| Title: |
Palbociclib plus letrozole versus weekly paclitaxel, both in combination with trastuzumab plus pertuzumab, as neoadjuvant treatment for patients with HR-positive/HER2-positive early breast cancer: primary results from the randomized phase II TOUCH trial (IBCSG 55-17). |
| Authors: |
Malorni, L; Tyekucheva, S; Gombos, A; Hasler-Strub, U; Zamagni, C; Chakiba-Brugère, C; Colleoni, M; Mueller, A; Minisini, A M; Taylor, Donatienne; Salmon, J P; Gallerani, E; Cariello, A; Fontana, A; Roschitzki-Voser, H; Kammler, R; Ruepp, B; Loi, S; Viale, G; Regan, M M; Brain, E; Biganzoli, L; International Breast Cancer Study Group (a division of ETOP IBCSG Partners Foundation) |
| Contributors: |
UCL - SSS/IREC/MONT - Pôle Mont Godinne; UCL - (MGD) Service d'oncologie médicale |
| Source: |
Annals of oncology : official journal of the European Society for Medical Oncology, (2025) |
| Publication Year: |
2025 |
| Collection: |
DIAL@USL-B (Université Saint-Louis, Bruxelles) |
| Subject Terms: |
CDK4/6 inhibitor; HER2 positive; chemotherapy de-escalation; early breast cancer; hormone receptor positive; neoadjuvant therapy |
| Description: |
Hormone receptor (HR)-positive/human epidermal growth factor receptor 2 (HER2)-positive breast cancer (BC) is a heterogeneous disease with low pathological complete response (pCR) to standard neoadjuvant treatment. Cyclin-dependent kinase 4 and 6 inhibitors with endocrine and anti-HER2 therapy have shown a potential for chemotherapy omission in this context. TOUCH is an international, open-label, phase II trial for postmenopausal patients with cT >1 cm, cN0 or cN1, HR-positive/HER2-positive BC, randomly assigned 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 absolute intrinsic molecular subtyping Treatment-by-biomarker interaction was estimated using logistic regression in 115 assessable patients. A total of 147 patients were randomly assigned (74 paclitaxel + HP, 73 palbociclib + letrozole + HP) and 145 constituted the treated population, with a median age of 69 years (interquartile range 63-73 years). More patients completed palbociclib versus paclitaxel (94.4% versus 79.5%). The most frequent grade 3-4 adverse events were neutropenia and diarrhea (6.9% versus 43.1% and 11% versus 8.3% in the paclitaxel + HP versus the palbociclib + letrozole + HP groups, respectively). The pCR rate was 32.9% [95% confidence interval (CI) 22.3% to 44.9%] in the paclitaxel + HP group and 33.3% (95% CI 22.7% to 45.4%) in the palbociclib + letrozole + HP group. No significant treatment-by-RBsig interaction was observed (P = 0.18): pCR in RBsig high versus low was 31.3% (95% CI 16.1% to 50.0%) versus 42.3% (95% CI 23.4% to 63.1%) in the paclitaxel + HP group, and 38.5% (95% CI 20.2% ... |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| Relation: |
boreal:308536; https://hdl.handle.net/2078.1/308536; info:pmid/41109527 |
| DOI: |
10.1016/j.annonc.2025.10.016 |
| Availability: |
https://hdl.handle.net/2078.1/308536; https://doi.org/10.1016/j.annonc.2025.10.016 |
| Rights: |
info:eu-repo/semantics/openAccess |
| Accession Number: |
edsbas.8551A549 |
| Database: |
BASE |