In:
Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 38, No. 15_suppl ( 2020-05-20), p. 515-515
Abstract:
515 Background: HR+/HER2+ breast cancer (BC) is a distinct entity associated with better prognosis compared to HR-/HER2+ BC. However, combination of chemotherapy (CT) with (dual) anti-HER2 blockade is standard in HER2+ early BC (EBC), irrespective of HR-status. Despite of some promising data on combination of endocrine therapy (ET) with dual anti-HER2 blockade in EBC and metastatic HR+/HER2+ BC, no prospective comparison of neoadjuvant CT vs. ET + dual HER2-blockade has yet been performed. Methods: In the prospective WSG TP-II phase II-trial (NCT03272477; Sponsor: Palleos GmbH, Wiesbaden, Germany), 207 patients (pts) (257 screened; 40 centers) with centrally confirmed HR+/HER2+ EBC were randomized to 12 weeks of standard ET (n=100) vs. paclitaxel 80 mg/m 2 weekly (n=107) +trastuzumab+pertuzumab q3w for all pts. Primary endpoint was pCR (ypT0/is/ypN0). Secondary endpoints include safety, disease-free and overall survival, translational research, and quality of life (QoL). Omission of further CT was allowed in all pts with pCR; dual HER2-blockade was administered in the adjuvant setting in all pts. Results: Baseline characteristics were well balanced between the arms. Median age was 53 years; 58% had cT2-4, 28% had cN+; 43% had G3 tumors. pCR data were available in 198 pts (ET: n=96; Pac: n=102). pCR was observed in 24% (95% CI: 16-34%) with ET+T+P vs. 57% (95% CI:47-67%) with Pac+T+P (OR 0.24, 95% CI: 0-0.46, p 〈 0.001). In multivariable logistic regression analysis and corresponding sensitivity analysis (bootstrap/subsample inclusion frequencies and lasso regression) including study arm, BMI, menopausal, cT, and cN status, histological grade, HER2-status, Ki67, ER, PR as continuous variables, only study arm and HER2 3+ status were significantly associated with pCR. Neoadjuvant treatment was well tolerated in both study arms and completed per protocol in 93/92 (ET+P+T/Pac+P+T) patients. Only 9/13 SAEs (ET+P+T/Pac+P+T) were reported during neoadjuvant therapy. PAM50 and QoL analysis are ongoing. Conclusions: WSG TP-II is the first randomized prospective trial comparing two neoadjuvant de-escalation treatments in HR+/HER2+ EBC. The excellent pCR rate of 57% after only 12 weeks of Pac+P+T was clearly superior to the still promising 24% pCR rate in pts treated by ET+P+T. In both arms, treatment efficacy was most pronounced in HER2 3+ tumors. Survival results need to be awaited before definite recommendations for a de-escalated regimen in HR+/HER2+ EBC can be made. Clinical trial information: 2016-005157-21 .
Type of Medium:
Online Resource
ISSN:
0732-183X
,
1527-7755
DOI:
10.1200/JCO.2020.38.15_suppl.515
Language:
English
Publisher:
American Society of Clinical Oncology (ASCO)
Publication Date:
2020
detail.hit.zdb_id:
2005181-5
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