Davide Ciardiello

European Institute of Oncology

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Co-Authors

Teresa Troiani

University of Campania "Luigi Vanvitelli"

115

Giulia Martini

University of Campania "Luigi Vanvitelli"

113

Stefania Napolitano

University of Campania "Luigi Vanvitelli"

108

Fortunato Ciardiello

University of Campania "Luigi Vanvitelli"

Erika Martinelli

University of Campania "Luigi Vanvitelli"

Pietro Paolo Vitiello

IFOM

Floriana Morgillo

University of Campania "Luigi Vanvitelli"

Claudia Cardone

Istituto Nazionale Tumori IRCCS "Fondazione G. Pascale"

Vincenzo De Falco

University of Campania "Luigi Vanvitelli"

Erika Martinelli

University of Campania "Luigi Vanvitelli"

Cooperative Institutions

University of Campania "Luigi Vanvitelli"

160

Istituti di Ricovero e Cura a Carattere Scientifico

158

University of Naples Federico II

122

European Institute of Oncology

University of Milan

Casa Sollievo della Sofferenza

Vall d'Hebron Institute of Oncology

Istituto Nazionale Tumori IRCCS "Fondazione G. Pascale"

Azienda Ospedaliera Universitaria Università degli Studi della Campania Luigi Vanvitelli

Vall d'Hebron Hospital Universitari

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Promising targetable biomarkers in pancreatic neuroendocrine tumours

Expert Review of Endocrinology & Metabolism (2023)

Michele Borghesani Lorenzo Gervaso C.A. Cella L. Benini Davide Ciardiello

Introduction In the treatment scenario of PanNETs-targeted therapies are desired but limited, as rarity and heterogeneity on PanNETs pose limitations to their development.

Druggability

Drug Development

Targeted Therapy

Biomarker Discovery

Grading (engineering)

10.1080/17446651.2023.2248239

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Citations (0)

Multi-Omic Approaches in Colorectal Cancer beyond Genomic Data

Journal of Personalized Medicine (2022)

Emilia Sardo Stefania Napolitano Carminia Maria Della Corte Davide Ciardiello Antonio Raucci

Colorectal cancer (CRC) is one of the most frequent tumours and one of the major causes of morbidity and mortality globally. Its incidence has increased in recent years and could be linked to unhealthy dietary habits combined with environmental and hereditary factors, which can lead to genetic and epigenetic changes and induce tumour development. The model of CRC progression has always been based on a genomic, parametric, static and complex approach involving oncogenes and tumour suppressor genes. Recent advances in omics sciences have sought a paradigm shift to a multiparametric, immunological-stromal, and dynamic approach for a better understanding of carcinogenesis and tumour heterogeneity. In the present paper, we review the most important preclinical and clinical data and present recent discoveries in the field of transcriptomics, proteomics, metagenomics and radiomics in CRC disease.

Omics

10.3390/jpm12020128

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Citations (11)

Anti-tumor Activity of Cetuximab Plus Avelumab in Non-Small Cell Lung Cancer Patients Involves Innate Immunity Activation: Findings from the CAVE-Lung Trial

Research Square (Research Square) (2022)

Carminia Maria Della Corte Morena Fasano Vincenza Ciaramella Flora Cimmino Robert J. Cardnell

Abstract Background: We recently conducted Cetuximab-AVElumab-Lung (CAVE-Lung), a proof-of-concept, translational and clinical trial, to evaluate the combination of two IgG1 monoclonal antibodies (mAb): avelumab, an anti-PD-L1 drug, and cetuximab, an anti-epidermal growth factor receptor (EGFR) drug, as second- or third-line treatment in non-small cell lung cancer (NSCLC) patients. We have reported clinically relevant anti-tumor activity in 6/16 patients. Clinical benefit was accompanied by Natural Killer (NK) cell-mediated antibody-dependent cell cytotoxicity (ADCC). Among the 6 responding patients, 3 had progressed after initial response to a previous treatment with single agent anti-PD-1, nivolumab or pembrolizumab. Methods: We report long-term clinical follow-up and additional findings on the anti-tumor activity and on the immune effects of cetuximab plus avelumab treatment for these 3 patients. Results: As of November 30, 2021, 2/3 patients were alive. One patient was still on treatment from 34 months, while the other two patients had progression free survival (PFS) of 15 and 19 months, respectively. Analysis of serially collected peripheral blood mononuclear cells (PBMC) revealed long-term activation of NK cell-mediated ADCC. Comprehensive genomic profile analysis found somatic mutations and germline rare variants in DNA damage response (DDR) genes. Furthermore, by transcriptomic analysis of The Cancer Genome Atlas (TCGA) dataset we found that DDR mutant NSCLC displayed high STING pathway gene expression. In NSCLC patient-derived three-dimensional in vitro spheroid cultures, cetuximab plus avelumab treatment induced additive cancer cell growth inhibition as compared to single agent treatment. This effect was partially blocked by treatment with an anti-CD16 mAb, suggesting a direct involvement of NK cell activation. Furthermore, cetuximab plus avelumab treatment induced 10-, 20-, and 20-fold increase, respectively, in the gene expression of CCL5 and CXCL10 , two STING downstream effector cytokines, and of interferon β , as compared to untreated control samples. Conclusions: DDR mutations may contribute to DDR-induced STING pathway with sustained innate immunity activation following cetuximab plus avelumab combination in previously treated, PD-1 inhibitor responsive NSCLC patients.

Avelumab

10.21203/rs.3.rs-1254137/v1

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Supplementary Figure Legends from Primary and Acquired Resistance of Colorectal Cancer Cells to Anti-EGFR Antibodies Converge on MEK/ERK Pathway Activation and Can Be Overcome by Combined MEK/EGFR Inhibition

Teresa Troiani Stefania Napolitano Donata Vitagliano Floriana Morgillo Anna Capasso

10.1158/1078-0432.22446587.v1

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BRAFV600E mutant metastatic colorectal cancer: Current advances in personalized treatment and future perspectives

Cancer Treatment Reviews (2025)

Stefania Napolitano Davide Ciardiello Eleonora Cioli Erika Martinelli Teresa Troiani

10.1016/j.ctrv.2025.102905

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P-96 Circulating tumor-derived DNA (ctDNA) clearance in patients with locally advanced rectal cancer treated with multimodal treatment

Annals of Oncology (2023)

Lorenzo Gervaso Davide Ciardiello Liliana Ascione Laura Boldrini Lorenzo Guidi

Liquid biopsy

Concomitant

Clinical endpoint

10.1016/j.annonc.2023.04.152

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Cutaneous Metastasis from Colorectal Cancer: Making Light on an Unusual and Misdiagnosed Event

Life (2021)

Paola Parente Davide Ciardiello Luca Reggiani Bonetti Vincenzo Famiglietti Gerardo Cazzato

Cutaneous metastasis from solid tumors is a rare event and usually represents a late occurrence in the natural history of an advanced visceral malignancy. Rarely, cutaneous metastasis has been described in colorectal cancer patients. The most frequent cutaneous site of colorectal metastasis is the surgical scar in the abdomen following the removal of the primary malignancy, followed by the extremities, perineum, head, neck, and penis. Metastases to the thigh and back of the trunk are anecdotical. Dermatological diagnosis of cutaneous metastasis can be quite complex, especially in unusual sites, such as in the facial skin or thorax and in cases of single cutaneous lesions since metastasis from colorectal cancer is not usually the first clinical hypothesis, leading to misdiagnosis. To date, due to the rarity of cutaneous metastasis from colorectal cancer, little evidence, most of which is based on case reports and very small case series, is currently available. Therefore, a better understanding of the clinic-pathological characteristics of this unusual metastatic site represents an unmet clinical need. We present a large series of 29 cutaneous metastases from colorectal cancer with particular concerns regarding anatomic localization and the time of onset with respect to primitive colorectal cancer and visceral metastases.

10.3390/life11090954

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Citations (8)

Cetuximab Rechallenge Plus Avelumab in Pretreated Patients With RAS Wild-type Metastatic Colorectal Cancer

JAMA Oncology (2021)

Erika Martinelli Giulia Martini Vincenzo Famiglietti Teresa Troiani Stefania Napolitano

Rechallenge therapy with anti-epidermal growth factor receptor (EGFR) drugs has been suggested in patients with chemo-refractory RAS wild-type (WT) metastatic colorectal cancer (mCRC) after initial response to anti-EGFR-based first-line treatment. The association of treatment with cetuximab plus avelumab with overall survival (OS) may be worthy of investigation in this setting.To assess the efficacy and safety of cetuximab rechallenge therapy plus avelumab.This single-arm, multicenter phase 2 trial enrolled patients from August 2018 to February 2020. Eligible patients with RAS WT mCRC had a complete or partial response to first-line chemotherapy plus anti-EGFR drugs, developed acquired resistance, and failed second-line therapy. Baseline circulating tumor DNA (ctDNA) for KRAS, NRAS, BRAF, and EGFR-S492R mutation analysis was done.Patients received avelumab (10 mg/kg every 2 weeks) and cetuximab (400 mg/m2 and, subsequently, 250 mg/m2 weekly) until disease progression or unacceptable toxic effects.The primary end point was OS. Secondary end points were progression-free survival (PFS), overall response rate (ORR), and safety.Seventy-seven patients were enrolled (42 men, 35 women; median age, 63 years); 71 had microsatellite stable tumors (MSS), 3 microsatellite instability-high tumors (MSI-H), 3 unknown. The study met the primary end point, with median OS (mOS) of 11.6 months (95% CI, 8.4-14.8 months). Median PFS (mPFS) was 3.6 months (95% CI, 3.2-4.1 months). Common grade-3 adverse events were cutaneous eruption, 11 (14%), and diarrhea, 3 (4%). For 67 of 77 (87%) patients, baseline analysis of plasma circulating tumor DNA (ctDNA) for KRAS, NRAS, BRAF, and EGFR-S492R variations was feasible. Forty-eight patients had WT disease, whereas 19 had mutations. Patients with RAS/BRAF WT ctDNA had mOS of 17.3 months (95% CI, 12.5-22.0 months) compared with 10.4 months (95% CI, 7.2-13.6 months) in patients with mutated ctDNA (hazard ratio [HR], 0.49; 95% CI, 0.27-0.90; P = .02). The mPFS was 4.1 months (95% CI, 2.9-5.2 months) in RAS/BRAF WT patients compared with 3.0 months (95% CI, 2.6-3.5 months) in patients with mutated ctDNA (HR, 0.42; 95% CI, 0.23-0.75; P = .004).The findings of this single-arm phase 2 trial suggest that cetuximab plus avelumab is an active, well tolerated rechallenge therapy in RAS WT mCRC. Plasma ctDNA analysis before treatment may allow selection of patients who could benefit.ClinicalTrials.gov Identifier: NCT04561336.

Clinical endpoint

Microsatellite Instability

Panitumumab

Progression-free survival

Avelumab

10.1001/jamaoncol.2021.2915

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Citations (119)

BRAF, MEK and EGFR inhibition as treatment strategies in BRAF V600E metastatic colorectal cancer

Therapeutic Advances in Medical Oncology (2021)

Javier Ros Iosune Baraibar Emilia Sardo Nuria Mulet Francesc Salvà

Introduction: BRAF driver mutations are found in up to 15% of patients with colorectal cancer (CRC) and lead to constitutive activation of BRAF kinase and sustained RAS/RAF/MEK/ERK pathway signaling. BRAF mutations define a sub-population characterized by a poor prognosis and dismal median survival. Following successful outcomes with BRAF inhibition in BRAF mutant metastatic melanoma, this approach was evaluated in metastatic colorectal cancer (mCRC). The development and combination of targeted therapies against multiple signaling pathways has proved particularly successful, with improved survival and response rates. Areas covered: This review addresses the development of therapeutic strategies with inhibitors targeting MAPK/ERK and EGFR signaling in BRAF V600E mutated mCRC, focusing on encorafenib, binimetinib and cetuximab. A pharmacological and clinical review of these drugs and the therapeutic approaches behind their optimization are presented. Expert opinion: Exploiting knowledge of the mechanisms of resistance to BRAF inhibitors has been crucial to developing effective therapeutic strategies in BRAF-V600E mutant mCRC. The BEACON trial is a successful example of this approach, using encorafenib and cetuximab with or without binimetinib in patients with previously treated BRAF V600E mutant mCRC, showing an impressive improvement in clinical outcomes and tolerable toxicity compared with chemotherapy, establishing a new standard of care in this setting.

V600E

Targeted Therapy

10.1177/1758835921992974

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Citations (45)

Exploring biological heterogeneity and implications on novel treatment paradigm in BRAF-mutant metastatic colorectal cancer

Critical Reviews in Oncology/Hematology (2022)

Maria Grazia Rodriquenz Davide Ciardiello Tiziana Pia Latiano Brigida Anna Maiorano Erika Martinelli

Targeted Therapy

10.1016/j.critrevonc.2022.103657

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Citations (8)