Longitudinal tumor fraction trajectories predict risk of progression in metastatic HR<sup>+</sup> breast cancer patients undergoing CDK4/6 treatment

Dandachi, Nadia; Posch, Florian; Graf, Ricarda; Suppan, Christoph; Klocker, Eva Valentina; Müller, H; Lindenmann, Jörg; Terbuch, Angelika; Heitzer, Ellen; Balić, Marija

doi:10.1002/1878-0261.12870

Cited by 12 publications

(10 citation statements)

References 27 publications

(36 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Although some patients might initially show short-term responses before progression, others may demonstrate a delayed response. Therefore, a continuous monitoring at several time points may harbor important dynamic information 30 and might better reflect the pathologic response.…”

Section: Discussionmentioning

confidence: 99%

Dynamic Changes of Circulating Tumor DNA Predict Clinical Outcome in Patients With Advanced Non–Small-Cell Lung Cancer Treated With Immune Checkpoint Inhibitors

Weber

Leest

Donker

et al. 2021

JCO Precision Oncology

Self Cite

View full text Add to dashboard Cite

PURPOSE Immune checkpoint inhibitors (ICIs) are increasingly being used in non–small-cell lung cancer (NSCLC), yet biomarkers predicting their benefit are lacking. We evaluated if on-treatment changes of circulating tumor DNA (ctDNA) from ICI start (t0) to after two cycles (t1) assessed with a commercial panel could identify patients with NSCLC who would benefit from ICI. PATIENTS AND METHODS The molecular ctDNA response was evaluated as a predictor of radiographic tumor response and long-term survival benefit of ICI. To maximize the yield of ctDNA detection, de novo mutation calling was performed. Furthermore, the impact of clonal hematopoiesis (CH)–related variants as a source of biologic noise was investigated. RESULTS After correction for CH-related variants, which were detected in 75 patients (44.9%), ctDNA was detected in 152 of 167 (91.0%) patients. We observed only a fair agreement of the molecular and radiographic response, which was even more impaired by the inclusion of CH-related variants. After exclusion of those, a ≥ 50% molecular response improved progression-free survival (10 v 2 months; hazard ratio [HR], 0.55; 95% CI, 0.39 to 0.77; P = .0011) and overall survival (18.4 v 5.9 months; HR, 0.44; 95% CI, 0.31 to 0.62; P < .0001) compared with patients not achieving this end point. After adjusting for clinical variables, ctDNA response and STK11/ KEAP1 mutations (HR, 2.08; 95% CI, 1.4 to 3.0; P < .001) remained independent predictors for overall survival, irrespective of programmed death ligand-1 expression. A landmark survival analysis at 2 months (n = 129) provided similar results. CONCLUSION On-treatment changes of ctDNA in plasma reveal predictive information for long-term clinical benefit in ICI-treated patients with NSCLC. A broader NSCLC patient coverage through de novo mutation calling and the use of a variant call set excluding CH-related variants improved the classification of molecular responders, but had no significant impact on survival.

show abstract

Section: Discussionmentioning

confidence: 99%

Dynamic Changes of Circulating Tumor DNA Predict Clinical Outcome in Patients With Advanced Non–Small-Cell Lung Cancer Treated With Immune Checkpoint Inhibitors

Weber

Leest

Donker

et al. 2021

JCO Precision Oncology

Self Cite

View full text Add to dashboard Cite

show abstract

“…Therefore, researchers have focused on integrating multiple variables and constructing predictive models to more accurately predict the prognosis of patients. Dandachi et al 34 conducted a prospective study using longitudinal tumor fraction trajectories to predict the risk of PFS events in HR + /HER2- ABC patients receiving CDK4 /6i, including those who exhibited resistance to such inhibitors. Through multiple follow-up visits to HR + /HER2- ABC patients and using the Modified Fast Aneuploid Screening Test-SeqS and PCR techniques to evaluate the somatic cell copy numbers of all chromosomes at each follow-up and substituting into the computational model constructed by the researchers to obtain a genome-wide z-score is called a longitudinal z-score, to replace the tumor fraction in the blood.…”

Section: Clinical Prediction Modelmentioning

confidence: 99%

Prognostic Parameters of Palbociclib in HR+/HER2- Advanced Breast Cancer: A Narrative Review

Wang

Chen

et al. 2023

Technol Cancer Res Treat

View full text Add to dashboard Cite

Recent studies have demonstrated that the combination of Cyclin-Dependent Kinase 4/6 Inhibitor (CDK4/6i) and endocrine therapy (ET) is more effective than ET alone and significantly improves progression-free survival (PFS) and overall survival (OS) in patients with hormone receptor-positive (HR+)/human epidermal growth factor receptor-2 negative (HER2-) breast cancer (BC). Palbociclib is the first CDK4/6i approved for use, and its clinical advantages have been shown. However, 30% of patients will continue to develop secondary drug resistance. Therefore, exploring the parameters that can predict the efficacy of Palbociclib and developing a clinical prediction model is essential for evaluating the prognosis of patients.

show abstract

“…In contrast to the studies highlighted above, ctDNA dynamics can be monitored using the combined signal from profiling changes in many mutated genes instead of specific mutations. For instance, a recent study assessed ctDNA levels at baseline and four weeks for 45 patients treated with CDK4/6 inhibitors and endocrine therapy using the 73-gene Guardant360 assay [88] . This work defined a mean variant allele fraction ratio (mVAFR) as an average of mutations found between baseline and week 4 for each patient.…”

Section: Dynamic Ctdna Biomarkers Of Cdk4/6 Inhibitor Efficacy and Re...mentioning

confidence: 99%

“…An additional study evaluated ctDNA using an untargeted sequencing technique, modified Fast Aneuploidy Screening Test-Sequencing System (mFAST-seq) in longitudinal samples from 49 HR+/HER2- metastatic breast cancer patients treated with CDK4/6 inhibitors [ 89 ] . In this work, associations between z-score measurements, which are surrogate measurements to ctDNA fraction, were made to clinical outcomes using joint models, which link data over a protracted period of time and time-to-event.…”

Section: Dynamic Ctdna Biomarkers Of Cdk4/6 Inhibitor Efficacy and Re...mentioning

confidence: 99%

Liquid biopsies to predict CDK4/6 inhibitor efficacy and resistance in breast cancer

Main¹,

Cescon²,

Bratman³

2022

Cancer Drug Resist

View full text Add to dashboard Cite

Cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors combined with endocrine therapy have transformed the treatment of estrogen receptor-positive (ER+) and human epidermal growth factor receptor 2 negative (HER2-) metastatic breast cancer. However, some patients do not respond to this treatment, and patients inevitably develop resistance, such that novel biomarkers are needed to predict primary resistance, monitor treatment response for acquired resistance, and personalize treatment strategies. Circumventing the spatial and temporal limitations of tissue biopsy, newly developed liquid biopsy approaches have the potential to uncover biomarkers that can predict CDK4/6 inhibitor efficacy and resistance in breast cancer patients through a simple blood test. Studies on circulating tumor DNA (ctDNA)-based liquid biopsy biomarkers of CDK4/6 inhibitor resistance have focused primarily on genomic alterations and have failed thus far to identify clear and clinically validated predictive biomarkers, but emerging epigenetic ctDNA methodologies hold promise for further discovery. The present review outlines recent advances and future directions in ctDNA-based biomarkers of CDK4/6 inhibitor treatment response.

show abstract

Longitudinal tumor fraction trajectories predict risk of progression in metastatic HR⁺ breast cancer patients undergoing CDK4/6 treatment

Cited by 12 publications

References 27 publications

Dynamic Changes of Circulating Tumor DNA Predict Clinical Outcome in Patients With Advanced Non–Small-Cell Lung Cancer Treated With Immune Checkpoint Inhibitors

Dynamic Changes of Circulating Tumor DNA Predict Clinical Outcome in Patients With Advanced Non–Small-Cell Lung Cancer Treated With Immune Checkpoint Inhibitors

Prognostic Parameters of Palbociclib in HR+/HER2- Advanced Breast Cancer: A Narrative Review

Liquid biopsies to predict CDK4/6 inhibitor efficacy and resistance in breast cancer

Contact Info

Product

Resources

About

Longitudinal tumor fraction trajectories predict risk of progression in metastatic HR+ breast cancer patients undergoing CDK4/6 treatment

Cited by 12 publications

References 27 publications

Dynamic Changes of Circulating Tumor DNA Predict Clinical Outcome in Patients With Advanced Non–Small-Cell Lung Cancer Treated With Immune Checkpoint Inhibitors

Dynamic Changes of Circulating Tumor DNA Predict Clinical Outcome in Patients With Advanced Non–Small-Cell Lung Cancer Treated With Immune Checkpoint Inhibitors

Prognostic Parameters of Palbociclib in HR+/HER2- Advanced Breast Cancer: A Narrative Review

Liquid biopsies to predict CDK4/6 inhibitor efficacy and resistance in breast cancer

Contact Info

Product

Resources

About

Longitudinal tumor fraction trajectories predict risk of progression in metastatic HR⁺ breast cancer patients undergoing CDK4/6 treatment