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8 results on '"Biagio Ricciuti"'

1. Additional impact of genetic ancestry over race/ethnicity to prevalence of KRAS mutations and allele-specific subtypes in non-small cell lung cancer

Author

Xinan Wang, Kangcheng Hou, Biagio Ricciuti, Joao V. Alessi, Xihao Li, Federica Pecci, Rounak Dey, Jia Luo, Mark M. Awad, Alexander Gusev, Xihong Lin, Bruce E. Johnson, and David C. Christiani

Subjects
non-small cell lung cancer (NSCLC), KRAS, somatic mutation, biomarker, race/ethnicity, genetic ancestry, Genetics, QH426-470
Abstract

Summary: The KRAS mutation is the most common oncogenic driver in patients with non-small cell lung cancer (NSCLC). However, a detailed understanding of how self-reported race and/or ethnicity (SIRE), genetically inferred ancestry (GIA), and their interaction affect KRAS mutation is largely unknown. Here, we investigated the associations between SIRE, quantitative GIA, and KRAS mutation and its allele-specific subtypes in a multi-ethnic cohort of 3,918 patients from the Boston Lung Cancer Survival cohort and the Chinese OrigiMed cohort with an independent validation cohort of 1,450 patients with NSCLC. This comprehensive analysis included detailed covariates such as age at diagnosis, sex, clinical stage, cancer histology, and smoking status. We report that SIRE is significantly associated with KRAS mutations, modified by sex, with SIRE-Asian patients showing lower rates of KRAS mutation, transversion substitution, and the allele-specific subtype KRASG12C compared to SIRE-White patients after adjusting for potential confounders. Moreover, GIA was found to correlate with KRAS mutations, where patients with a higher proportion of European ancestry had an increased risk of KRAS mutations, especially more transition substitutions and KRASG12D. Notably, among SIRE-White patients, an increase in European ancestry was linked to a higher likelihood of KRAS mutations, whereas an increase in admixed American ancestry was associated with a reduced likelihood, suggesting that quantitative GIA offers additional information beyond SIRE. The association of SIRE, GIA, and their interplay with KRAS driver mutations in NSCLC highlights the importance of incorporating both into population-based cancer research, aiming to refine clinical decision-making processes and mitigate health disparities.

Published
2024
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3. Association Between Immune-Related Adverse Events and Clinical Outcomes to Programmed Cell Death Protein 1/Programmed Death-Ligand 1 Blockade in SCLC

Author

Biagio Ricciuti, MD, Abdul Rafeh Naqash, MD, Jarushka Naidoo, MD, Kartik Sehgal, MD, Adam Miller, MD, Kenneth Kehl, MD, MPH, Deepti Venkatraman, MPH, Jacob Sands, MD, Giuseppe Lamberti, MD, Gonzalo Recondo, MD, PhD, Jiajia Zhang, MD, Shravanti Macherla, MD, Sameer Baig, MD, Paul Walker, MD, Deepa Rangachari, MD, Justin F. Gainor, MD, Daniel B. Costa, MD, Naiyer Rizvi, MD, Lynette M. Sholl, MD, Mizuki Nishino, MD, MPH, Brian Henick, MD, Anna F. Farago, MD, PhD, and Mark M. Awad, MD, PhD

Subjects
SCLC, irAEs, PD-(L)1, CTLA-4, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

Introduction: The development of immune-related adverse events (irAEs) has been associated with improved efficacy of immune checkpoint inhibitors in patients with urothelial cancer, melanoma, and NSCLC. Whether this association exists in patients with SCLC is currently unknown. Methods: We conducted a multicenter retrospective study to evaluate the relationship between irAEs and immunotherapy efficacy in SCLC. To account for the lead-time bias resulting from the time-dependent nature of irAEs, the development of irAEs was considered as a time-varying covariate in univariate and multivariate Cox proportional hazard models. Results: Of the 183 patients treated with immunotherapy, 73 (39.9%) experienced at least one irAE. A total of 42 patients (22.9%) had grade 1 to 2 irAEs, whereas 31 patients (16.9%) had grade 3 to 4 irAEs. The median time of onset to the first irAE was 24 days (interquartile range: 14–55). The baseline clinicopathologic features were well-balanced between patients with and without irAEs. At a median follow-up of 24 months (95% confidence interval [CI]: 17.0–31.6), the median progression-free survival was significantly longer in the irAE group than the non-irAE group (3.8 versus 1.3 mo, p < 0.0001). The median overall survival was also significantly longer among patients with irAEs than patients without irAEs (13.8 versus 2.9 mo, p < 0.0001). When analyzed as a time-varying covariate, the development of irAEs was associated with a significant improvement in progression-free survival (hazard ratio: 0.44 [95% CI: 0.29–0.66], p < 0.001) and overall survival (hazard ratio: 0.47 [95% CI: 0.32–0.71], p < 0.001) in multivariate models. Conclusions: The development of irAEs is associated with improved clinical outcomes for immunotherapy in patients with advanced SCLC.

Published
2020
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4. Reply to Cortellini A

Author

Biagio Ricciuti, MD and Mark M. Awad, MD, PhD

Subjects
Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Published
2020
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5. 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

Raffaele Giusti, Giorgia Guaitoli, Mario Occhipinti, Diego Cortinovis, Ornella Cantale, Luca Cantini, Cinzia Baldessari, Alessio Cortellini, Francesco Grossi, Linda Pettoruti, Vincenzo Sforza, Giovanni Mansueto, Francesco Passiglia, Francesca Mazzoni, Lorenza Landi, Alain Gelibter, Melissa Bersanelli, Daniele Santini, Paolo Marchetti, Alessandro Morabito, Alessandro Leonetti, Marianna Tudini, Serena Ricciardi, Fabrizio Citarella, Ettore D'Argento, Francesca Rastelli, Matteo Santoni, Vincenzo Di Noia, Giampiero Porzio, Robert A. Belderbos, Claudia Proto, Simona Scodes, Marianna Macerelli, Marco Filetti, Joachim G.J.V. Aerts, Diego Signorelli, Luigi Della Gravara, Carlo Genova, Danilo Rocco, Lorenzo Antonuzzo, Alessandro Tuzi, Cristina Cecchi, Luca Sala, Corrado Ficorella, Marco De Filippis, Giuseppe Luigi Banna, Alessandro Inno, Mariangela Torniai, Pamela Pizzutilo, Emilio Bria, Maria Giovanna Dal Bello, Domenico Galetta, Federico Cappuzzo, Federica Bertolini, Rossana Berardi, Maria Rita Migliorino, Miriam Grazia Ferrara, Clelia Donisi, Rita Chiari, Alessandro De Toma, Olga Nigro, Michele Ghidini, Annamaria Catino, Alfredo Addeo, Federica Zoratto, Alessandro Follador, Pietro Di Marino, Alex Friedlaender, Marco Russano, Biagio Ricciuti, Katia Cannita, and Pulmonary Medicine

Subjects
0301 basic medicine, Pulmonary and Respiratory Medicine, Oncology, Adult, Male, PD-L1, Cancer Research, medicine.medical_specialty, Lung Neoplasms, Drug-Related Side Effects and Adverse Reactions, First line, irAEs, NSCLC, Pembrolizumab, Immune checkpoint inhibitors, Antibodies, Monoclonal, Humanized, B7-H1 Antigen, 03 medical and health sciences, 0302 clinical medicine, Immune system, Antineoplastic Agents, Immunological, Internal medicine, Carcinoma, Non-Small-Cell Lung, medicine, Humans, Adverse effect, Lung cancer, Aged, Retrospective Studies, Aged, 80 and over, biology, business.industry, Middle Aged, medicine.disease, Prognosis, Survival Rate, 030104 developmental biology, 030220 oncology & carcinogenesis, Cohort, biology.protein, Carcinoma, Squamous Cell, Pd l1 expression, Female, business, Follow-Up Studies
Abstract

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%.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.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.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

6. Antibiotic-exposed patients with non-small-cell lung cancer preserve efficacy outcomes following first-line chemo-immunotherapy

Author

David J. Pinato, Francesco Facchinetti, Alessio Cortellini, Jose Carlos Benitez, Joao Victor Machado Alessi, Karla A. Lee, Paola Cravero, I. Sullivan, T. Gorria, A. Barba, F. Aboubakar Nana, Mark M. Awad, N. Hussain, Delphine Hoton, James Clark, Anita Bolina, L. Mezquita, Deepti Venkatraman, Margarita Majem, F.G. Dall'Olio, Diego Ottaviani, A. Piedra, Victor Vaz, Benjamin Besse, Giuseppe Lamberti, and Biagio Ricciuti

Subjects
Oncology, medicine.medical_specialty, Lung Neoplasms, predictive factors, medicine.drug_class, medicine.medical_treatment, Immune checkpoint inhibitors, First line, Antibiotics, Pembrolizumab, chemotherapy, antibiotics, immune checkpoint inhibitors, Carcinoma, Non-Small-Cell Lung, Internal medicine, medicine, Humans, Lung cancer, Chemo immunotherapy, Chemotherapy, business.industry, Hematology, medicine.disease, Anti-Bacterial Agents, Treatment Outcome, non-small-cell lung cancer, Immunotherapy, Non small cell, pembrolizumab, business
Abstract

Background: Prior antibiotic therapy (pATB) is known to impair efficacy of single-agent immune checkpoint inhibitors (ICIs), potentially through the induction of gut dysbiosis. Whether ATB also affects outcomes to chemo-immunotherapy combinations is still unknown. Patients and methods: In this international multicentre study, we evaluated the association between pATB, concurrent ATB (cATB) and overall survival (OS), progression-free survival (PFS) and objective response rate (ORR) in patients with non-small-cell lung cancer (NSCLC) treated with first-line chemo-immunotherapy at eight referral institutions. Results: Among 302 patients with stage IV NSCLC, 216 (71.5%) and 61 (20.2%) patients were former and current smokers, respectively. Programmed death-ligand 1 tumour expression in assessable patients (274, 90.7%) was >= 50% in 76 (25.2%), 1%-49% in 84 (27.9%) and = 7 versus

Published
2021

7. Association Between Immune-Related Adverse Events and Clinical Outcomes to Programmed Cell Death Protein 1/Programmed Death-Ligand 1 Blockade in SCLC

Author

Justin F. Gainor, Jiajia Zhang, Anna F. Farago, Biagio Ricciuti, Sameer Baig, Mizuki Nishino, Adam Miller, Paul R. Walker, Kartik Sehgal, Daniel B. Costa, Mark M. Awad, Jacob Sands, Deepa Rangachari, Deepti Venkatraman, Brian S. Henick, Gonzalo Recondo, Naiyer A. Rizvi, Shravanti Macherla, Giuseppe Lamberti, Abdul Rafeh Naqash, Jarushka Naidoo, Lynette M. Sholl, Kenneth L. Kehl, Ricciuti B., Naqash A.R., Naidoo J., Sehgal K., Miller A., Kehl K., Venkatraman D., Sands J., Lamberti G., Recondo G., Zhang J., Macherla S., Baig S., Walker P., Rangachari D., Gainor J.F., Costa D.B., Rizvi N., Sholl L.M., Nishino M., Henick B., Farago A.F., and Awad M.M.

Subjects
Pulmonary and Respiratory Medicine, Oncology, medicine.medical_specialty, medicine.medical_treatment, PD-(L)1, lcsh:RC254-282, Interquartile range, Internal medicine, irAE, medicine, Adverse effect, business.industry, Melanoma, SCLC, Retrospective cohort study, Immunotherapy, medicine.disease, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, Confidence interval, Blockade, CTLA-4, irAEs, Original Article, business
Abstract

Introduction: The development of immune-related adverse events (irAEs) has been associated with improved efficacy of immune checkpoint inhibitors in patients with urothelial cancer, melanoma, and NSCLC. Whether this association exists in patients with SCLC is currently unknown. Methods: We conducted a multicenter retrospective study to evaluate the relationship between irAEs and immunotherapy efficacy in SCLC. To account for the lead-time bias resulting from the time-dependent nature of irAEs, the development of irAEs was considered as a time-varying covariate in univariate and multivariate Cox proportional hazard models. Results: Of the 183 patients treated with immunotherapy, 73 (39.9%) experienced at least one irAE. A total of 42 patients (22.9%) had grade 1 to 2 irAEs, whereas 31 patients (16.9%) had grade 3 to 4 irAEs. The median time of onset to the first irAE was 24 days (interquartile range: 14–55). The baseline clinicopathologic features were well-balanced between patients with and without irAEs. At a median follow-up of 24 months (95% confidence interval [CI]: 17.0–31.6), the median progression-free survival was significantly longer in the irAE group than the non-irAE group (3.8 versus 1.3 mo, p < 0.0001). The median overall survival was also significantly longer among patients with irAEs than patients without irAEs (13.8 versus 2.9 mo, p < 0.0001). When analyzed as a time-varying covariate, the development of irAEs was associated with a significant improvement in progression-free survival (hazard ratio: 0.44 [95% CI: 0.29–0.66], p < 0.001) and overall survival (hazard ratio: 0.47 [95% CI: 0.32–0.71], p < 0.001) in multivariate models. Conclusions: The development of irAEs is associated with improved clinical outcomes for immunotherapy in patients with advanced SCLC.

Published
2020

8. Leptomeningeal Response to Capmatinib After Progression on Crizotinib in a Patient With MET Exon 14–Mutant NSCLC

Author

Mizuki Nishino, Nuno Vaz, Biagio Ricciuti, Kaitlin Morton, Dawn Drevers, Gianluca Diubaldi, Paola Cravero, Mark M. Awad, Rebecca E. Rivenburgh, and Sarah E. Clifford

Subjects
Pulmonary and Respiratory Medicine, Capmatinib, Crizotinib, business.industry, Mutant, Case Report, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, lcsh:RC254-282, Exon, Oncology, Cancer research, Medicine, business, medicine.drug
Published
2020

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