Palbociclib plus letrozole versus weekly paclitaxel, both in combination with trastuzumab plus pertuzumab, as neoadjuvant treatment for patients with HR+/HER2+ early breast cancer: primary results from the randomized phase II TOUCH trial (IBCSG 55-17)
- Author(s)
- Malorni, L; Tyekucheva, S; Gombos, A; Hasler-Strub, U; Zamagni, C; Chakiba-Brugère, C; Colleoni, M; Mueller, A; Minisini, AM; Taylor, D; Salmon, JP; Gallerani, E; Cariello, A; Fontana, A; Roschitzki-Voser, H; Kammler, R; Ruepp, B; Loi, S; Viale, G; Regan, MM; Brain, E; Biganzoli, L; International Breast Cancer Study Group (a division of ETOP IBCSG Partners Foundation); TOUCH Trial (IBCSG 55-17) Investigators;
- Journal Title
- Annals of Oncology
- Publication Type
- Online publication before print
- Abstract
- BACKGROUND: HR+/HER2+ breast cancer (BC) is a heterogeneous disease with low pathological complete response (pCR) to standard neoadjuvant treatment. CDK4/6 inhibitors with endocrine and anti-HER2 therapy have shown a potential for chemotherapy omission in this context. PATIENTS AND METHODS: TOUCH is an international, open-label, phase II trial for postmenopausal patients with cT>1 cm, cN0 or cN1, HR+/HER2+ BC, randomized to 16 weeks of neoadjuvant weekly paclitaxel or palbociclib and letrozole, both with trastuzumab+pertuzumab (HP). The primary objective investigated the interaction between a gene-signature of E2F-pathway-activity (RBsig) and pCR (ypT0N0 or ypTisN0), hypothesizing higher pCR for RBsig high tumors in the paclitaxel+HP group, and for RBsig low tumors in the palbociclib+letrozole+HP group. RBsig was assessed by RNA-sequencing from pre-treatment biopsies; intrinsic subtypes were estimated by AIMS. Treatment-by-biomarker interaction was estimated using logistic regression in 115 assessable patients. RESULTS: 147 patients were randomized (74 paclitaxel+HP, 73 palbociclib+letrozole+HP) and 145 constituted the treated population, with a median age of 69 years (IQR 63,73). More patients completed palbociclib vs paclitaxel (94.4% vs 79.5%). The most frequent grade 3-4 adverse events were neutropenia and diarrhea (6.9% vs 43.1% and 11% vs 8.3% in the paclitaxel+HP vs the palbociclib+letrozole+HP groups, respectively). pCR rate was: 32.9% (95% CI: 22.3%-44.9%) in the paclitaxel+HP group and 33.3% (95% CI: 22.7%-45.4%) in the palbociclib+letrozole+HP group. No significant treatment-by-RBsig interaction was observed (p=0.18): pCR in RBsig high vs low was 31.3% (95% CI: 16.1%-50.0%) vs 42.3% (95% CI: 23.4%-63.1%) in the paclitaxel+HP group, and 38.5% (95% CI: 20.2%-59.4%) vs 25.8% (95% CI: 11.9%-44.6%) in the palbociclib group. pCR was higher in non-luminal vs luminal subtypes (45.5% vs 18.4%), with no interaction with treatment. CONCLUSIONS: Although the primary hypothesis was not supported, TOUCH shows that dual anti-HER2 blockade with a chemotherapy-free backbone of palbociclib+letrozole yields pCR rates similar to paclitaxel, representing an attractive alternative treatment strategy.
- Keywords
- CDK4/6 inhibitor; Early breast cancer; HER2 positive; Hormone receptor positive; RBsig; chemotherapy de-escalation; gene expression signatures; neoadjuvant therapy; post-menopausal
- Department(s)
- Medical Oncology
- Publisher's Version
- https://doi.org/10.1016/j.annonc.2025.10.016
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- Refer to copyright notice on published article.
Creation Date: 2025-11-13 02:49:17
Last Modified: 2025-11-13 02:49:45