| Title: |
Prediction of dose reductions and impact of reduced starting doses of CDK4 /6i on effectiveness in HR ‐positive/ HER2 ‐negative metastatic breast cancer: Real‐world data from the OPAL registry |
| Authors: |
Marschner, Patrick; Ringwald, Kai; Thill, Marc; Schock, Caroline; Kruggel, Lisa; Kaltenecker, Gabriele; Rodemer, Yolanda; Zahn, Mark‐Oliver; Klein, Dunja; Welt, Anja; Nusch, A.; Hagen, Volker; Kaiser‐Osterhues, Anja; Haug, Nina; Stickeler, Elmar; Harbeck, Nadia; Wöckel, Achim; Marschner, Norbert; Decker, Thomas; OPAL Registry Group, Study group |
| Source: |
International journal of cancer. - (2026) , ISSN: 1097-0215 |
| Publication Year: |
2026 |
| Collection: |
University of Freiburg: FreiDok |
| Description: |
Cancer patients prone to toxicities might benefit from dose reduction over fixed-dose recommendations. We develop a predictive index to identify patients with increased probability of dose reduction, intolerable toxicities, or therapy discontinuation (hereafter: dose reduction) in metastatic breast cancer (MBC) and compare real-world effectiveness of reduced (RSD) versus full starting dose (FSD) using this index. This analysis included 618 patients with HR-positive, HER2-negative MBC from the prospective, observational, multicenter registry OPAL (NCT03417115), receiving first-line palbociclib (n = 386) or ribociclib (n = 232) plus endocrine therapy. A logistic regression model was employed to derive the predictive index. Inverse probability of treatment weighting was used to emulate a head-to-head comparison of RSD and FSD by analyzing progression-free (PFS) and overall survival (OS). Within 6 months, 215 patients (35%) underwent dose reduction, including 109 (51%) with RSD. Predictors for dose reduction were age ≥65 years and Charlson comorbidity index (CCI) ≥1. Among patients with increased probability of dose reduction (index ≥1: ≥65 years and/or CCI ≥ 1), median PFS and OS were 30.1 [21.7, 54.0] and 57.6 [40.0, NA] months with RSD vs. 29.3 [24.9, 32.0] and 43.1 [38.8, 50.3] months with FSD. For low-probability patients (index = 0: |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| Relation: |
https://freidok.uni-freiburg.de/data/279138 |
| DOI: |
10.1002/ijc.70433 |
| Availability: |
https://freidok.uni-freiburg.de/data/279138; https://doi.org/10.1002/ijc.70433 |
| Accession Number: |
edsbas.4C374BB |
| Database: |
BASE |