المؤلفون: Li, Y, Yu, Z, Schenk, M, Lagovsky, I, Illig, D, Walz, C, Rohlfs, M, Conca, R, Muise, AM, Snapper, SB, Uhlig, HH, Zion Garty, B, Klein, C, Kotlarz, D

الوصف: Background: Toll-like receptors (TLRs) are important pattern recognition receptors that sense microbes and control host defense. Myeloid differentiation protein 2 (MD2) is the indispensable coreceptor for TLR4, facilitating the binding to the gram-negative bacterial cell wall component LPS and activation of downstream signaling. Objective: We sought to provide phenotypic and mechanistic insights into human MD2 deficiency. Methods: To elucidate the genetic cause in a patient with very early onset inflammatory bowel disease, we performed whole-exome sequencing and studied the functional consequences of the identified mutation in LY96 (encoding for MD2) in genetically engineered induced pluripotent stem cell-derived macrophages with knockout of MD2 or knockin of the patient-specific mutation, including TLR4-mediated signaling, cytokine production, and bacterial handling. Results: Whole-exome sequencing identified a homozygous in-frame deletion in the LY96 gene (c.347_349delCAA; p.Thr116del) in a patient with very early onset inflammatory bowel disease and a sibling presenting with pneumonia and otitis media. Induced pluripotent stem cell-derived macrophages with knockout of MD2 or expression of the Thr116del mutation showed impaired activation of nuclear factor kappa B and mitogen-activated protein kinase signaling as well as TLR4 endocytosis on challenge with LPS or bacteria. In addition, MD2-deficient macrophages showed decreased cytokine expression (eg, IL-6, TNF, and IL-10) in response to LPS or gram-negative but not gram-positive bacteria. Conclusions: Human MD2 deficiency causes defective TLR4 signaling in response to LPS or gram-negative bacteria. The clinical manifestations and expressivity might be variable due to unknown secondary risk factors. Because TLR4 represents a therapeutic target for multiple inflammatory conditions, our study may provide insights into potential side effects of pharmacological TLR4 targeting.

العلاقة: https://ora.ox.ac.uk/objects/uuid:521f632d-d05b-44d0-a57d-b6a0c373b399Test; https://doi.org/10.1016/j.jaci.2022.09.033Test

الإتاحة: https://doi.org/10.1016/j.jaci.2022.09.033Test
https://ora.ox.ac.uk/objects/uuid:521f632d-d05b-44d0-a57d-b6a0c373b399Test

المؤلفون: Catalano M, Conca R, Petrioli R, Ramello M, Roviello G

المصدر: Cancer Management and Research, Vol Volume 12, Pp 10271-10278 (2020)

مصطلحات موضوعية: irinotecan, oxaliplatin, second line, pancreatic cancer, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282

الوصف: Martina Catalano,1 Raffaele Conca,2 Roberto Petrioli,3 Monica Ramello,4 Giandomenico Roviello5 1School of Human Health Sciences, University of Florence, Florence 50134, Italy; 2Division of Medical Oncology, Department of Onco-Hematology, IRCCS-CROB, Referral Cancer Center of Basilicata, Rionero, Vulture (PZ) 85028, Italy; 3Department of Medicine, Surgery and Neurosciences, Medical Oncology Unit, University of Siena, Siena 53100, Italy; 4Oncology Unit, Department of Medical, Surgical, & Health Sciences, University of Trieste, Trieste, Italy; 5Department of Health Sciences, University of Florence, Florence 50139, ItalyCorrespondence: Giandomenico RovielloDepartment of Health Sciences, University of Florence, Viale Pieraccini, 6, Florence 50139, ItalyTel +055-7938313Email giandomenicoroviello@hotmail.itBackground: Several progresses have been achieved for first-line chemotherapy in metastatic pancreatic ductal adenocarcinoma (PDAC) with Gem-NabP and FOLFIRINOX extensively used as standard first line regimens. However, the best second-line chemotherapy choice after progression is still not completely defined. The aim of this study is to compare effectiveness and safety of two possible second-line therapeutic options, FOLFOX and FOLFIRI, after progression to Gem-NabP.Methods: From January 2015 to December 2018, patients with metastatic PDAC, progressed to the first-line treatment with Gem-NabP, and treated with a fluoropyrimidine-based second-line chemotherapy were considered eligible for our retrospective analysis. Overall survival (OS) and progression free survival (PFS) were set as primary endpoints whereas, disease control rate (DCR) and the rate and severity of treatment-related AEs were secondary endpoints.Results: Overall, 31 patients were treated with Gem-NabP in first-line regimen, 11 received second-line with FOLFOX and 20 with FOLFIRI after progression. Baseline demographic and clinic features were similar in the two groups excluding median age of 55.5 years (range: 50– 73) and 68 years (range: 59– 72) in FOLFIRI and FOLFOX groups, respectively (p=0.002). Median PFS was three months (95%CI: 3– 4), with no significative difference between the two groups. Median OS was eight months (95%CI: 5– 10) and was significantly higher in the FOLFIRI group compared with the FOLFOX group, nine months (95%CI: 7– 17) vs five months (95%CI: 2– 10; p< 0.01). The most commonly reported adverse events were grade 1 or 2 with anemia most frequent in the FOLFOX group (36.4% vs 10.0%) and diarrhea in the FOLFIRI group (40.0% vs 9.1%). Grade 3– 4 adverse events as neutropenia, diarrhea and nausea/vomiting, occurred in 10 patients (32.2%) without differences between the two groups.Conclusion: Our results seem to support the use of fluoropyrimidine-based second-line therapy for patients with metastatic pancreatic cancer, confirming the effectiveness and safety, to a greater extent with FOLFIRI regimen, after progression to the Gem-NabP.Keywords: irinotecan, oxaliplatin, second line, pancreatic cancer

وصف الملف: electronic resource

العلاقة: https://test.dovepress.com/folfox-vs-folfiri-as-second-line-of-therapy-after-progression-to-gemci-peer-reviewed-article-CMARTest; https://doaj.org/toc/1179-1322Test

الوصول الحر: https://doaj.org/article/63ec3935c0ee46808dee23e82ed05400Test

المؤلفون: Ottaviano, M, Curvietto, M, Rescigno, P, Tortora, M, Palmieri, G, Giannarelli, D, Aieta, M, Assalone, P, Attademo, L, Avallone, A, Bloise, F, Bosso, D, Borzillo, V, Buono, G, Calderoni, G, Caputo, F, Cartenì, G, Cavallero, D, Cavo, A, Ciardiello, F, Conca, R, Conteduca, V, De Falco, S, De Felice, M, De Laurentiis, M, De Placido, P, De Placido, S, De Santo, I, De Stefano, A, Della Corte, CM, Di Franco, R, Di Lauro, V, Fabbrocini, A, Federico, P, Festino, L, Giordano, P, Giuliano, M, Gridelli, C, Grimaldi, AM, Lia, M, Marretta, AL, Massa, V, Mennitto, A, Merler, S, Merz, V, Messina, C, Messina, M, Milano, M, Minisini, AM, Montesarchio, V, Morabito, A, Morgillo, F, Mucci, B, Nappi, L, Napolitano, F, Paciolla, I, Pagliuca, M, Parola, S, Pepe, S, Petrillo, A, Piantedosi, F, Piccin, L, Picozzi, F, Pietroluongo, E, Pignata, S, Prati, V, Riccio, V, Rosanova, M, Rossi, A, Russo, A, Salati, M, Santabarbara, G, Sbrana, A, Simeone, E, Silvestri, A, Spada, M, Tarantino, P, Taveggia, P, Tomei, F, Vincenzo, T, Trapani, D, Trojanello, C, Vanella, V, Vari, S, Ventriglia, J, Vitale, MG, Vitiello, F, Vivaldi, C, von Arx, C, Zacchi, F, Zampiva, I, Zivi, A, Daniele, B, Ascierto, PA, SCITO (Società Campana di ImmunoTerapia Oncologica)

المساهمون: Rescigno, Pasquale

مصطلحات موضوعية: SCITO (Società Campana di ImmunoTerapia Oncologica), Humans, Pneumonia, Viral, Coronavirus Infections, Neoplasms, Prevalence, Medical Oncology, Infection Control, Geography, Adult, Italy, Female, Male, Drug Prescriptions, Pandemics, CTLA-4 Antigen, Programmed Cell Death 1 Receptor, Time-to-Treatment, Surveys and Questionnaires, Practice Patterns, Physicians', Oncologists, Betacoronavirus, Antineoplastic Agents, Immunological, B7-H1 Antigen, COVID-19, SARS-CoV-2

الوصف: BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has overwhelmed the health systems worldwide. Data regarding the impact of COVID-19 on cancer patients (CPs) undergoing or candidate for immune checkpoint inhibitors (ICIs) are lacking. We depicted the practice and adaptations in the management of patients with solid tumors eligible or receiving ICIs during the COVID-19 pandemic, with a special focus on Campania region. METHODS: This survey (25 questions), promoted by the young section of SCITO (Società Campana di ImmunoTerapia Oncologica) Group, was circulated among Italian young oncologists practicing in regions variously affected by the pandemic: high (group 1), medium (group 2) and low (group 3) prevalence of SARS-CoV-2-positive patients. For Campania region, the physician responders were split into those working in cancer centers (CC), university hospitals (UH) and general hospitals (GH). Percentages of agreement, among High (H) versus Medium (M) and versus Low (L) group for Italy and among CC, UH and GH for Campania region, were compared by using Fisher's exact tests for dichotomous answers and χ2 test for trends relative to the questions with 3 or more options. RESULTS: This is the first Italian study to investigate the COVID-19 impact on cancer immunotherapy, unique in its type and very clear in the results. The COVID-19 pandemic seemed not to affect the standard practice in the prescription and delivery of ICIs in Italy. Telemedicine was widely used. There was high consensus to interrupt immunotherapy in SARS-CoV-2-positive patients and to adopt ICIs with longer schedule interval. The majority of the responders tended not to delay the start of ICIs; there were no changes in supportive treatments, but some of the physicians opted for delaying surgeries (if part of patients' planned treatment approach). The results from responders in Campania did not differ significantly from the national ones. CONCLUSION: Our study highlights the efforts of Italian oncologists to maintain high standards of care ...

وصف الملف: Print; application/pdf

العلاقة: Journal for immunotherapy of cancer, 2020, 8 (2); https://repository.icr.ac.uk/handle/internal/4346Test

الإتاحة: https://doi.org/10.1136/jitc-2020-001154Test
https://repository.icr.ac.uk/handle/internal/4346Test

المؤلفون: Rubatto M., Fava P., Stanganelli I., Ribero S., Pigozzo J., Di Giacomo A. M., Ridolfi L., Tronconi M. C., Trojaniello C., Bersanelli M., Garutti M., Indini A., De Risi I., De Tursi M., Merelli B., Morgese F., Occelli M., Cappellini G. C. A., Poletto S., Fedele D., Brugnara S., Frisinghelli M., Formisano L., Conca R., Tucci M., Russillo M., Ceroni L., Queirolo P., Targato G., Strippoli S., Mandala' M., Guida M., Quaglino P.

المساهمون: Rubatto, M., Fava, P., Stanganelli, I., Ribero, S., Pigozzo, J., Di Giacomo, A. M., Ridolfi, L., Tronconi, M. C., Trojaniello, C., Bersanelli, M., Garutti, M., Indini, A., De Risi, I., De Tursi, M., Merelli, B., Morgese, F., Occelli, M., Cappellini, G. C. A., Poletto, S., Fedele, D., Brugnara, S., Frisinghelli, M., Formisano, L., Conca, R., Tucci, M., Russillo, M., Ceroni, L., Queirolo, P., Targato, G., Strippoli, S., Mandala', M., Guida, M., Quaglino, P.

مصطلحات موضوعية: Discontinuation of immunotherapy, Metastatic melanoma therapy, Real-life study

الوصف: Background: Immunotherapy has improved the survival of patients with stage IV melanoma. In responders, clinical benefits may be long-lasting and persist even after treatment discontinuation. The optimal duration of anti-PD1 (anti-Programmed cell death-1) therapy in metastatic melanoma patients remains to be elucidated. Moreover, limited data are available on clinical outcomes of patients that discontinued anti-PD1 immunotherapy in a real-life setting. The aim of this study was to evaluate the progression-free survival (PFS) in patients with metastatic melanoma who interrupted anti-PD-1 treatment in the in the absence of disease progression. Methods: We retrospectively reviewed patients with advanced/metastatic melanoma treated with anti-PD1 immunotherapy at 23 Italian Melanoma Intergroup (IMI) centres. The study investigated the risk of relapse in patients who stopped anti-PD1 therapy due to CR (Complete response), treatment-related toxicity, or by their own choice after a long period of treatment. Clinical and biological factors associated with or without recurrence were evaluated. Results: The study population included 237 patients. The median age of patients was 68.9 years (standard deviation: 13; range 33–95). The median time on treatment was 33 months (standard deviation: 18, 7; range 1–98). Among the 237 patients, 128 (54%) interrupted the anti-PD1 for CR, 74 patients (31.2%) for adverse events (37 patients in CR, 27 patients in partial response (PR), ten patients in stable disease (SD), and 35 patients (14.8%) by their own choice (12 patients in CR, 17 patients in PR, and 6 patients in SD). After a mean follow-up of 21 months (range 1–81), PFS after anti-PD1 discontinuation was 85.7%. Thirty-four patients (14.3%) developed disease progression after a median of 12 months (range 1–35): ten patients (29.4%) after discontinuation in CR, 17 patients (50%) after discontinuation for treatment-related toxicity (seven in CR, five in PR, five in SD), and seven (20.6%) after discontinuation due to the patient's ...

العلاقة: info:eu-repo/semantics/altIdentifier/pmid/37099946; info:eu-repo/semantics/altIdentifier/wos/WOS:000994560100001; volume:187; firstpage:25; lastpage:35; numberofpages:11; journal:EUROPEAN JOURNAL OF CANCER; https://hdl.handle.net/11391/1566840Test; info:eu-repo/semantics/altIdentifier/scopus/2-s2.0-85153403676

الإتاحة: https://doi.org/10.1016/j.ejca.2023.03.020Test
https://hdl.handle.net/11391/1566840Test

المؤلفون: Roviello G., Corona S., Conca R., Petrioli R., Rosellini P., Bonetta A., Aieta M.

المساهمون: Roviello, G., Corona, S., Conca, R., Petrioli, R., Rosellini, P., Bonetta, A., Aieta, M.

مصطلحات موضوعية: chemotherapy, prostate cancer, vinorelbine, Administration, Oral, Aged, 80 and over, Antineoplastic Agents, Phytogenic, Bone Neoplasm, Human, Male, Middle Aged, Neoplasm Staging, Prostatic Neoplasms, Castration-Resistant, Treatment Outcome

الوصف: The aim of this paper was to evaluate the activity and tolerability of oral vinorelbine in patients with advanced castration resistant prostate cancer (CRPC) who progressed after a minimum of three lines including: abiraterone acetate, docetaxel, cabazitaxel, and enzalutamide.Treatment consisted of weekly oral vinorelbine 60 mg/m. Chemotherapy was administered until disease progression or unacceptable toxicity.Twenty-six patients received vinorelbine: their median age was 74 years (range 58-84 years). Twenty-four (92.3%) patients had bone metastases. A decrease in PSA levels ≥50% was observed in 2 patients (7.7%). Among the subjects who were symptomatic at baseline, pain was reduced in 3 patients (13.6%) with a significant decrease in analgesic use. Median progression-free survival was 9 weeks (95% CI: 7 to 11) and median overall survival was 17 weeks (95% CI: 12 to 22). Treatment was well tolerated, and no grade 4 toxicities were observed.Our findings do not suggest the use of oral vinorelbine on a weekly schedule, in CRPC heavily pre-treated

وصف الملف: ELETTRONICO

العلاقة: info:eu-repo/semantics/altIdentifier/pmid/31261590; info:eu-repo/semantics/altIdentifier/wos/WOS:000480733400100; volume:98; issue:26; firstpage:"-"; lastpage:"-"; numberofpages:5; journal:MEDICINE; http://hdl.handle.net/11368/2961382Test; info:eu-repo/semantics/altIdentifier/scopus/2-s2.0-85069268829; https://journals.lww.com/md-journal/fulltext/2019/06280/Is_there_still_a_place_for_vinorelbine_in_advanced.101.aspxTest

الإتاحة: https://doi.org/10.1097/MD.0000000000016249Test
http://hdl.handle.net/11368/2961382Test
https://journals.lww.com/md-journal/fulltext/2019/06280/Is_there_still_a_place_for_vinorelbine_in_advanced.101.aspxTest

المؤلفون: Roviello G., Corona S., Bozza G., Aieta M., Generali D., Rodriquenz M. G., Mileo A. M., Imperatori M., Ianza A., Conca R., Sobhani N.

المساهمون: Roviello, G., Corona, S., Bozza, G., Aieta, M., Generali, D., Rodriquenz, M. G., Mileo, A. M., Imperatori, M., Ianza, A., Conca, R., Sobhani, N.

مصطلحات موضوعية: c-KIT, FGFR1–4, Lenvatinib, PDGFRα, Renal cell carcinoma, RET, VEGFR1–3, Angiogenesis Inhibitor, Animal, Antineoplastic Combined Chemotherapy Protocol, Carcinoma, Renal Cell, Everolimu, Human, Kidney Neoplasm, Phenylurea Compound, Protein Kinase Inhibitor, Quinoline, Vascular Endothelial Growth Factor A

الوصف: Introduction: Renal cell carcinoma (RCC) accounts for 2–3% of all solid tumors. Expression of the receptor for the vascular endothelial growth factor (VEGF) is one of the most common features of RCC. Areas covered: Lenvatinib is a novel multi-kinase inhibitor that has been studied in several solid tumors. It has shown promising results in the treatment of RCC, especially when combined with everolimus, In this review, we summarize the available data of lenvatinib for the treatment of advanced/metastatic renal cell carcinoma. Expert opinion: Lenvatinib in combination with everolimus has provided encouraging results in both clinical and laboratory investigations showing that blocking angiogenesis and the mTOR signalling pathway could be a remarkable approach for treating RCC. As an additive to this type of approach it would be interesting in future clinical settings testing also the combination of lenvatinib and everolimus with immune-therapy.

وصف الملف: STAMPA

العلاقة: info:eu-repo/semantics/altIdentifier/pmid/29718721; info:eu-repo/semantics/altIdentifier/wos/WOS:000432689500008; volume:27; issue:5; firstpage:507; lastpage:512; numberofpages:6; journal:EXPERT OPINION ON INVESTIGATIONAL DRUGS; http://hdl.handle.net/11368/2961370Test; info:eu-repo/semantics/altIdentifier/scopus/2-s2.0-85047307780

الإتاحة: https://doi.org/10.1080/13543784.2018.1472235Test
http://hdl.handle.net/11368/2961370Test

المؤلفون: Passiglia F, Commendatore O, Vitali M, Conca R

المساهمون: Passiglia F, Commendatore O, Vitali M, Conca R

مصطلحات موضوعية: NSCLC, PD-1, PD-L1, biomarker, cancer immunogenicity, clinical studie, immune checkpoint inhibitor, translational research, Settore MED/06 - Oncologia Medica

الوصف: Lung cancer has been historically considered a poorly immunogenic disease because of the few evidence of immune responses in affected patients and the limited efficacy of immunomodulating strategies. Recent understanding of the molecular mechanisms leading to cancer immune evasion has allowed the development of a new class of drugs called immune checkpoint inhibitors, which reactivate host responses with outstanding clinical benefits in a portion of patients with non-small-cell lung cancer. In this review, we briefly summarize the basis of immunogenicity and immune escape of cancer, with specific focus on non-small-cell lung cancer, mechanisms underlying immune checkpoint inhibitors efficacy and the most updated results on potential biomarkers, with the final aim of defining current unmet needs of immunotherapy in clinical practice.

العلاقة: info:eu-repo/semantics/altIdentifier/pmid/2-s2.0-85050010879; info:eu-repo/semantics/altIdentifier/wos/WOS:000438052800005; volume:14; firstpage:41; lastpage:60; numberofpages:20; journal:FUTURE ONCOLOGY; http://hdl.handle.net/10447/295576Test; info:eu-repo/semantics/altIdentifier/scopus/2-s2.0-85050010879

الإتاحة: https://doi.org/10.2217/fon-2018-0098Test
http://hdl.handle.net/10447/295576Test

المؤلفون: Li, Y, Yu, Z, Schenk, M, Lagovsky, I, Illig, D, Walz, C, Rohlfs, M, Conca, R, Muise, A, Snapper, S, Uhlig, H, Garty, B, Klein, C, Kotlarz, D

المصدر: Journal of Crohn's and Colitis ; volume 17, issue Supplement_1, page i97-i97 ; ISSN 1873-9946 1876-4479

مصطلحات موضوعية: Gastroenterology, General Medicine

الوصف: Background Pattern recognition receptors (PRRs) serve as a hub of immune responses to microbes in the gut and play a critical role in maintaining intestinal homeostasis. Toll-like receptor 4 (TLR4) represents an important PRR that can recognize the gram-negative bacterial cell wall component lipopolysaccharide (LPS). Upon binding to LPS, TLR4 forms a multimeric complex with the indispensable co-receptor myeloid differentiation protein 2 (MD2) facilitating selection of TLR4 as cargo for endocytosis and TLR4-mediated activation of downstream signalling. Despite the critical role of TLR4 in innate immunity, no patients with TLR4 or MD2 deficiency have yet been reported. Methods To investigate potential genetic causes for two related patients presenting with very early onset Inflammatory Bowel Disease (VEO-IBD) and/or pneumonia, we have performed whole exome sequencing (WES). To assess the functional consequences of the identified LY96 (encoding for MD2) variant, we generated a CRISPR/Cas9-mediated knockout (KO) of MD2 or knockin (KI) of the patient mutation in induced pluripotent stem cells (iPSCs) and studied TLR4-mediated signalling, cytokine responses, and bacterial handling in iPSC-derived macrophages. Results Genetic analysis identified a 3 bp homozygous in-frame deletion in the LY96 gene (NM_015364.5, c.347_349delCAA; p.Thr116del) in our index patients following an autosomal recessive inheritance pattern. Immunoblotting revealed an altered protein expression of overexpressed Flag-tagged mutant MD2 protein due to impaired N-linked glycosylation. Correspondingly, iPSC-derived MD2-deficient macrophages showed an impaired LPS-induced TLR4 endocytosis. As a functional consequence, we could detect reduced NF-κB and MAPK signalling (phosphorylation of NF-κB p65 subunit, ERK1/2, and p38 MAPK) and dysregulated inflammasome activation (IL-1b production and secretion) upon challenge with LPS. Gentamycin protection assays and live cell imaging suggested that MD2-deficient macrophages exhibit an impaired ...

الإتاحة: https://doi.org/10.1093/ecco-jcc/jjac190.0074Test
https://academic.oup.com/ecco-jcc/article-pdf/17/Supplement_1/i97/51509199/jjac190.0074.pdfTest

المؤلفون: Aline Jorquera L., Jan Wilhelm B., Natalia Conca R.

المصدر: Revista chilena de infectología. 39:448-456

مصطلحات موضوعية: Infectious Diseases, Public Health, Environmental and Occupational Health

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_________::635c8e3da558c8e9c36bc73f8e8301fcTest
https://doi.org/10.4067/s0716-10182022000400448Test

المؤلفون: Roviello G., Gambale E., Giorgione R., Santini D., Stellato M., Fornarini G., Rebuzzi S. E., Basso U., Bimbatti D., Doni L., Nesi G., Bersanelli M., Buti S., De Giorgi U., Galli L., Sbrana A., Conca R., Carella C., Naglieri E., Pignata S., Procopio G., Antonuzzo L.

المساهمون: Roviello, G., Gambale, E., Giorgione, R., Santini, D., Stellato, M., Fornarini, G., Rebuzzi, S. E., Basso, U., Bimbatti, D., Doni, L., Nesi, G., Bersanelli, M., Buti, S., De Giorgi, U., Galli, L., Sbrana, A., Conca, R., Carella, C., Naglieri, E., Pignata, S., Procopio, G., Antonuzzo, L.

مصطلحات موضوعية: fourth-line therapy, immune checkpoint inhibitor, metastatic renal cell carcinoma, targeted therapy, tyrosine kinase inhibitor, vascular endothelial growth factor receptor

الوصف: Background: Nivolumab and cabozantinib are currently approved agents in metastatic renal cell carcinoma (mRCC) but there are no data available for patients progressing to both treatments. The aim of this study was to compare active therapeutic options and best supportive care (BSC) after progression to nivolumab and cabozantinib in mRCC. Methods: In this retrospective study, we selected 50 patients from eight Italian centers. The primary endpoint of the study was the overall survival (OS) of patients on active treatment versus BSC. Secondary endpoints were the progression-free survival (PFS) and objective response rate (ORR). The efficacy of active therapy was also investigated. Results: After progression to both nivolumab and cabozantinib, 57.1% of patients were given active treatment (mainly everolimus and sorafenib) while 42.9% received BSC. The median OS was 13months (95% CI: 4-NR) in actively treated patients and 3months (95% CI: 2–4) in BSC patients (p=0.001). Patients treated with sorafenib had better disease control than those treated with everolimus (stable disease: 71.4% vs. 16.7%, progression disease: 14.3% vs. 58.3%; p=0.03), with no significant differences in PFS (5 and 3months, 95% CI: 1–6 vs. 2–5; p=0.6) and OS (12 and 4months, 95% CI: 3-NR vs. 2-NR; p=0.2). Conclusion: After treatment with both nivolumab and cabozantinib, the choice of a safe active systemic therapy offered better outcomes than BSC.

العلاقة: info:eu-repo/semantics/altIdentifier/pmid/35312175; info:eu-repo/semantics/altIdentifier/wos/WOS:000770847900001; journal:CANCER MEDICINE; https://hdl.handle.net/11573/1641667Test; info:eu-repo/semantics/altIdentifier/scopus/2-s2.0-85126550504

الإتاحة: https://doi.org/10.1002/cam4.4681Test
https://hdl.handle.net/11573/1641667Test