Abstract P2-16-09: Residual cancer burden in patients with early stage triple negative breast cancer who progress on anthracycline-based neoadjuvant chemotherapy in an ongoing clinical trial (ARTEMIS)
Authors: Garber Haven , Rauch Gaiane , Adrada Beatriz , Candelaria Rosalind , Mittendorf Elizabeth , Thompson Alastair , Litton Jennifer , Damodaran Senthil , Lim Bora , Arun Banu , Ueno Naoto , Valero Vicente , Ibrahim Nuhad , Murthy Rashmi , Tripathy Debu , Piwnica-Worms Helen , Symmans Fraser , Huo Lei , Moulder Stacy 
Published: March 2020

Abstract
BACKGROUND: Current treatment for early stage triple negative breast cancer (TNBC) includes neoadjuvant systemic chemotherapy (NAST), which is used to assess disease biology and the need for adjuvant treatment in case of residual disease at the time of surgery, also known as residual cancer burden (RCB). Patients with TNBC who experience RCB-0 (pathologic complete response [pCR]) or RCB-I after NAST have an excellent prognosis whereas patients with significant residual disease (RCB-II or RCB-III) are at a high risk of relapse. Standard NAST for TNBC achieves pCR in 30-50% of cases. NAST typically consists of anthracycline-based chemotherapy followed or preceded by a taxane +/- carboplatin. Disease progression (PD) is uncommon in TNBC patients receiving NAST and little is known regarding outcomes in patients who have PD during the initial phase of NAST. METHODS: Total 316 TNBC patients were evaluated from two prospectively accrued clinical trials of NAST (NCT02276443 and NCT01334021). The ARTEMIS trial (NCT02276443) aims to improve pCR rates by adding targeted therapy to chemotherapy as the second phase of NAST for those patients who do not experience at least a 70% volumetric reduction after 4 cycles of doxorubicin/cyclophosphamide (AC). Unique histopathologic features including % stromal tumor-infiltrating lymphocytes (sTIL), presence of mesenchymal histology (high vimentin expression by IHC), and androgen receptor expression are used to guide second phase therapy. RESULTS: 31 TNBC patients had PD while receiving AC as the first phase of NAST (10%; 95% CI= 6.69-13.31%). 9 of 31 patients proceeded to standard chemotherapy and all had RCB II/III disease. 22 of 31 patients were enrolled to targeted therapy trials. 6 were treated with the EGFR inhibitor panitumumab + carboplatin/paclitaxel, 9 with atezolizumab + nab-paclitaxel, and 7 with everolimus, bevacizumab, and liposomal doxorubicin (DAE). Of these 22 patients, 3 (13.6%) had pCR/RCB-0, 1 (4.5%) RCB-I and 18 (81.8%) had RCB II/III. All 4 patients who experienced RCB-0/I had T2N0 disease at diagnosis. 2 had sTIL &lt; 5% and 2 patients had 70% sTIL. CONCLUSION: PD is uncommon while receiving NAST. Patients with TNBC and progression on initial NAST with AC are unlikely to achieve pCR or RCB-I status despite subsequent standard chemotherapy. Combination chemotherapy with targeted therapy on clinical trial resulted in a numerically higher rate of pCR+RCB-I (18%) as salvage therapy, but this was not statistically significant and requires confirmation in larger trials.
Citation Format: Haven Garber, Gaiane Rauch, Beatriz Adrada, Rosalind Candelaria, Elizabeth Mittendorf, Alastair Thompson, Jennifer Litton, Senthil Damodaran, Bora Lim, Banu Arun, Naoto Ueno, Vicente Valero, Nuhad Ibrahim, Rashmi Murthy, Debu Tripathy, Helen Piwnica-Worms, Fraser Symmans, Lei Huo, Stacy Moulder. Residual cancer burden in patients with early stage triple negative breast cancer who progress on anthracycline-based neoadjuvant chemotherapy in an ongoing clinical trial (ARTEMIS) [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 P2-16-09.