Response evaluation with 18F-FDG PET/CT in metastatic breast cancer patients treated with Palbociclib: first experience in clinical practice

Taralli, Silvia; Lorusso, Margherita; Scolozzi, Valentina; Masiello, Valeria; Marazzi, Fabio; Calcagni, Maria Lucia

doi:10.1007/s12149-018-01323-8

Cited by 21 publications

(14 citation statements)

References 18 publications

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“…A recent study by Taralli et al [23] employed FDG-PET to assess the response of breast cancer patients to CDK4/6 inhibitor therapy. In contrast to the present study, Taralli et al [23] did not investigate early treatment changes as the interval CDK4/6 inhibitor treatment start and follow-up PET was 143 days (median), whereas the interval between baseline and the follow-up PET after the start of CDK4/6 inhibitor was 14 days (median) in our study. Therefore, we were able to assess the very early metabolic response to therapy, which offers the chance of early treatment optimization.…”

Section: Discussionmentioning

confidence: 99%

[18F]-Fluorodeoxyglucose Positron Emission Tomography/CT to Assess the Early Metabolic Response in Patients with Hormone Receptor-Positive HER2-Negative Metastasized Breast Cancer Treated with Cyclin-Dependent 4/6 Kinase Inhibitors

et al. 2021

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Introduction: Addition of cyclin-dependent 4/6 kinase (CDK4/6) inhibitors to endocrine therapy is standard of care in the treatment of women with advanced hormone receptor-positive HER2-negative breast cancer. However, the predictive factors for the treatment response to CDK4/6 inhibitor therapy are poorly elucidated. Early changes in the by [18F]-fluorodeoxyglucose positron emission tomography (FDG-PET) uptake of tumors receiving different kinds of therapy have proven to reliably predict treatment outcomes in a variety of malignancies. Therefore, the feasibility of early metabolic response assessment to predict the long-term treatment response to CDK4/6 inhibitor therapy was evaluated in the present study. Methods: Eight patients underwent FDG-PET/CT before and after the initiation of CDK4/6 inhibitor therapy (ribociclib, palbociclib or abemcaciclib). CDK4/6 inhibitor therapy was combined with either aromatase inhibition or fulvestrant. The median interval between the treatment start (including baseline PET) and the follow-up PET examination was 14 days. Conventional radiographic staging was performed 3 months after the start of CDK4/6 inhibitor therapy. The percentual changes in molecular tumor volume, SUVpeak, the summed SUVpeak of up to 5 metastases (PERCIST-5), and total lesion glycolysis (TLG) were calculated for each patient. Results: Three patients showed progressive disease after 3 months of CDK4/6 inhibitor therapy, whereas 5 patients showed disease control (3 stable disease and 2 partial remission). Disease control was maintained in these patients (follow-up range 7–22 months). Patients with disease control had a significantly greater decline in TLG (–55.3 vs. 16.7%; p < 0.05). The same was true for the PERCIST-5 (–21.9 vs. 11.3%, p < 0.05). All patients with progressive TLG showed treatment failure and/or a poor outcome. Conclusion: Elevated TLG on early FDG-PET seems to be associated with long-term treatment failure and a poor outcome in patients undergoing CDK4/6 inhibitor therapy for metastatic breast cancer. Early findings indicate a potential prognostic value of early FDG-PET in this setting and warrant a prospective evaluation.

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Section: Discussionmentioning

confidence: 99%

[18F]-Fluorodeoxyglucose Positron Emission Tomography/CT to Assess the Early Metabolic Response in Patients with Hormone Receptor-Positive HER2-Negative Metastasized Breast Cancer Treated with Cyclin-Dependent 4/6 Kinase Inhibitors

et al. 2021

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“…The impact of palbociclib/paclitaxel combinations on glucose metabolism may be relevant in the clinic, considering that 18 F-FDG PET/CT, largely used for both cancer staging and assessment of response to chemotherapy, has recently emerged as an useful tool for monitoring the response to palbociclib in ER-positive and HER2-negative metastatic BC patients, especially to select the patients with no clinical benefit 34 .…”

Section: Discussionmentioning

confidence: 99%

Pre-treatment with the CDK4/6 inhibitor palbociclib improves the efficacy of paclitaxel in TNBC cells

Cretella

Fumarola

Bonelli

et al. 2019

Sci Rep

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Triple Negative Breast Cancer (TNBC) is a challenging disease due to the lack of druggable targets; therefore, chemotherapy remains the standard of care and the identification of new targets is a high clinical priority. Alterations in the components of the cell cycle machinery have been frequently reported in cancer; given the success obtained with the CDK4/6 inhibitor palbocicib in ER-positive BC, we explored the potential of combining this drug with chemotherapy in Rb-positive TNBC cell models. The simultaneous combination of palbociclib with paclitaxel exerted an antagonistic effect; by contrast, the sequential treatment inhibited cell proliferation and increased cell death more efficaciously than single treatments. By down-regulating the E2F target c-myc, palbociclib reduced HIF-1α and GLUT-1 expression, and hence glucose uptake and consumption both under normoxic and hypoxic conditions. Importantly, these inhibitory effects on glucose metabolism were enhanced by palbociclib/paclitaxel sequential combination; the superior efficacy of such combination was ascribed to the ability of paclitaxel to inhibit palbociclib-mediated induction of AKT and to further down-regulate the Rb/E2F/c-myc signaling. Our results suggest that the efficacy of standard chemotherapy can be significantly improved by a pre-treatment with palbociclib, thus offering a better therapeutic option for Rb-proficient TNBC.

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“… 12 Compared with Standard Response Evaluation (SRE, based on clinico-laboratory and morphological data), Metabolic Response Evaluation (MRE, based on PET/CT) increased the proportion of patients classified with progressive disease from 25% to 50% and differed from SRE in 8/12 patients: 3/8 shifted from stable disease or undetermined response to metabolic progression (more unfavorable category), 4/8 from stable disease to partial or complete metabolic response, and 1/8 from partial response to complete metabolic response (more favorable category). 203 PMID: 30569442 PET 18 F-FES 18 F-FDG Letrozole combined with CDK inhibition ER and CDK4/6 Metastatic ER-positive and HER2-negative BC patients. 30 Median time to progression (TTP) was 73 weeks [95% confidence interval (CI) 21 to ∞] in 7 patients with 100% FES-positive disease, 27 weeks (14–49) in heterogeneous FES-positive disease (20 patients), and 15 weeks (9 to ∞) without FES positivity (three patients; log-rank P = 0.30).…”

Section: Application Of Molecular Imaging In Targeted Therapymentioning

confidence: 99%

Molecular and functional imaging in cancer-targeted therapy: current applications and future directions

Bai

Qiu

Zhang

2023

Sig Transduct Target Ther

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Targeted anticancer drugs block cancer cell growth by interfering with specific signaling pathways vital to carcinogenesis and tumor growth rather than harming all rapidly dividing cells as in cytotoxic chemotherapy. The Response Evaluation Criteria in Solid Tumor (RECIST) system has been used to assess tumor response to therapy via changes in the size of target lesions as measured by calipers, conventional anatomically based imaging modalities such as computed tomography (CT), and magnetic resonance imaging (MRI), and other imaging methods. However, RECIST is sometimes inaccurate in assessing the efficacy of targeted therapy drugs because of the poor correlation between tumor size and treatment-induced tumor necrosis or shrinkage. This approach might also result in delayed identification of response when the therapy does confer a reduction in tumor size. Innovative molecular imaging techniques have rapidly gained importance in the dawning era of targeted therapy as they can visualize, characterize, and quantify biological processes at the cellular, subcellular, or even molecular level rather than at the anatomical level. This review summarizes different targeted cell signaling pathways, various molecular imaging techniques, and developed probes. Moreover, the application of molecular imaging for evaluating treatment response and related clinical outcome is also systematically outlined. In the future, more attention should be paid to promoting the clinical translation of molecular imaging in evaluating the sensitivity to targeted therapy with biocompatible probes. In particular, multimodal imaging technologies incorporating advanced artificial intelligence should be developed to comprehensively and accurately assess cancer-targeted therapy, in addition to RECIST-based methods.

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Response evaluation with 18F-FDG PET/CT in metastatic breast cancer patients treated with Palbociclib: first experience in clinical practice

Cited by 21 publications

References 18 publications

[18F]-Fluorodeoxyglucose Positron Emission Tomography/CT to Assess the Early Metabolic Response in Patients with Hormone Receptor-Positive HER2-Negative Metastasized Breast Cancer Treated with Cyclin-Dependent 4/6 Kinase Inhibitors

[18F]-Fluorodeoxyglucose Positron Emission Tomography/CT to Assess the Early Metabolic Response in Patients with Hormone Receptor-Positive HER2-Negative Metastasized Breast Cancer Treated with Cyclin-Dependent 4/6 Kinase Inhibitors

Pre-treatment with the CDK4/6 inhibitor palbociclib improves the efficacy of paclitaxel in TNBC cells

Molecular and functional imaging in cancer-targeted therapy: current applications and future directions

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