Search

Your search keyword '"Zoratto, F"' showing total 11 results
Start Over Author "Zoratto, F" Publisher elsevier
11 results on '"Zoratto, F"'

1. Post-progression outcomes of NSCLC patients with PD-L1 expression ≥ 50% receiving first-line single-agent pembrolizumab in a large multicentre real-world study

Author

Cortellini, A, Cannita, K, Tiseo, M, Cortinovis, D, Aerts, J, Baldessari, C, Giusti, R, Ferrara, M, D'Argento, E, Grossi, F, Guida, A, Berardi, R, Morabito, A, Genova, C, Antonuzzo, L, Mazzoni, F, De Toma, A, Signorelli, D, Gelibter, A, Targato, G, Rastelli, F, Chiari, R, Rocco, D, Gori, S, De Tursi, M, Mansueto, G, Zoratto, F, Filetti, M, Bracarda, S, Citarella, F, Russano, M, Cantini, L, Nigro, O, Buti, S, Minuti, G, Landi, L, Ricciardi, S, Migliorino, M, Natalizio, S, Simona, C, De Filippis, M, Metro, G, Adamo, V, Russo, A, Spinelli, G, Di Maio, M, Banna, G, Friedlaender, A, Addeo, A, Pinato, D, Ficorella, C, Porzio, G, Cortellini A, Cannita K, Tiseo M, Cortinovis D, Aerts JGJV, Baldessari C, Giusti R, Ferrara MG, D'Argento E, Grossi F, Guida A, Berardi R, Morabito A, Genova C, Antonuzzo L, Mazzoni F, De Toma A, Signorelli D, Gelibter A, Targato G, Rastelli F, Chiari R, Rocco D, Gori S, De Tursi M, Mansueto G, Zoratto F, Filetti M, Bracarda S, Citarella F, Russano M, Cantini L, Nigro O, Buti S, Minuti G, Landi L, Ricciardi S, Migliorino MR, Natalizio S, Simona C, De Filippis M, Metro G, Adamo V, Russo A, Spinelli GP, Di Maio M, Banna GL, Friedlaender A, Addeo A, Pinato DJ, Ficorella C, Porzio G, Cortellini, A, Cannita, K, Tiseo, M, Cortinovis, D, Aerts, J, Baldessari, C, Giusti, R, Ferrara, M, D'Argento, E, Grossi, F, Guida, A, Berardi, R, Morabito, A, Genova, C, Antonuzzo, L, Mazzoni, F, De Toma, A, Signorelli, D, Gelibter, A, Targato, G, Rastelli, F, Chiari, R, Rocco, D, Gori, S, De Tursi, M, Mansueto, G, Zoratto, F, Filetti, M, Bracarda, S, Citarella, F, Russano, M, Cantini, L, Nigro, O, Buti, S, Minuti, G, Landi, L, Ricciardi, S, Migliorino, M, Natalizio, S, Simona, C, De Filippis, M, Metro, G, Adamo, V, Russo, A, Spinelli, G, Di Maio, M, Banna, G, Friedlaender, A, Addeo, A, Pinato, D, Ficorella, C, Porzio, G, Cortellini A, Cannita K, Tiseo M, Cortinovis D, Aerts JGJV, Baldessari C, Giusti R, Ferrara MG, D'Argento E, Grossi F, Guida A, Berardi R, Morabito A, Genova C, Antonuzzo L, Mazzoni F, De Toma A, Signorelli D, Gelibter A, Targato G, Rastelli F, Chiari R, Rocco D, Gori S, De Tursi M, Mansueto G, Zoratto F, Filetti M, Bracarda S, Citarella F, Russano M, Cantini L, Nigro O, Buti S, Minuti G, Landi L, Ricciardi S, Migliorino MR, Natalizio S, Simona C, De Filippis M, Metro G, Adamo V, Russo A, Spinelli GP, Di Maio M, Banna GL, Friedlaender A, Addeo A, Pinato DJ, Ficorella C, and Porzio G

Abstract

Background: Treatment sequencing with first-line immunotherapy, followed by second-line chemotherapy, is still a viable option for NSCLC patients with PD-L1 expression ≥50%. Methods: We evaluated post-progression treatment pathways in a large real-world cohort of metastatic NSCLC patients with PD-L1 expression ≥ 50% treated with first-line pembrolizumab monotherapy. Results: Overall, 974 patients were included. With a median follow-up of 22.7 months (95%CI: 21.6–38.2), the median overall survival (OS) of the entire population was 15.8 months (95%CI: 13.5–17.5; 548 events). At the data cutoff, among the 678 patients who experienced disease progression, 379 (55.9%) had not received any further treatment, and 359 patients (52.9%) had died. Patients who did not receive post-progression therapies were older (p = 0.0011), with a worse ECOG-PS (p < 0.0001) and were on corticosteroids prior to pembrolizumab (p = 0.0024). At disease progression, 198 patients (29.2%) received a switched approach and 101 (14.9%) received pembrolizumab ByPD either alone (64 [9.4%]) or in combination with local ablative treatments (37 [5.5%]) (LATs). After a random-case control matching according to ECOG-PS, CNS metastases, bone metastases, and (previous) best response to pembrolizumab, patients receiving pembrolizumab ByPD plus LATs were confirmed to have a significantly longer post-progression OS compared to patients receiving pembrolizumab ByPD alone 13.9 months versus 7.8 months (p = 0.0179) 241 patients (35.5%) among the 678 who had experienced PD, received a second-line systemic treatment (regardless of previous treatment beyond PD). As compared to first-line treatment commencement, patients’ features at the moment of second-line initiation showed a significantly higher proportion of patients aged under 70 years (p = 0.0244), with a poorer ECOG-PS (p < 0.0001) and having CNS (p = 0.0001), bone (p = 0.0266) and liver metastases (p = 0.0148). Conclusions: In the real-world scenario NSC

Published
2021

2. Immune-related Adverse Events of Pembrolizumab in a Large Real-world Cohort of Patients With NSCLC With a PD-L1 Expression ≥ 50% and Their Relationship With Clinical Outcomes

Author

Cortellini, A, Friedlaender, A, Banna, G, Porzio, G, Bersanelli, M, Cappuzzo, F, Aerts, J, Giusti, R, Bria, E, Cortinovis, D, Grossi, F, Migliorino, M, Galetta, D, Passiglia, F, Berardi, R, Mazzoni, F, Di Noia, V, Signorelli, D, Tuzi, A, Gelibter, A, Marchetti, P, Macerelli, M, Rastelli, F, Chiari, R, Rocco, D, Inno, A, Di Marino, P, Mansueto, G, Zoratto, F, Santoni, M, Tudini, M, Ghidini, M, Filetti, M, Catino, A, Pizzutilo, P, Sala, L, Occhipinti, M, Citarella, F, Marco, R, Torniai, M, Cantini, L, Follador, A, Sforza, V, Nigro, O, Ferrara, M, D'Argento, E, Leonetti, A, Pettoruti, L, Antonuzzo, L, Scodes, S, Landi, L, Guaitoli, G, Baldessari, C, Bertolini, F, Della Gravara, L, Dal Bello, M, Belderbos, R, De Filippis, M, Cecchi, C, Ricciardi, S, Donisi, C, De Toma, A, Proto, C, Addeo, A, Cantale, O, Ricciuti, B, Genova, C, Morabito, A, Santini, D, Ficorella, C, Cannita, K, Cortellini A, Friedlaender A, Banna GL, Porzio G, Bersanelli M, Cappuzzo F, Aerts JGJV, Giusti R, Bria E, Cortinovis D, Grossi F, Migliorino MR, Galetta D, Passiglia F, Berardi R, Mazzoni F, Di Noia V, Signorelli D, Tuzi A, Gelibter A, Marchetti P, Macerelli M, Rastelli F, Chiari R, Rocco D, Inno A, Di Marino P, Mansueto G, Zoratto F, Santoni M, Tudini M, Ghidini M, Filetti M, Catino A, Pizzutilo P, Sala L, Occhipinti MA, Citarella F, Marco R, Torniai M, Cantini L, Follador A, Sforza V, Nigro O, Ferrara MG, D'Argento E, Leonetti A, Pettoruti L, Antonuzzo L, Scodes S, Landi L, Guaitoli G, Baldessari C, Bertolini F, Della Gravara L, Dal Bello MG, Belderbos RA, De Filippis M, Cecchi C, Ricciardi S, Donisi C, De Toma A, Proto C, Addeo A, Cantale O, Ricciuti B, Genova C, Morabito A, Santini D, Ficorella C, Cannita K., Cortellini, A, Friedlaender, A, Banna, G, Porzio, G, Bersanelli, M, Cappuzzo, F, Aerts, J, Giusti, R, Bria, E, Cortinovis, D, Grossi, F, Migliorino, M, Galetta, D, Passiglia, F, Berardi, R, Mazzoni, F, Di Noia, V, Signorelli, D, Tuzi, A, Gelibter, A, Marchetti, P, Macerelli, M, Rastelli, F, Chiari, R, Rocco, D, Inno, A, Di Marino, P, Mansueto, G, Zoratto, F, Santoni, M, Tudini, M, Ghidini, M, Filetti, M, Catino, A, Pizzutilo, P, Sala, L, Occhipinti, M, Citarella, F, Marco, R, Torniai, M, Cantini, L, Follador, A, Sforza, V, Nigro, O, Ferrara, M, D'Argento, E, Leonetti, A, Pettoruti, L, Antonuzzo, L, Scodes, S, Landi, L, Guaitoli, G, Baldessari, C, Bertolini, F, Della Gravara, L, Dal Bello, M, Belderbos, R, De Filippis, M, Cecchi, C, Ricciardi, S, Donisi, C, De Toma, A, Proto, C, Addeo, A, Cantale, O, Ricciuti, B, Genova, C, Morabito, A, Santini, D, Ficorella, C, Cannita, K, Cortellini A, Friedlaender A, Banna GL, Porzio G, Bersanelli M, Cappuzzo F, Aerts JGJV, Giusti R, Bria E, Cortinovis D, Grossi F, Migliorino MR, Galetta D, Passiglia F, Berardi R, Mazzoni F, Di Noia V, Signorelli D, Tuzi A, Gelibter A, Marchetti P, Macerelli M, Rastelli F, Chiari R, Rocco D, Inno A, Di Marino P, Mansueto G, Zoratto F, Santoni M, Tudini M, Ghidini M, Filetti M, Catino A, Pizzutilo P, Sala L, Occhipinti MA, Citarella F, Marco R, Torniai M, Cantini L, Follador A, Sforza V, Nigro O, Ferrara MG, D'Argento E, Leonetti A, Pettoruti L, Antonuzzo L, Scodes S, Landi L, Guaitoli G, Baldessari C, Bertolini F, Della Gravara L, Dal Bello MG, Belderbos RA, De Filippis M, Cecchi C, Ricciardi S, Donisi C, De Toma A, Proto C, Addeo A, Cantale O, Ricciuti B, Genova C, Morabito A, Santini D, Ficorella C, and Cannita K.

Abstract

Background: The role of immune-related adverse events (irAEs), as a surrogate predictor of the efficacy of checkpoint inhibitors, has not yet been described in the setting of first-line, single-agent pembrolizumab for patients with metastatic non-small-cell lung-cancer (NSCLC) with a programmed death-ligand 1 (PD-L1) expression of ≥ 50%. Patients and methods: We previously conducted a multicenter retrospective analysis in patients with treatment-naive metastatic NSCLC and a PD-L1 expression of ≥ 50% receiving first-line pembrolizumab. Here, we report the results of the irAE analysis and the potential correlation between irAEs and clinical outcomes. Results: A total of 1010 patients were included in this analysis; after a 6-week landmark selection, 877 (86.8%) patients were included in the efficacy analysis. Any grade irAEs (P < .0001), grade 3/4 irAEs (P = .0025), leading to discontinuation irAEs (P = .0144), multiple-site and single-site irAEs (P < .0001), cutaneous irAEs (P = .0001), endocrine irAEs (P = .0227), pulmonary irAEs (P = .0479), and rheumatologic irAEs (P = .0018) were significantly related to a higher objective response rate. Any grade irAEs (P < .0001), single-site irAEs (P < .0001), multiple-site irAEs (P = .0005), cutaneous irAEs (P = .0042), endocrine irAEs (P < .0001), gastrointestinal irAEs (P = .0391), and rheumatologic irAEs (P = .0086) were significantly related to progression-free survival. Any grade irAEs (P < .0001), single-site irAEs (P < .0001), multiple-site irAEs (P = .0003), cutaneous irAEs (P = .0002), endocrine irAEs (P = .0001), and rheumatologic irAEs (P = .0214) were significantly related to overall survival. Conclusions: This study confirms the feasibility and the safety of first-line, single-agent pembrolizumab, in a large, real-world cohort of patients with NSCLC with PD-L1 expression ≥ 50%. The occurrence of irAEs may be a surrogate of clinical activity and improved outcomes in this setting.

Published
2020

5. Comparing fast-acting interventions for treatment-resistant depression: An explorative study of accelerated HF-rTMS versus intranasal esketamine.

Author

Pettorruso M, d'Andrea G, Di Carlo F, De Risio L, Zoratto F, Miuli A, Benatti B, Vismara M, Pompili E, Nicolò G, Niolu C, Siracusano A, Sensi SS, Dell'Osso B, Di Lorenzo G, and Martinotti G

Subjects
Humans, Depression, Antidepressive Agents therapeutic use, Transcranial Magnetic Stimulation, Treatment Outcome, Ketamine pharmacology, Ketamine therapeutic use, Depressive Disorder, Treatment-Resistant therapy
Abstract

Competing Interests: Declaration of competing interest Giovanni Martinotti has been a consultant and/or a speaker and/or has received research grants from Angelini, Doc Generici, Janssen-Cilag, Lundbeck, Otsuka, Pfizer, Servier, and Recordati. Bernardo Dell'Osso has received lecture honoraria from Angelini, Lundbeck, Janssen, Pfizer, Neuraxpharm, Arcapharma, and Livanova. Giorgio Di Lorenzo has been a speaker and/or a consultant for Angelini, FB-Health, Janssen-Cilag, Livanova, Lundbeck, Neuraxpharm, Otsuka, and Recordati. The remaining authors declare that the research was conducted without any commercial or financial relationship that could be construed as a potential conflict of interest.

Published
2023
Full Text
View/download PDF

6. Clinicians' Attitude to Doublet Plus Anti-EGFR Versus Triplet Plus Bevacizumab as First-line Treatment in Left-Sided RAS and BRAF Wild-Type Metastatic Colorectal Cancer Patients: A Multicenter, "Real-Life", Case-Control Study.

Author

Parisi A, Porzio G, Cannita K, Venditti O, Avallone A, Filippi R, Salvatore L, Tortora G, Ribelli M, Nigro O, Gelsomino F, Spallanzani A, Zurlo V, Leo S, Dell'Aquila E, Claudia F, Lombardi P, Keränen SR, Aimar G, Depetris I, Giampieri R, Morelli C, De Tursi M, Tinari N, Di Pietro FR, De Galitiis F, Zanaletti N, Troiani T, Vitale P, Garajova I, Ghidini M, Spinelli GP, Zoratto F, Roberto M, Ierino D, Petrillo A, D'Orazio C, Ficorella C, and Cortellini A

Subjects
Antineoplastic Combined Chemotherapy Protocols therapeutic use, Bevacizumab therapeutic use, Case-Control Studies, Fluorouracil therapeutic use, Humans, Retrospective Studies, Colorectal Neoplasms drug therapy, Colorectal Neoplasms genetics, Proto-Oncogene Proteins B-raf genetics
Abstract

Background: Doublets plus antiepidermal growth factor receptors monoclonal antibodies (EGFRi) are widely considered the preferable first-line regimen in patients with left-sided RAS/BRAF wild-type metastatic colorectal cancer (mCRC), resulting superior in terms of activity and efficacy compared to doublets plus bevacizumab. However, data comparing doublet plus EGFRi and triplet plus bevacizumab are lacking, and the relative benefit of an intensive regimen plus an antiangiogenic backbone in this population is debated., Methods: This multicenter, retrospective study aimed at evaluating clinicians' attitude to triplet-bevacizumab and doublet-EGFRi as first-line regimen in patients with left-sided RAS/BRAF wild-type mCRC treated in clinical practice at 22 Oncology Units from March 2012 to October 2020. A random case-control matching was performed to compare activity (ORR), and effectiveness (PFS, OS, secondary resection rate of metastases with curative intent) between triplet-bevacizumab and doublet-EGFRi, on the basis of ECOG-PS, age, gender, and burden of disease., Results: A total of 718 patients were consecutively treated with doublet-EGFRi (686, 95.5%) or triplet-bevacizumab (32, 4.5%). After case-control matching, median PFS was 13.6 (95% CI, 8.9-31.7) and 16.1 (95% CI, 12.1-36.8) months (P= .621), while median OS was 30.2 (95% CI, 14.4-69.5) and 38.1 (95% CI, 33.1-101.1) months (P= .0283) in the doublet-EGFRi and the triplet-bevacizumab cohort, respectively. The ORR was 65.6% and 90.6% (P= .016), while the secondary resection rate was 18.8% and 46.9% (P= .016), in the doublet-EGFRi and the triplet-bevacizumab cohort, respectively. Triplet-bevacizumab was associated with a higher incidence of G3/G4 neutropenia (25.0% vs. 12.5%, P= .041)., Conclusion: Although a doublet-EGFRi remains the recommended upfront regimen in patients with left-sided RAS and BRAF wild-type mCRC, our real life data suggest a triplet-bevacizumab might be at least equally active and effective in properly selected cases., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Published
2021
Full Text
View/download PDF

7. Corrigendum to 'The lung immuno-oncology prognostic score (LIPS-3): a prognostic classification of patients receiving first-line pembrolizumab for PD-L1 ≥ 50% advanced non-small-cell lung cancer': [ESMO Open Volume 6, Issue 2, April 2021, 100078].

Author

Banna GL, Cortellini A, Cortinovis DL, Tiseo M, Aerts JGJV, Barbieri F, Giusti R, Bria E, Grossi F, Pizzutilo P, Berardi R, Morabito A, Genova C, Mazzoni F, Di Noia V, Signorelli D, Gelibter A, Macerelli M, Rastelli F, Chiari R, Rocco D, Gori S, De Tursi M, Di Marino P, Mansueto G, Zoratto F, Filetti M, Montrone M, Citarella F, Marco R, Cantini L, Nigro O, D'Argento E, Buti S, Minuti G, Landi L, Guaitoli G, Lo Russo G, De Toma A, Donisi C, Friedlaender A, De Giglio A, Metro G, Porzio G, Ficorella C, and Addeo A

Published
2021
Full Text
View/download PDF

8. The lung immuno-oncology prognostic score (LIPS-3): a prognostic classification of patients receiving first-line pembrolizumab for PD-L1 ≥ 50% advanced non-small-cell lung cancer.

Author

Banna GL, Cortellini A, Cortinovis DL, Tiseo M, Aerts JGJV, Barbieri F, Giusti R, Bria E, Grossi F, Pizzutilo P, Berardi R, Morabito A, Genova C, Mazzoni F, Di Noia V, Signorelli D, Gelibter A, Macerelli M, Rastelli F, Chiari R, Rocco D, Gori S, De Tursi M, Di Marino P, Mansueto G, Zoratto F, Filetti M, Montrone M, Citarella F, Marco R, Cantini L, Nigro O, D'Argento E, Buti S, Minuti G, Landi L, Guaitoli G, Lo Russo G, De Toma A, Donisi C, Friedlaender A, De Giglio A, Metro G, Porzio G, Ficorella C, and Addeo A

Subjects
Antibodies, Monoclonal, Humanized, B7-H1 Antigen, Humans, Lung, Prognosis, Retrospective Studies, Carcinoma, Non-Small-Cell Lung diagnosis, Carcinoma, Non-Small-Cell Lung drug therapy, Lung Neoplasms diagnosis, Lung Neoplasms drug therapy
Abstract

Background: To stratify the prognosis of patients with programmed cell death-ligand 1 (PD-L1) ≥ 50% advanced non-small-cell lung cancer (aNSCLC) treated with first-line immunotherapy., Methods: Baseline clinical prognostic factors, the neutrophil-to-lymphocyte ratio (NLR), PD-L1 tumour cell expression level, lactate dehydrogenase (LDH) and their combination were investigated by a retrospective analysis of 784 patients divided between statistically powered training (n = 201) and validation (n = 583) cohorts. Cut-offs were explored by receiver operating characteristic (ROC) curves and a risk model built with validated independent factors by multivariate analysis., Results: NLR < 4 was a significant prognostic factor in both cohorts (P < 0.001). It represented 53% of patients in the validation cohort, with 1-year overall survival (OS) of 76.6% versus 44.8% with NLR > 4, in the validation series. The addition of PD-L1 ≥ 80% (21% of patients) or LDH < 252 U/l (25%) to NLR < 4 did not result in better 1-year OS (of 72.6% and 74.1%, respectively, in the validation cohort). Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 2 [P < 0.001, hazard ratio (HR) 2.04], pretreatment steroids (P < 0.001, HR 1.67) and NLR < 4 (P < 0.001, HR 2.29) resulted in independent prognostic factors. A risk model with these three factors, namely, the lung immuno-oncology prognostic score (LIPS)-3, accurately stratified three OS risk-validated categories of patients: favourable (0 risk factors, 40%, 1-year OS of 78.2% in the whole series), intermediate (1 or 2 risk factors, 54%, 1-year OS 53.8%) and poor (>2 risk factors, 5%, 1-year OS 10.7%) prognosis., Conclusions: We advocate the use of LIPS-3 as an easy-to-assess and inexpensive adjuvant prognostic tool for patients with PD-L1 ≥ 50% aNSCLC., Competing Interests: Disclosure AC received speaker fees and grant consultancies from AstraZeneca, MSD, BMS, Roche, Novartis and Astellas. EB received speaker and travel fees from MSD, Astra-Zeneca, Pfizer, Helsinn, Eli-Lilly, BMS, Novartis and Roche; received grant consultancies from Roche and Pfizer. MT received speaker fees and grant consultancies from AstraZeneca, Pfizer, Eli-Lilly, BMS, Novartis, Roche, MSD, Boehringer Ingelheim, Otsuka, Takeda and Pierre Fabre. AM received speaker fees from Astra, Roche, BMS, MSD, Boehringer, Pfizer and Takeda. FM received grant consultancies from MSD and Takeda. RG received speaker fees and grant consultancies from AstraZeneca and Roche. AF received grant consultancies from Roche, Pfizer, Astellas and BMS. AA received grant consultancies from Takeda, MSD, BMJ, AstraZeneca, Roche and Pfizer. RC received speaker fees from BMS, MSD, Takeda, Pfizer, Roche and AstraZeneca. CG received speaker fees/grant consultancies from Astra Zeneca, BMS and Boehringer-Ingelheim. GLB personal fees from Janssen Cilag, Boehringer Ingelheim, AstraZeneca and Roche, outside the submitted work. All other authors have declared no conflicts of interest. Data sharing The datasets used during this study are available from the corresponding author upon reasonable request., (Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Published
2021
Full Text
View/download PDF

9. Immune-related Adverse Events of Pembrolizumab in a Large Real-world Cohort of Patients With NSCLC With a PD-L1 Expression ≥ 50% and Their Relationship With Clinical Outcomes.

Author

Cortellini A, Friedlaender A, Banna GL, Porzio G, Bersanelli M, Cappuzzo F, Aerts JGJV, Giusti R, Bria E, Cortinovis D, Grossi F, Migliorino MR, Galetta D, Passiglia F, Berardi R, Mazzoni F, Di Noia V, Signorelli D, Tuzi A, Gelibter A, Marchetti P, Macerelli M, Rastelli F, Chiari R, Rocco D, Inno A, Di Marino P, Mansueto G, Zoratto F, Santoni M, Tudini M, Ghidini M, Filetti M, Catino A, Pizzutilo P, Sala L, Occhipinti MA, Citarella F, Russano M, Torniai M, Cantini L, Follador A, Sforza V, Nigro O, Ferrara MG, D'Argento E, Leonetti A, Pettoruti L, Antonuzzo L, Scodes S, Landi L, Guaitoli G, Baldessari C, Bertolini F, Della Gravara L, Dal Bello MG, Belderbos RA, De Filippis M, Cecchi C, Ricciardi S, Donisi C, De Toma A, Proto C, Addeo A, Cantale O, Ricciuti B, Genova C, Morabito A, Santini D, Ficorella C, and Cannita K

Subjects
Adult, Aged, Aged, 80 and over, Carcinoma, Non-Small-Cell Lung metabolism, Carcinoma, Non-Small-Cell Lung pathology, Carcinoma, Squamous Cell metabolism, Carcinoma, Squamous Cell pathology, Drug-Related Side Effects and Adverse Reactions etiology, Female, Follow-Up Studies, Humans, Lung Neoplasms metabolism, Lung Neoplasms pathology, Male, Middle Aged, Prognosis, Retrospective Studies, Survival Rate, Antibodies, Monoclonal, Humanized adverse effects, Antineoplastic Agents, Immunological adverse effects, B7-H1 Antigen metabolism, Carcinoma, Non-Small-Cell Lung drug therapy, Carcinoma, Squamous Cell drug therapy, Drug-Related Side Effects and Adverse Reactions pathology, Lung Neoplasms drug therapy
Abstract

Background: The role of immune-related adverse events (irAEs), as a surrogate predictor of the efficacy of checkpoint inhibitors, has not yet been described in the setting of first-line, single-agent pembrolizumab for patients with metastatic non-small-cell lung-cancer (NSCLC) with a programmed death-ligand 1 (PD-L1) expression of ≥ 50%., Patients and Methods: We previously conducted a multicenter retrospective analysis in patients with treatment-naive metastatic NSCLC and a PD-L1 expression of ≥ 50% receiving first-line pembrolizumab. Here, we report the results of the irAE analysis and the potential correlation between irAEs and clinical outcomes., Results: A total of 1010 patients were included in this analysis; after a 6-week landmark selection, 877 (86.8%) patients were included in the efficacy analysis. Any grade irAEs (P < .0001), grade 3/4 irAEs (P = .0025), leading to discontinuation irAEs (P = .0144), multiple-site and single-site irAEs (P < .0001), cutaneous irAEs (P = .0001), endocrine irAEs (P = .0227), pulmonary irAEs (P = .0479), and rheumatologic irAEs (P = .0018) were significantly related to a higher objective response rate. Any grade irAEs (P < .0001), single-site irAEs (P < .0001), multiple-site irAEs (P = .0005), cutaneous irAEs (P = .0042), endocrine irAEs (P < .0001), gastrointestinal irAEs (P = .0391), and rheumatologic irAEs (P = .0086) were significantly related to progression-free survival. Any grade irAEs (P < .0001), single-site irAEs (P < .0001), multiple-site irAEs (P = .0003), cutaneous irAEs (P = .0002), endocrine irAEs (P = .0001), and rheumatologic irAEs (P = .0214) were significantly related to overall survival., Conclusions: This study confirms the feasibility and the safety of first-line, single-agent pembrolizumab, in a large, real-world cohort of patients with NSCLC with PD-L1 expression ≥ 50%. The occurrence of irAEs may be a surrogate of clinical activity and improved outcomes in this setting., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Published
2020
Full Text
View/download PDF

10. Anti-PD1 antibodies in patients aged ≥ 75 years with metastatic melanoma: A retrospective multicentre study.

Author

Ridolfi L, De Rosa F, Petracci E, Tanda ET, Marra E, Pigozzo J, Marconcini R, Guida M, Cappellini GCA, Gallizzi G, Occelli M, Pala L, Gambale E, Bersanelli M, Galdo G, Cortellini A, Morgese F, Zoratto F, Stucci LS, Strippoli S, and Guidoboni M

Subjects
Aged, Aged, 80 and over, Female, Humans, Male, Nivolumab adverse effects, Prognosis, Retrospective Studies, Antibodies, Monoclonal, Humanized therapeutic use, Melanoma drug therapy
Abstract

Background: Advanced age is associated with comorbidities and immune system impairment, which may influence the efficacy and tolerability of immune checkpoint inhibitors. There is evidence that anti-PD1 antibodies in advanced melanoma are equally effective in patients >65 years. However, data on patients >75 years are lacking as co-morbidities and logistics often exclude them from clinical trials., Methods: We retrospectively reviewed the clinical records of older patients with advanced melanoma undergoing any-line treatment with an anti-PD1 (nivolumab/pembrolizumab) to investigate its clinical effectiveness and toxicity in a real-life setting. Clinical response was assessed using RECIST criteria and toxicity was evaluated according to CTCAE 4.0. Progression-free survival (PFS) and overall survival (OS) were estimated with the Kaplan-Meier method and the Cox model was used to assess potential prognostic factors., Results: 174 patients were considered; 59.2% males, median age 79 years (range 75-93). The majority had a performance status of 0 and normal lactate dehydrogenase (LDH) levels (55.2% and 52.4%, respectively). 69.1% had multiple co-morbidities. 56.9% received nivolumab. 36.7% of cases showed an objective response and the disease control rate was 56.3%. Median OS was 17.2 months [95% CI: 8.87-not reached] and a better prognosis was observed for patients with normal LDH (p < .001) and lower performance status (p < .001). Treatment was well tolerated, only 11 patients experiencing severe (grade 3/4) toxicity. There were no treatment-related deaths. Adverse events were managed with corticosteroids and additional immunosuppressive agents were unnecessary., Conclusions: Anti-PD1 antibodies appear effective and well tolerated in older patients with advanced melanoma., Competing Interests: Declaration of competing interest None to declare., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Published
2020
Full Text
View/download PDF

11. Correlations Between the Immune-related Adverse Events Spectrum and Efficacy of Anti-PD1 Immunotherapy in NSCLC Patients.

Author

Cortellini A, Chiari R, Ricciuti B, Metro G, Perrone F, Tiseo M, Bersanelli M, Bordi P, Santini D, Giusti R, Grassadonia A, Di Marino P, Tinari N, De Tursi M, Zoratto F, Veltri E, Malorgio F, Garufi C, Russano M, Anesi C, Zeppola T, Filetti M, Marchetti P, Berardi R, Rinaldi S, Tudini M, Silva RR, Pireddu A, Atzori F, Iacono D, Migliorino MR, Porzio G, Cannita K, Ficorella C, and Buti S

Subjects
Adult, Aged, Aged, 80 and over, Antibodies, Monoclonal, Humanized adverse effects, Carcinoma, Non-Small-Cell Lung epidemiology, Carcinoma, Non-Small-Cell Lung mortality, Female, Humans, Immune System Diseases etiology, Immunotherapy adverse effects, Italy epidemiology, Lung Neoplasms epidemiology, Lung Neoplasms mortality, Male, Middle Aged, Nivolumab adverse effects, Programmed Cell Death 1 Receptor antagonists & inhibitors, Retrospective Studies, Survival Analysis, Treatment Outcome, Young Adult, Antibodies, Monoclonal, Humanized therapeutic use, Carcinoma, Non-Small-Cell Lung drug therapy, Drug-Related Side Effects and Adverse Reactions epidemiology, Immune System Diseases epidemiology, Immunotherapy methods, Lung Neoplasms drug therapy, Nivolumab therapeutic use
Abstract

Background: Immune-related adverse events (irAEs) developed during immunotherapy with anti-PD-1 agents, could be a predictive surrogate marker of clinical benefit in patients with advanced non-small-cell lung cancer (NSCLC)., Methods: Patients with NSCLC, treated with anti-PD-1 agents, were retrospectively evaluated. Univariate and multivariate analyses were performed to evaluate the relationships between types of irAEs (differentiated according to system/organ involved and to single-site/multiple-site), overall response rate (ORR), progression-free survival (PFS) and overall survival (OS). We further performed a 6-week landmark analysis., Results: A total of 559 patients were enrolled; 231 patients (41.3%) developed irAEs of any grade and 50 patients (8.9%) G3/G4 events; 191 of them (82.6%) developed "single-site" irAEs and 40 (17.4%) "multiple-site" irAEs. At multivariate analysis, higher ORR was related to irAEs of any grade (P < .0001), "single-site" irAEs (P < .0001), endocrine (P = .0043) and skin irAEs (P = .0005). Longer PFS was related to irAEs of any grade (P < .0001), "single-site" irAEs (P < .0001), "multiple-site" irAEs (P = .0374), endocrine irAEs (P = .0084) and skin irAEs (P = .0001). Longer OS was related to irAEs of any grade (P < .0001), "single-site" irAEs (P < .0001), endocrine irAEs (P = .0044), gastrointestinal irAEs (P = .0437), skin irAEs (P = .0006), and others irAEs (P = .0378). At the 6-week landmark analysis, irAEs of any grade was confirmed an independent predictor of higher ORR, longer PFS, and longer OS., Conclusion: Our study confirmed that irAEs are concordantly related to higher ORR, longer PFS, and longer OS with anti-PD-1 immunotherapy in patients with NSCLC., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Published
2019
Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results