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Radiomic predicts early response to CDK4/6 inhibitors in hormone receptor positive metastatic breast cancer.

ABSTRACT: The combination of Cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) and endocrine therapy (ET) is the standard of care for hormone receptor-positive (HR + ), human epidermal growth factor receptor 2-negative (HER2-) metastatic breast cancer (MBC). Currently, there are no robust biomarkers that can predict response to CDK4/6i, and it is not clear which patients benefit from this therapy. Since MBC patients with liver metastases have a poorer prognosis, developing predictive biomarkers that could identify patients likely to respond to CDK4/6i is clinically important. Here we show the ability of imaging texture biomarkers before and a few cycles after CDK4/6i therapy, to predict early response and overall survival (OS) on 73 MBC patients with known liver metastases who received palbociclib plus ET from two sites. The delta radiomic model was associated with OS in validation set (HR: 2.4; 95% CI, 1.06-5.6; P = 0.035; C-index = 0.77). Compared to RECIST response, delta radiomic features predicted response with area under the curve (AUC) = 0.72, 95% confidence interval (CI) 0.67-0.88. Our study revealed that radiomics features can predict a lack of response earlier than standard anatomic/RECIST 1.1 assessment and warrants further study and clinical validation.

SUBMITTER: Khorrami M

PROVIDER: S-EPMC10421862 | biostudies-literature | 2023 Aug

REPOSITORIES: biostudies-literature

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Radiomic predicts early response to CDK4/6 inhibitors in hormone receptor positive metastatic breast cancer.

Khorrami Mohammadhadi M Viswanathan Vidya Sakar VS Reddy Priyanka P Braman Nathaniel N Kunte Siddharth S Gupta Amit A Abraham Jame J Montero Alberto J AJ Madabhushi Anant A

NPJ breast cancer 20230811 1

The combination of Cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) and endocrine therapy (ET) is the standard of care for hormone receptor-positive (HR + ), human epidermal growth factor receptor 2-negative (HER2-) metastatic breast cancer (MBC). Currently, there are no robust biomarkers that can predict response to CDK4/6i, and it is not clear which patients benefit from this therapy. Since MBC patients with liver metastases have a poorer prognosis, developing predictive biomarkers that could ...[more]

PMID: 37567880

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Project description:ImportanceEndocrine therapy (ET) combined with cyclin-dependent kinase 4/6 inhibitor (CDK4/6i) agents is the standard first-line treatment for patients with hormone receptor-positive, ERBB2 (formerly HER2 or HER2/neu)-negative metastatic breast cancer. However, optimal therapy after tumor progression to ET plus CDK4/6i remains unclear.ObjectiveTo evaluate progression-free survival (PFS) and overall survival (OS) in the clinical practice setting in patients with hormone receptor-positive, ERBB2-negative metastatic breast cancer following progression with ET plus CDK4/6i.Design, setting, and participantsThe multicenter retrospective cohort study included 506 patients diagnosed with hormone receptor-positive, ERBB2-negative metastatic breast cancer between April 22, 2015, and January 31, 2023, and who received ET-based or chemotherapy (CT)-based treatment following progression during ET plus CDK4/6i. Outcomes were analyzed based on treatment type, clinicopathologic features, and the duration of prior CDK4/6i therapy.Main outcomes and measuresThe primary end point was PFS in the clinical practice setting, defined as the time between the initiation of the first systemic treatment on tumor progression to ET plus CDK4/6i treatment and the detection of disease progression or patient death from any cause. The secondary end point was OS in the clinical practice setting, defined as the time interval between tumor progression during ET plus CDK4/6i treatment and patient death from any cause.ResultsIn 506 women (median age at diagnosis, 52.4 [IQR, 44.6-62.8] years) diagnosed with hormone receptor-positive, ERBB2-negative metastatic breast cancer progressing during ET plus CDK4/6i, independent factors associated with poorer PFS outcomes were visceral metastases (hazard ratio [HR], 1.45; 95% CI, 1.17-1.80; P = .008) and de novo metastatic disease (HR, 1.25; 95% CI, 1.01-1.54; P = .04). A longer duration of CDK4/6i therapy (OS HR, 0.55; 95% CI, 0.41-0.73; P < .001) and an older age (PFS HR, 0.99; 95% CI 0.98-1.00; P = .03) were associated with better outcomes. Compared with oral CT, both intravenous CT- and ET-based treatments were associated with shorter PFS (intravenous CT: hazard ratio [HR], 1.45; 95% CI, 1.11-1.89; P = .006; everolimus plus exemestane: HR, 1.38; 95% CI, 1.06-1.78; P = .02; ET only: HR, 1.38; 95% CI, 1.05-1.89; P = .02). A duration of CDK4/6i treatment exceeding 12 months was associated with longer OS (HR, 0.55; 95% CI, 0.41-0.73; P < .001). Among patients with visceral metastases, intravenous CT was associated with shorter OS compared with oral CT (HR, 1.52; 95% CI, 1.03-2.24; P = .04).Conclusions and relevanceIn this cohort study, the duration of tumor control achieved with CDK4/6i-based therapy and the presence of visceral metastases emerged as key factors that may affect treatment decision. Oral CT may offer potential benefits for specific patient subgroups.

Project description:BackgroundThe combination of cyclin-dependent kinases 4/6 inhibitors (CDK4/6is) and endocrine therapy (ET) is standard of care for patients with hormone receptor-positive (HR+), HER2-negative (HER2-) advanced breast cancer (BC). However, studies evaluating adjuvant CDK4/6is provided contradictory results thus far.Materials and methodsWe conducted a systematic review and meta-analysis to assess if the addition of CDK4/6is to adjuvant ET impacts on survival's outcomes and safety of patients with HR+/HER2- early BC (EBC). This study was conducted according to Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) guidelines and was registered in the PROSPERO database (ID: CRD42020218597). A systematic review of PubMed, Cochrane and EMBASE databases and major conference proceedings was performed up to 15 December 2020. All randomized controlled trials including patients with HR+/HER2- EBC treated with CDK4/6is plus ET versus ET alone in the adjuvant setting were included. Pooled hazard ratios (HRs) and odds ratios (ORs) for survival and safety outcomes, respectively, were calculated with 95% confidence intervals (95% CIs) using random effect models.ResultsWith data available from three studies (N = 12 647), the addition of CDK4/6is to adjuvant ET showed a trend for a benefit in terms of invasive disease-free survival (IDFS; HR 0.85, 95% CI 0.71-1.01; P = 0.071). No significant improvement in distant relapse-free survival was observed (HR 0.83, 95% CI 0.58-1.19; P = 0.311). The risk of all-grade toxicities and early treatment discontinuation increased significantly with the addition of CDK4/6is to ET (OR 9.36, 95% CI 3.46-25.33, P < 0.001, and OR 22.11, 95% CI 9.45-51.69, P < 0.001, respectively).ConclusionThe administration of adjuvant CDK4/6is to patients with HR+/HER2- EBC showed a trend for an IDFS benefit and an increase in the risk of toxicities and treatment discontinuation. The role of adjuvant CDK4/6is remains controversial and a longer follow-up of these randomized controlled trials is needed before supporting a straightforward change in clinical practice.

Dataset Information

Radiomic predicts early response to CDK4/6 inhibitors in hormone receptor positive metastatic breast cancer.

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Radiomic predicts early response to CDK4/6 inhibitors in hormone receptor positive metastatic breast cancer.

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