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  1. Article: A Comparison of Lenvatinib versus Sorafenib in the First-Line Treatment of Unresectable Hepatocellular Carcinoma: Selection Criteria to Guide Physician's Choice in a New Therapeutic Scenario.

    Dipasquale, Angelo / Marinello, Arianna / Santoro, Armando

    Journal of hepatocellular carcinoma

    2021  Volume 8, Page(s) 241–251

    Abstract: Hepatocellular carcinoma (HCC) is the fifth most common malignancy across the world. Alongside improvement in local approaches for early stages, the prognosis of patients with advanced disease remains poor. The tyrosine kinase inhibitor sorafenib was the ...

    Abstract Hepatocellular carcinoma (HCC) is the fifth most common malignancy across the world. Alongside improvement in local approaches for early stages, the prognosis of patients with advanced disease remains poor. The tyrosine kinase inhibitor sorafenib was the first drug approved for advanced HCC. During the past decade, this has been extensively explored in real-life settings, such as Eastern Cooperative Oncology Group performance status 2, Child-Pugh B liver function, chronic kidney disease, HIV infection, transplant recipients and the elderly. After 10 years, the multikinase inhibitor lenvatinib was approved in first-line setting. The Phase III REFLECT trial established the non-inferiority of lenvatinib compared with sorafenib in terms of overall survival, meanwhile exploratory analysis suggests a potential benefit over sorafenib for patients with HBV chronic infection and positive alpha-fetoprotein value. Experience with lenvatinib for patients not matching the REFLECT trial criteria remains promising but still retrospective. Indeed, the treatment sequence after lenvatinib still remains a crucial issue, considering that standard second-line options were tested only in patients who progressed to sorafenib. Overall, the choice between lenvatinib and sorafenib should take into account key selection criteria from randomized trials, evidence to date in special clinical situations, the physician's experience and patient's preference. Fast approval of atezolizumab plus bevacizumab as first-line treatment for advanced HCC brought an additional element in this scenario. Undoubtedly, lenvatinib and sorafenib remain available options for patients who are not suitable or those progressed to combination immunotherapy. It is conceivable that new systemic options will contribute to design a new treatment algorithm for HCC in the near future. Meanwhile, prospective studies and biomarker analysis are needed to help physicians in the choice between lenvatinib and sorafenib.
    Language English
    Publishing date 2021-04-15
    Publishing country New Zealand
    Document type Journal Article ; Review
    ZDB-ID 2780784-8
    ISSN 2253-5969
    ISSN 2253-5969
    DOI 10.2147/JHC.S270532
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  2. Article ; Online: Prevalence of Thromboembolic Events in Patients With Non-Small Cell Lung Cancer and RET Fusions.

    Aldea, Mihaela / Marinello, Arianna / Guyon, David / Gazzah, Anas / Barlesi, Fabrice / Planchard, David / Besse, Benjamin

    JAMA oncology

    2023  Volume 9, Issue 11, Page(s) 1583–1584

    MeSH term(s) Humans ; Carcinoma, Non-Small-Cell Lung/complications ; Carcinoma, Non-Small-Cell Lung/epidemiology ; Carcinoma, Non-Small-Cell Lung/genetics ; Lung Neoplasms/epidemiology ; Lung Neoplasms/genetics ; Prevalence ; Thromboembolism/epidemiology ; Proto-Oncogene Proteins c-ret/genetics
    Chemical Substances RET protein, human (EC 2.7.10.1) ; Proto-Oncogene Proteins c-ret (EC 2.7.10.1)
    Language English
    Publishing date 2023-09-14
    Publishing country United States
    Document type Journal Article
    ISSN 2374-2445
    ISSN (online) 2374-2445
    DOI 10.1001/jamaoncol.2023.3625
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  3. Article ; Online: Response to first-line pembrolizumab in metastatic

    Rossi, Sabrina / Pagliaro, Arianna / Finocchiaro, Giovanna / Marinello, Arianna / Giordano, Laura / Bria, Emilio / Stefani, Alessio / Vitale, Antonio / Toschi, Luca / D'Argento, Ettore / Santoro, Armando

    Future oncology (London, England)

    2024  Volume 20, Issue 7, Page(s) 373–380

    Abstract: Aims: ...

    Abstract Aims:
    MeSH term(s) Humans ; Carcinoma, Non-Small-Cell Lung/drug therapy ; Carcinoma, Non-Small-Cell Lung/genetics ; Carcinoma, Non-Small-Cell Lung/pathology ; Lung Neoplasms/drug therapy ; Lung Neoplasms/genetics ; Lung Neoplasms/pathology ; Proto-Oncogene Proteins p21(ras)/genetics ; Retrospective Studies ; Antibodies, Monoclonal, Humanized
    Chemical Substances pembrolizumab (DPT0O3T46P) ; Proto-Oncogene Proteins p21(ras) (EC 3.6.5.2) ; KRAS protein, human ; Antibodies, Monoclonal, Humanized
    Language English
    Publishing date 2024-03-06
    Publishing country England
    Document type Journal Article
    ZDB-ID 2274956-1
    ISSN 1744-8301 ; 1479-6694
    ISSN (online) 1744-8301
    ISSN 1479-6694
    DOI 10.2217/fon-2023-0952
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    Zs.A 6478: Show issues Location:
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  4. Article: KRAS in NSCLC: State of the Art and Future Perspectives.

    Cascetta, Priscilla / Marinello, Arianna / Lazzari, Chiara / Gregorc, Vanesa / Planchard, David / Bianco, Roberto / Normanno, Nicola / Morabito, Alessandro

    Cancers

    2022  Volume 14, Issue 21

    Abstract: In NSCLC, KRAS mutations occur in up to 30% of all cases, most frequently at codon 12 and 13. KRAS mutations have been linked to adenocarcinoma histology, positive smoking history, and Caucasian ethnicity, although differences have been described across ... ...

    Abstract In NSCLC, KRAS mutations occur in up to 30% of all cases, most frequently at codon 12 and 13. KRAS mutations have been linked to adenocarcinoma histology, positive smoking history, and Caucasian ethnicity, although differences have been described across KRAS mutational variants subtypes. KRAS mutations often concur with other molecular alterations, notably TP53, STK11, and KEAP1, which could play an important role in treatment efficacy and patient outcomes. For many years, KRAS mutations have been considered undruggable mainly due to a high toxicity profile and low specificity of compounds. Sotorasib and adagrasib are novel KRAS inhibitors that recently gained FDA approval for pre-treated KRAS mutant NSCLC patients, and other molecules such as GDC-6036 are currently being investigated with promising results. Despite their approval, the efficacy of these drugs is lower than expected and progression among responders has been reported. Mechanisms of acquired resistance to anti-KRAS molecules typically involves either on target secondary mutations (e.g., G12, G13, Q61H, R68S, H95, Y96C, V8L) or off-target alterations. Ongoing trials are currently evaluating strategies for implementing efficacy and overcoming acquired resistance to these compounds. Finally, the efficacy of immune-checkpoint inhibitors still needs to be completely assessed and responses to anti-PD-1/PD-L1 agents may strongly depend on concomitant mutations.
    Language English
    Publishing date 2022-11-04
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2527080-1
    ISSN 2072-6694
    ISSN 2072-6694
    DOI 10.3390/cancers14215430
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  5. Article ; Online: Current treatment approaches for brain metastases in

    Rossi, Sabrina / Marinello, Arianna / Pagliaro, Arianna / Franceschini, Davide / Navarria, Pierina / Finocchiaro, Giovanna / Toschi, Luca / Scorsetti, Marta / Santoro, Armando

    Expert review of anticancer therapy

    2022  Volume 23, Issue 1, Page(s) 29–41

    Abstract: Introduction: Oncogene-addicted non-small cell lung cancer (NSCLC) patients present a high incidence of CNS metastases either at diagnosis or during the course of the disease. In this case, patients present with worse prognosis and are often excluded ... ...

    Abstract Introduction: Oncogene-addicted non-small cell lung cancer (NSCLC) patients present a high incidence of CNS metastases either at diagnosis or during the course of the disease. In this case, patients present with worse prognosis and are often excluded from clinical trials unless brain metastases are pre-treated or clinically stable.
    Areas covered: As a result of the discovery of several oncogenic drivers in
    Expert opinion: Last-generation ALK inhibitors have shown slightly superior intracranial activity but pivotal trials do not consider the same endpoints for intracranial efficacy, therefore data are not comparable. Local treatments for BM including surgical resection, stereotactic radiosurgery (SRS) and WBRT, should be integrated with systemic therapies basing on specific criteria like presence of oligoprogression or symptomatic progression.
    MeSH term(s) Humans ; Antineoplastic Agents/therapeutic use ; Brain Neoplasms/secondary ; Carcinoma, Non-Small-Cell Lung/pathology ; Lung Neoplasms/pathology ; Protein-Tyrosine Kinases ; Proto-Oncogene Proteins ; Receptor Protein-Tyrosine Kinases ; Receptor, trkB/metabolism
    Chemical Substances Antineoplastic Agents ; Protein-Tyrosine Kinases (EC 2.7.10.1) ; Proto-Oncogene Proteins ; Receptor Protein-Tyrosine Kinases (EC 2.7.10.1) ; ROS1 protein, human (EC 2.7.10.1) ; Receptor, trkB (EC 2.7.10.1)
    Language English
    Publishing date 2022-12-29
    Publishing country England
    Document type Journal Article
    ZDB-ID 2112544-2
    ISSN 1744-8328 ; 1473-7140
    ISSN (online) 1744-8328
    ISSN 1473-7140
    DOI 10.1080/14737140.2023.2162044
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    Zs.A 5907: Show issues Location:
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  6. Article ; Online: Uncommon single and compound EGFR mutations: clinical outcomes of a heterogeneous subgroup of NSCLC.

    Rossi, Sabrina / Damiano, Paola / Toschi, Luca / Finocchiaro, Giovanna / Giordano, Laura / Marinello, Arianna / Bria, Emilio / D'Argento, Ettore / Santoro, Armando

    Current problems in cancer

    2021  Volume 46, Issue 1, Page(s) 100787

    Abstract: Molecular characterization of non-small-cell lung cancer (NSCLC) is essential to define the correct therapeutic algorithm in metastatic disease. Approximately 90% of epidermal growth factor receptor (EGFR) mutations are usually associated with ... ...

    Abstract Molecular characterization of non-small-cell lung cancer (NSCLC) is essential to define the correct therapeutic algorithm in metastatic disease. Approximately 90% of epidermal growth factor receptor (EGFR) mutations are usually associated with sensitivity to EGFR tyrosine kinase inhibitors (TKIs). The remaining 10% defines a small, extremely heterogeneous subgroup of mutations, with a varied profile of sensitivity and response to target therapies.This retrospective observational study includes 47 patients affected by metastatic NSCLC harboring uncommon EGFR mutations (single or compound mutation). Patients were treated with EGFR-targeting TKIs or platinum-based chemotherapy as first-line treatment.Median OS resulted longer in the compound mutation group when compared to single rare mutations (33.6 vs 12 months; P = 0.473); a similar result was observed for PFS (16 vs 7.6 months; P = 0.281), although statistical significance was not reached. ORR, PFS and OS resulted similar for patients treated with first-line EGFR TKIs or chemotherapy. No difference in terms of PFS and OS was found according to the TKI administered.Compound mutations seem to be a good prognostic indicator for OS; they are also predictive of response to 1st and 2nd generation EGFR TKIs, as well as exon 19 insertions and mutations in codon 719 of exon 18. For mutations in exon 18 (not in codon 719) and exon 20 insertions, chemotherapy seems the most effective available option. The addition of immunotherapy to chemotherapy could change this approach in the next future.
    MeSH term(s) Carcinoma, Non-Small-Cell Lung/drug therapy ; Carcinoma, Non-Small-Cell Lung/genetics ; Carcinoma, Non-Small-Cell Lung/pathology ; ErbB Receptors/genetics ; Humans ; Lung Neoplasms/drug therapy ; Lung Neoplasms/genetics ; Lung Neoplasms/pathology ; Mutation ; Protein Kinase Inhibitors/pharmacology ; Protein Kinase Inhibitors/therapeutic use
    Chemical Substances Protein Kinase Inhibitors ; EGFR protein, human (EC 2.7.10.1) ; ErbB Receptors (EC 2.7.10.1)
    Language English
    Publishing date 2021-08-19
    Publishing country United States
    Document type Journal Article ; Observational Study ; Research Support, Non-U.S. Gov't
    ZDB-ID 441816-5
    ISSN 1535-6345 ; 0147-0272
    ISSN (online) 1535-6345
    ISSN 0147-0272
    DOI 10.1016/j.currproblcancer.2021.100787
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    Se 549: Show issues Location:
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  7. Article: A Case of Pulmonary Sarcoidosis during First-Line Targeted Therapy with Dabrafenib Plus Trametinib in

    Tronconi, Maria Chiara / Marinello, Arianna / Solferino, Alessandra / Grimaudo, Susanna / Ciccarelli, Michele / Manara, Sofia / Cozzaglio, Luca / Mancini, Luca / Borroni, Riccardo / Santoro, Armando

    Case reports in oncology

    2022  Volume 15, Issue 2, Page(s) 560–565

    Abstract: BRAF inhibitors (BRAFi) and MEK inhibitors (MEKi) exert a cytotoxic and immune-mediated effect on metastatic melanoma. The immune-mediated mechanism can lead to some adverse events, including panniculitis, erythema, keratitis, vitiligo-like lesions, or, ... ...

    Abstract BRAF inhibitors (BRAFi) and MEK inhibitors (MEKi) exert a cytotoxic and immune-mediated effect on metastatic melanoma. The immune-mediated mechanism can lead to some adverse events, including panniculitis, erythema, keratitis, vitiligo-like lesions, or, more rarely, sarcoid-like skin reactions. In particular, sarcoidosis-related manifestations during melanoma treatment are characterized mainly by skin involvement and are seldom associated with chest or lymph node lesions. Overall, managing these adverse events can be very challenging from the diagnostic and therapeutic points of view. We present a case of pulmonary sarcoidosis; it is the first without skin involvement and initially only with lung presentation, diagnosed during treatment with BRAFi and MEKi for metastatic cutaneous melanoma. After about 2 years of treatment, with an oncological complete response, a histologically confirmed form of pulmonary sarcoidosis was diagnosed and initially interpreted as tumor progression. Sarcoidosis has always remained asymptomatic. After progression in the thorax and supraclavicular lymph nodes, steroid therapy with prednisone was instituted with total remission of the signs of disease. The targeted therapy has never been interrupted, and the patient still shows a complete response. This clinical case suggests that rare immune-mediated events, such as pulmonary sarcoidosis, should be considered during targeted therapy for metastatic melanoma and not only during treatment with immune checkpoint inhibitors. It also suggests that the interruption of targeted treatment should be accurately considered based on the expected risks or benefits since such immune-mediated events may have low clinical impact.
    Language English
    Publishing date 2022-05-30
    Publishing country Switzerland
    Document type Case Reports
    ZDB-ID 2458961-5
    ISSN 1662-6575
    ISSN 1662-6575
    DOI 10.1159/000524185
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  8. Article ; Online: Clinical predictors of cardiac toxicity in HER2-positive early breast cancer patients treated with adjuvant s.c. versus i.v. trastuzumab.

    De Sanctis, Rita / Giordano, Laura / D'Antonio, Federica / Agostinetto, Elisa / Marinello, Arianna / Guiducci, Daniela / Masci, Giovanna / Losurdo, Agnese / Zuradelli, Monica / Torrisi, Rosalba / Santoro, Armando

    Breast (Edinburgh, Scotland)

    2021  Volume 57, Page(s) 80–85

    Abstract: Background: Few data are available about real-life cardiotoxicity associated with s.c. versus i.v. trastuzumab treatment of early-stage, HER2-positive breast cancer, and little is known about its predisposing factors.: Patients and methods: We ... ...

    Abstract Background: Few data are available about real-life cardiotoxicity associated with s.c. versus i.v. trastuzumab treatment of early-stage, HER2-positive breast cancer, and little is known about its predisposing factors.
    Patients and methods: We retrospectively reviewed data of 363 adult patients treated with adjuvant trastuzumab for HER2-positive breast cancer. Univariate statistical analysis was performed, and a multivariable logistic model was developed to identify independent risk factors of cardiac toxicity.
    Results: Within 5 years, the overall incidence of events meeting our criteria was 11.8%, and an early discontinuation of trastuzumab was recorded in 20 patients (5.5%). No cases of congestive heart failure occurred, neither multiple events per patient were observed. A total of 184 patients received i.v. and 179 received s.c. trastuzumab. Compared with the s.c. formulation, a higher cardiotoxicity rate for the i.v. administration (15.2% vs 8.4%) was found, and particularly in those patients with cardiovascular risk factors (19.3% vs 8.7%), at the univariate and multivariate analyses. Although more patients with prior anthracycline-based chemotherapy experienced cardiac events, the association of this therapy with cardiac events was not significant. The incidence of cardiac events was not influenced by anthropometric data (e.g. body mass index) or a diagnosis of diabetes mellitus. 5-year event-free survival was 91.7% in the overall population; event-free survival rates were similar between the s.c. and the i.v. groups.
    Conclusion: Our study shows a more favorable safety profile of s.c. versus i.v trastuzumab administration. The use of s.c. trastuzumab could be advisable in at-risk patients.
    MeSH term(s) Adult ; Aged ; Aged, 80 and over ; Antibodies, Monoclonal/adverse effects ; Antibodies, Monoclonal/therapeutic use ; Antineoplastic Agents/adverse effects ; Antineoplastic Agents/therapeutic use ; Breast Neoplasms/drug therapy ; Cardiotoxicity/epidemiology ; Chemotherapy, Adjuvant ; Female ; Heart/drug effects ; Humans ; Male ; Middle Aged ; Receptor, ErbB-2/analysis ; Retrospective Studies ; Trastuzumab/adverse effects ; Trastuzumab/therapeutic use ; Ventricular Function, Left/drug effects
    Chemical Substances Antibodies, Monoclonal ; Antineoplastic Agents ; ERBB2 protein, human (EC 2.7.10.1) ; Receptor, ErbB-2 (EC 2.7.10.1) ; Trastuzumab (P188ANX8CK)
    Language English
    Publishing date 2021-03-17
    Publishing country Netherlands
    Document type Journal Article
    ZDB-ID 1143210-x
    ISSN 1532-3080 ; 0960-9776
    ISSN (online) 1532-3080
    ISSN 0960-9776
    DOI 10.1016/j.breast.2021.03.004
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    Zs.A 3620: Show issues Location:
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  9. Article ; Online: Liquid Biopsies for Circulating Tumor DNA Detection May Reveal Occult Hematologic Malignancies in Patients With Solid Tumors.

    Aldea, Mihaela / Tagliamento, Marco / Bayle, Arnaud / Vasseur, Damien / Vergé, Véronique / Marinello, Arianna / Danlos, François-Xavier / Blanc-Durand, Felix / Bernard, Elsa / Cerbone, Luigi / Mosele, Maria Fernanda / Renneville, Aline / Hadoux, Julien / Loriot, Yohann / Sakkal, Madona / Vozy, Aurore / Sarkozy, Clementine / Smolenschi, Cristina / Nicotra, Claudio /
    Martin-Romano, Patricia / Boccon-Gibod, Clementine / Habza, Wafikaamira / Lazarovici, Julien / Ponce, Santiago / Hollebecque, Antoine / Marzac, Christophe / Lacroix, Ludovic / Barlesi, Fabrice / André, Fabrice / Besse, Benjamin / Rouleau, Etienne / Italiano, Antoine / Micol, Jean-Baptiste

    JCO precision oncology

    2023  Volume 7, Page(s) e2200583

    Abstract: Purpose: High-risk clonal hematopoiesis (CH) is frequently incidentally found in patients with solid tumors undergoing plasma cell-free DNA sequencing. Here, we aimed to determine if the incidental detection of high-risk CH by liquid biopsy may reveal ... ...

    Abstract Purpose: High-risk clonal hematopoiesis (CH) is frequently incidentally found in patients with solid tumors undergoing plasma cell-free DNA sequencing. Here, we aimed to determine if the incidental detection of high-risk CH by liquid biopsy may reveal occult hematologic malignancies in patients with solid tumors.
    Materials and methods: Adult patients with advanced solid cancers enrolled in the Gustave Roussy Cancer Profiling study (ClinicalTrials.gov identifier: NCT04932525) underwent at least one liquid biopsy (FoundationOne Liquid CDx). Molecular reports were discussed within the Gustave Roussy Molecular Tumor Board (MTB). Potential CH alterations were observed, and patients referred to hematology consultation in the case of pathogenic mutations in
    Results: Between March and October 2021, 1,416 patients were included. One hundred ten patients (7.7%) carried at least one high-risk CH mutation:
    Conclusion: The incidental findings of high-risk CH through liquid biopsy may trigger diagnostic hematologic tests and reveal an occult hematologic malignancy. Patients should have a multidisciplinary case-by-case evaluation.
    MeSH term(s) Adult ; Humans ; Circulating Tumor DNA/genetics ; Splicing Factor U2AF ; Hematologic Neoplasms/genetics ; Neoplasms, Unknown Primary ; Transcription Factors ; Liquid Biopsy ; Hematology
    Chemical Substances Circulating Tumor DNA ; Splicing Factor U2AF ; Transcription Factors
    Language English
    Publishing date 2023-01-17
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ISSN 2473-4284
    ISSN (online) 2473-4284
    DOI 10.1200/PO.22.00583
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  10. Article ; Online: Eribulin across multiple lines of chemotherapy: a retrospective study on quality of life and efficacy in metastatic breast cancer patients.

    Quaquarini, Erica / Sottotetti, Federico / D'Ambrosio, Daniela / Malovini, Alberto / Morganti, Stefania / Marinello, Arianna / Pavesi, Lorenzo / Frascaroli, Mara

    Future oncology (London, England)

    2017  Volume 13, Issue 11s, Page(s) 11–23

    Abstract: This study evaluates efficacy, tolerability and health-related quality of life of eribulin in patients with metastatic breast cancer. Predictive and/or prognostic factors of outcome were also analyzed. Among 44 women receiving eribulin mesylate, one ... ...

    Abstract This study evaluates efficacy, tolerability and health-related quality of life of eribulin in patients with metastatic breast cancer. Predictive and/or prognostic factors of outcome were also analyzed. Among 44 women receiving eribulin mesylate, one patient had a complete response, 22.7% a partial response and 25% a stable disease. Median overall survival and median progression-free survival were 11.8 and 4.5 months, respectively. Treatment was well tolerated; the most frequent adverse events were neutropenia (52%), leukopenia (50%), fatigue (38%) and alopecia (40%). No significant reductions of health-related quality of life parameters were observed. Disease control during previous chemotherapy lines was related with better outcome with eribulin. In conclusion, eribulin treatment should be considered in a multiple chemotherapy lines strategy in metastatic breast cancer.
    MeSH term(s) Adult ; Aged ; Antineoplastic Agents/administration & dosage ; Antineoplastic Agents/adverse effects ; Antineoplastic Agents/therapeutic use ; Antineoplastic Combined Chemotherapy Protocols/adverse effects ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Biomarkers, Tumor ; Breast Neoplasms/diagnosis ; Breast Neoplasms/drug therapy ; Breast Neoplasms/mortality ; Female ; Furans/administration & dosage ; Furans/adverse effects ; Furans/therapeutic use ; Humans ; Kaplan-Meier Estimate ; Ketones/administration & dosage ; Ketones/adverse effects ; Ketones/therapeutic use ; Middle Aged ; Neoplasm Metastasis ; Quality of Life ; Retreatment ; Retrospective Studies ; Treatment Outcome
    Chemical Substances Antineoplastic Agents ; Biomarkers, Tumor ; Furans ; Ketones ; eribulin (LR24G6354G)
    Language English
    Publishing date 2017-04
    Publishing country England
    Document type Journal Article
    ZDB-ID 2184533-5
    ISSN 1744-8301 ; 1479-6694
    ISSN (online) 1744-8301
    ISSN 1479-6694
    DOI 10.2217/fon-2016-0517
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