Abstract GS4-03: Neoadjuvant nab-paclitaxel weekly versus dose-dense paclitaxel followed by dose-dense EC in high risk HR+/HER2- early BC by: Results from the neoadjuvant part of ADAPT HR+/HER2- trial

Abstract

Background: Pathological complete response (pCR) is associated with improved outcome in patients with high-risk HR+/HER2- breast cancer (BC) but the use of (neo)adjuvant chemotherapy in early HR+/HER2- BC remains controversial. Oncotype DX / Recurrence Score (RS) and dynamic Ki67 response after short preoperative endocrine therapy are potentially predictive for pCR. Still, no prospective data are available so far to predict chemotherapy efficacy in this key patient group. Use of dose-dense chemotherapy is associated with improved outcome in meta-analysis, but its use in the neoadjuvant setting is less studied. Furthermore, use of nab-paclitaxel instead of solvent-based paclitaxel has shown promising results in some studies. Here, we present for the first time data from a randomized prospective trial comparing these risk-selection strategies according to RS and Ki67 decrease in high-risk HR+/HER2- BC. Methods: High-risk BC patients [cN0-1 with RS>25 or (RS 12-25 AND (centrally measured) post-endocrine Ki67 >10%] OR [cN2-3 status] OR [G3 AND Ki67>40%] were randomized to (neo)adjuvant 4x paclitaxel175 q2w or 8xnab-paclitaxel 125 mg/m2q1w followed by 4x E90C600 q2w. pCR was defined as no invasive tumor in breast and lymph nodes. Results: 858 patients with available surgery data randomized to neoadjuvant Pac-EC (N=423) or nab-Pac-EC (N=435) were analyzed. Median age was 51 years; median RS was 30 (N=572); 34% had node-positive; 46% (locally) G3 tumors. Baseline characteristics were well balanced between study arms. Patients receiving nab-Pac-EC had higher pCR than those with Pac-EC (20.3% vs. 12.3%, p=.002); patients with RS<25 (about 27%) had a lower pCR rate than those with RS>25 (6.5% vs. 15.8%, p=.003). The association of RS with pCR appeared more pronounced in premenopausal women, but a test of interaction was not significant; RS was about 3 points higher (mean 32.9 vs. 29.8, p<.001) in postmenopausal cases (p=.001). Clinical tumor stage cT2-4 was reported in 65%, with a lower pCR rate than in cT1 tumors (14% vs. 20%, p=.02). RS was moderately correlated (R=.45) with baseline Ki67. In multivariable analysis with tumor stage, RS, Ki67, menopausal status, and ER and PR positivity, higher RS and cT1 stage were favorable for pCR. Excluding RS, higher Ki67 and lower ER (as well as cT1) were favorable. In patients with RS<25, there was no pCR with Pac-EC (0/72 pCR); pCR was almost 20% with RS>25 and nab-Pac-EC. Further details and data including impacts of Ki67 dynamics and additional markers on pCR will be presented at the meeting. Conclusions: Use of neoadjuvant nab-paclitaxel instead of solvent-based paclitaxel appears promising within a short (16-weeks) dose-dense chemotherapy schedule in high-risk HR+/HER2- BC. For the first time, data from a large neoadjuvant randomized trial confirm RS could help to select patients for neoadjuvant chemotherapy in high-risk HR+/HER2- breast cancer (BC). Citation Format: Sherko Kuemmel, Oleg Gluz, Ulrike Nitz, Michael Braun, Matthias Christgen, Kerstin Luedtke-Heckenkamp, Raquel von Schumann, Maren Darsow, Helmut Forstbauer, Jochem Potenberg, Eva-Maria Grischke, Bahriye Aktas, Claudia Schumacher, Ronald Kates, Monika Graeser, Rachel Wuerstlein, Christoph Uleer, Michael Hauptmann, Steve Shak, Rick Baehner, Hans Kreipe, Nadia Harbeck, West German Study Group. Neoadjuvant nab-paclitaxel weekly versus dose-dense paclitaxel followed by dose-dense EC in high risk HR+/HER2- early BC by: Results from the neoadjuvant part of ADAPT HR+/HER2- trial [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr GS4-03.

The clinical utility of gene expression assays in breast cancer patients with 0–3 involved lymph nodes

“…In multivariable analysis, only RS and tumor size predicted for pCR, demonstrating that RS can be used to select HR+ HER2 negative BCA patients for neoadjuvant chemotherapy. 19 The adjuvant endocrine portion of ADAPT demonstrated noninferior 5-year iDFS for ET-responsive patients with RS of 12-25 and Ki67 ⩽ 10% after ET compared with patients with RS ⩽ 11 [92.6% (95% CI 90.8%, 94.0%) versus 93.9% (95% CI 91.8, 95.4%), respectively], which met prespecified criteria for noninferiority, thereby meeting the primary trial endpoint. 5-year distant DFS [95.6% (95% CI 94.2%, 96.7%) versus 96.3% (95% CI 94.6%, 97.5%) p = 0.247, respectively] and 5-year OS [97.3% (95% CI 96.1%, 98.1%) versus 98.0% (95% CI 96.7%, 98.9%), respectively] were also similar.…”

“…In multivariable analysis, only RS and tumor size predicted for pCR, demonstrating that RS can be used to select HR+ HER2 negative BCA patients for neoadjuvant chemotherapy. 19…”

Update Breast Cancer 2021 Part 1 – Prevention and Early Stages

“…Also in the ADAPT study HR+ HER2− patients were selected for a neoadjuvant chemotherapy based on a multigene test (Onco-typeDX ® ) and a Ki-67 assessment after a 3-week endocrine treatment [60]. Eligible for neoadjuvant chemotherapy were patients with a recurrence score of > 25 or more than 3 positive lymph nodes and patients with > 10 % Ki-67 positive cells in the repeat core needle biopsy 3 weeks after endocrine treatment [60].…”

“…Also in the ADAPT study HR+ HER2− patients were selected for a neoadjuvant chemotherapy based on a multigene test (Onco-typeDX ® ) and a Ki-67 assessment after a 3-week endocrine treatment [60]. Eligible for neoadjuvant chemotherapy were patients with a recurrence score of > 25 or more than 3 positive lymph nodes and patients with > 10 % Ki-67 positive cells in the repeat core needle biopsy 3 weeks after endocrine treatment [60]. Patients were randomised into one of two arms: 4 cycles of paclitaxel 175 mg/m 2 every 2 weeks followed by 4 cycles of epirubicin/cyclophosphamide every 2 weeks versus 8 cycles of Nab-paclitaxel 125 mg/m 2 weekly followed by 4 cycles of epirubicin/cyclophosphamide every 2 weeks.…”

“…Patients were randomised into one of two arms: 4 cycles of paclitaxel 175 mg/m 2 every 2 weeks followed by 4 cycles of epirubicin/cyclophosphamide every 2 weeks versus 8 cycles of Nab-paclitaxel 125 mg/m 2 weekly followed by 4 cycles of epirubicin/cyclophosphamide every 2 weeks. In the paclitaxel arm, the pCR rate was 12.9 % and in the Nab-paclitaxel arm 20.8 % (p = 0.002) [60]. Thus, after demonstrating better efficacy of Nab-paclitaxel versus paclitaxel in the neoadjuvant treatment of TNBC patients [61], it has now also been shown in HER2−, HR+ patients that the pCR rate could be almost doubled [61].…”