interests, Personal, Speaker, Consultant, Advisor: AstraZeneca, Genentech, ION, Novartis, Pfizer, Seagen; Financial Interests, Personal, Advisory Board: Novartis; Non-Financial Interests, Personal, Leadership Role: SideOut Foundation . H.S. Rugo: Financial Interests, Personal, Other, Consultancy/advisory support: PUMA, NAPO, Mylan, Daiichi Sankyo, Eisai; Financial Interests, Institutional, Local PI: Novartis, Lilly, Pfizer, Daiichi, AstraZeneca, Gilead Sciences, Inc., GSK, Sermonix Pharmaceuticals Ins., Pionyr Immunotherapeutics, Taiho Oncology, Inc., Veru Inc; Financial Interests, Institutional, Coordinating PI: OBI Pharma, Astellas Pharma Inc., F. Hoffmann-La Roche AG/Genentech, Inc., Merck; Financial Interests, Personal, Other, Travel support to academic meetings: Merck, AstraZeneca, Gilead; Non-Financial Interests, Advisory Role, I advise a number of companies without compensation: various. L.J. Van't Veer: Financial Interests, Personal, Stocks or ownership: Agenda NV. N. Hylton: Financial Interests, Institutional, Research Funding: NIH. L. Esserman: Financial Interests, Institutional, Research Funding: Merck; Financial Interests, Personal, Advisory Board: Blue Cross Blue Shield; Financial Interests, Personal, Other, Website Author: UpToDate. All other authors have declared no conflicts of interest.