Abstract P4-15-01: Distinct early proliferation response to neoadjuvant anti-HER2 antibody drug conjugate +/- endocrine therapy in early breast cancer in the WSG ADAPT HER2+/HR+ trial

Autor: Rachel Wuerstlein, Oleg Gluz, Daniel Hofmann, Michael Braun, Helmut Forstbauer, Bahriye Aktas, Ronald E. Kates, J. Potenberg, Claudia Schumacher, Nadia Harbeck, Kuemmel Sherko, Hans Kreipe, Matthias Christgen, Ulrike Nitz, Toralf Reimer, Peter A. Fasching, Kraemer Stefan
Rok vydání: 2015
Předmět:
Zdroj: Cancer Research. 75:P4-15
ISSN: 1538-7445
0008-5472
Popis: Background: HER2+, hormone receptor-positive (HR+) breast cancer is a distinct subtype associated with good prognosis but poor response to standard chemotherapy + anti-HER2 (single or dual blockade). Substantial overtreatment by poly-chemotherapy combined with anti-HER2 therapy is suspected in this subtype. Yet, the efficacy of combining endocrine therapy (ET) with anti-HER2 therapy or novel antibody drug conjugates like T DM1 without systemic chemotherapy remains unclear. Methods: ADAPT HER2+/HR+ is a phase II, randomized, neoadjuvant, 3-arm trial (12 weeks) in patients with cT1c-cT3, cN0/+ HER2+, ER+ and/or PR+ early BC. Arm A: T-DM1 (3.6 mg/kg) alone; Arm B: T DM1 + ET (premenopausal: tamoxifen, postmenopausal: AI); Arm C: trastuzumab + ET. Postoperative chemotherapy is recommended together with completion of one year of trastuzumab. Initial and serial core biopsies were obtained prior to therapy and after 3 weeks. First translational analysis of the trial run-in phase (n=130) focuses on dynamics of HER2, Ki67, ER and PR. Results: 162 tumors, HR+ and HER2+ by local pathology, were screened; n=130 were HR+ and HER2+ by central pathology and randomized at 40 trial sites in Germany between 11/2012 and 03/2014 (Arm A/B/C: 37/49/44). Median age was 49 years; 60% were cT2-3, 32% cN+, 75% central G3; median baseline Ki67 was 30%; 49 patients were treated by TAM and 44 postmenopausal patients by AI in ET containing arms. Three-week core biopsies were available in 117 patients (arm A/B/C: n=33/43/41), n=99 with invasive tumor tissue (61/76 (80%) in T-DM1 containing arms and 38/41(93%) in trastuzumab + ET arm). Three-week Ki67 could only be analyzed in n=73 (53% of patients in T-DM1-containing arms, 81% in the T+ET arm) due to a lacking amount of cells for counting ( Median fractional decrease in proliferation (Ki67) after 3 weeks of therapy was 40% in the T-DM1 + ET arm (B) as compared to 14% and 25% in the T-DM1 (A) and T+ET (C) arms, respectively. Among postmenopausal patients, the contrast (52% (B) vs. 0% (A) and 28% (B)) was significant. Mean PR expression change (absolute, measured in %) was -15 in the B Arm vs. 7 and -7 in the A and C arms, respectively (p=0.04) – particularly in postmenopausal women ( 25 vs. +13 and -10, respectively, p=0.04). Baseline ER expression was positively associated with early proliferation response (fractional Ki67 decrease), e.g., by logistic regression using 30% decrease as response criterion. Data on the impact of gene mutations and further molecular markers on proliferation response will be available for presentation at the meeting. Conclusions: In the unique neoadjuvant ADAPT HER2+/HR+ trial, the combination of T-DM1 with ET (particularly AI) seems to be associated with a strong early proliferation response and PR expression drop in anti-HER2 antibody (drug conjugate) +/- ET, without systemic pre-operative chemotherapy. Interim analysis is scheduled after 130 completely treated patients. The high percentage of non-invasive tissue biopsied after 3 weeks in the T-DM1 arms is intriguing, as it would be consistent with higher pathological complete response rates. Citation Format: Oleg Gluz, Ulrike Nitz, Kuemmel Sherko, Kraemer Stefan, Michael Braun, Claudia Schumacher, Bahriye Aktas, Helmut Forstbauer, Toralf Reimer, Peter Fasching, Jochem Potenberg, Daniel Hofmann, Ronald E Kates, Rachel Wuerstlein, Matthias Christgen, Hans H Kreipe, Nadia Harbeck. Distinct early proliferation response to neoadjuvant anti-HER2 antibody drug conjugate +/- endocrine therapy in early breast cancer in the WSG ADAPT HER2+/HR+ trial [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P4-15-01.
Databáze: OpenAIRE
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