ArticleCancer chemotherapy and pharmacology2026
Crossing the toxicity threshold: a repeated landmark analysis of early toxicities and treatment modification during first-line CDK4/6 inhibitor therapy.
Article in Cancer chemotherapy and pharmacology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
0 citing papers in PubMed.
No citing paper in PubMed yet.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundWhether early treatment-related toxicities during cyclin-dependent kinase 4/6 inhibitor (CDK4/6i) therapy reflect treatment activity or simply longer treatment exposure remains unclear. Previous studies have largely evaluated toxicities cumulatively, potentially introducing immortal time bias into toxicity-outcome associations. We evaluated the prognostic significance of early toxicities and treatment modifications using repeated landmark analyses in patients receiving first-line CDK4/6i therapy for HR+/HER2- metastatic breast cancer.
methodsThis retrospective study included 404 patients receiving first-line CDK4/6i plus endocrine therapy. Repeated landmark analyses at 8, 12, and 24 weeks evaluated associations of early toxicities and treatment modifications with subsequent progression-free survival (PFS) and overall survival (OS).
resultsDuring treatment, any-grade neutropenia occurred in 88.1% of patients, hepatotoxicity in 22.5%, QTc prolongation in 17.6%, and dose modification in 37.4%. At both the 8- and 12-week landmarks, grade 1-2 neutropenia was consistently associated with improved PFS and OS in multivariable analyses (all p<0.05; 8-week PFS: 33.2 vs. 22.1 months; OS: 90.6 vs. 40.8 months). Grade 3-4 neutropenia showed less consistent associations with survival but remained associated with improved OS at 12 weeks. Dose modification was independently associated with shorter PFS at the 12- and 24-week landmarks (all p<0.05). Associations between neutropenia and survival were attenuated at the 24-week landmark.
conclusionGrade 1-2 neutropenia was the most consistent toxicity-based predictor of favorable survival and may represent a potential clinical marker of treatment activity. Associations with grade 3-4 neutropenia were less consistent. Dose modification was associated with shorter PFS, whereas hepatotoxicity and QTc prolongation showed no consistent independent prognostic associations.
Indexed as
Identifiers
42786218What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.