Abstract PD1-01: Durvalumab (MEDI4736) concurrent with nab-paclitaxel and dose dense doxorubicin cyclophosphamide (ddAC) as neoadjuvant therapy for triple negative breast cancer (TNBC)
Authors: Pusztai Lajos , Reisenbichler Emily , Bai Yailai , Fischbach Neal , Persico Justin , Adelson Kerin , Katoch Anamika , Horowitz Nina , Lannin Donald , Killelea Brigid , Chagpar Anees , Frederick Courtney , Burello Trisha , Blenman Kim , Rimm David , Silber Andrea 
Published: March 2020

Abstract
Background: The goal of this Phase I/II trial (NCT02489448) was to assess the safety and efficacy of concurrent durvalumab with weekly nab-paclitaxel (100 mg/m2) x 12 followed by ddAC x 4 as neoadjuvant therapy for stage I-III TNBC and to identify biomarkers of response. The primary efficacy endpoint was pathologic complete response (pCR: ypT0,is/N0). Methods: The Phase I portion of the trial assessed two dose levels of durvalumab 3 and 10 mg/kg q 2 weeks. The trial followed Simon’s two step design, with early stopping for futility if &lt; 7 of the first 20 patients achieve pCR. PD-L1 expression on pretreatment biopsies was assessed with chromogenic immunohistochemistry using the SP263 antibody. PD-L1 positivity was determined by consensus review of 2 pathologists (E.R., D.R.) and staining &gt;1 % on immune and tumor cells was considered positive. Tumor infiltrating lymphocyte (TIL) count was assessed on H&E stained slides using QuPath v0.2.0 open source digital image analysis software platform and a breast cancer specific scoring algorithm (CL11NN). TIL count was expressed as TIL:TIL+Tumor cells x 100. Results: 57 patients were enrolled and evaluable (n=4 at 3 mg/kg, n=53 at 10 mg/kg dose). No dose limiting toxicities were observed during the Phase I portion, the final pCR rate is 44% (95% CI:30%-57%). 18 patients (31%) experienced grade 3/4 adverse events (AE), most frequently neutropenia (n=5). Possibly immune related grade 3 or 4 AEs included Guillain-Barre syndrome (n=1), hypothyroidism (n=1), colitis (n=1), hyperglycemia (n=1). 14 (24%) patients received &lt; 9 of the planned 12 cycles of durvalumab. No perioperative adverse events were seen. Fifty patients had baseline PD-L1 IHC results available (n=7 QC failure), 19 (38%) were PD-L1 positive. The pCR rates were 55% (95% CI: 36%-73%) versus 21% (95% CI: 6%-45%) in the PDL-1 positive and negative groups, respectively (p=0.03). Digital stromal TIL counts were available on 52 patients, there was no significant difference in TIL count between the response groups. Conclusion: Concomitant administration of durvalumab with weekly nab-paclitaxel and sequential ddAC neoadjuvant chemotherapy resulted in a pCR rate of 44%. pCR rate was higher in PD-L1 positive patients (55%) than PD-L1 negative (21%) cancers.
Citation Format: Lajos Pusztai, Emily Reisenbichler, Yailai Bai, Neal Fischbach, Justin Persico, Kerin Adelson, Anamika Katoch, Nina Horowitz, Donald Lannin, Brigid Killelea, Anees Chagpar, Courtney Frederick, Trisha Burello, Kim Blenman, David Rimm, Andrea Silber. Durvalumab (MEDI4736) concurrent with nab-paclitaxel and dose dense doxorubicin cyclophosphamide (ddAC) as neoadjuvant therapy for triple negative breast cancer (TNBC) [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr PD1-01.