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1. Sodium levels and immunotherapy efficacy in mRCC patients with bone metastases: sub analysis of Meet-Uro 15 study

Author

Martina Catalano, Sara Elena Rebuzzi, Marco Maruzzo, Ugo De Giorgi, Sebastiano Buti, Luca Galli, Giuseppe Fornarini, Paolo Andrea Zucali, Melanie Claps, Silvia Chiellino, Ilaria Zampiva, Stefania Pipitone, Riccardo Ricotta, Mariella Sorarù, Veronica Mollica, Marianna Tudini, Lucia Fratino, Veronica Prati, Orazio Caffo, Francesco Atzori, Franco Morelli, Giuseppe Prati, Franco Nolè, Francesca Vignani, Alessia Cavo, Marilena Di Napoli, Andrea Malgeri, Emanuele Naglieri, Alessio Signori, Giuseppe Luigi Banna, Pasquale Rescigno, Linda Cerbone, Lorenzo Antonuzzo, and Giandomenico Roviello

Subjects
renal cell carcinoma, bone metastases, immunotherapy, sodium levels, efficacy outcomes, Immunologic diseases. Allergy, RC581-607
Abstract

BackgroundImmune-checkpoint inhibitors (ICIs) have significantly improved metastatic renal cell carcinoma (mRCC) prognosis, although their efficacy in patients with bone metastases (BMs) remains poorly understood. We investigated the prognostic role of natremia in pretreated RCC patients with BMs receiving immunotherapy.Materials and methodsThis retrospective multicenter study included RCC patients with BMs receiving nivolumab as second-line therapy or beyond. Inclusion criteria involved baseline sodium levels (pre-ICI) and sodium levels after 4 weeks of nivolumab initiation (post-ICI). The population was divided into two groups based on the median value, and response rates, progression-free survival (PFS), and overall survival (OS) were assessed.ResultsAmong 120 eligible patients, those with pre-treatment sodium levels ≥140 mEq/L showed longer OS (18.7 vs. 12.0 months, p=0.04). Pre-treatment sodium levels ≥140 mEq/L were associated with better OS compared to levels

Published
2024
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2. Time to strategy failure and treatment beyond progression in pretreated metastatic renal cell carcinoma patients receiving nivolumab: post-hoc analysis of the Meet-URO 15 study

Author

Veronica Murianni, Alessio Signori, Sebastiano Buti, Sara Elena Rebuzzi, Davide Bimbatti, Ugo De Giorgi, Silvia Chiellino, Luca Galli, Paolo Andrea Zucali, Cristina Masini, Emanuele Naglieri, Giuseppe Procopio, Michele Milella, Lucia Fratino, Cinzia Baldessari, Riccardo Ricotta, Veronica Mollica, Mariella Sorarù, Marianna Tudini, Veronica Prati, Andrea Malgeri, Francesco Atzori, Marilena Di Napoli, Orazio Caffo, Massimiliano Spada, Franco Morelli, Giuseppe Prati, Franco Nolè, Francesca Vignani, Alessia Cavo, Helga Lipari, Giandomenico Roviello, Fabio Catalano, Alessandra Damassi, Malvina Cremante, Pasquale Rescigno, Giuseppe Fornarini, and Giuseppe Luigi Banna

Subjects
metastatic renal cell carcinoma, immunotherapy, immune checkpoint inhibitors, nivolumab, treatment beyond progression, time to strategy failure, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

BackgroundImmunotherapies exhibit peculiar cancer response patterns in contrast to chemotherapy and targeted therapy. Some patients experience disease response after initial progression or durable responses after treatment interruption. In clinical practice, immune checkpoint inhibitors may be continued after radiological progression if clinical benefit is observed. As a result, estimating progression-free survival (PFS) based on the first disease progression may not accurately reflect the actual benefit of immunotherapy.MethodsThe Meet-URO 15 study was a multicenter retrospective analysis of 571 pretreated metastatic renal cell carcinoma (mRCC) patients receiving nivolumab. Time to strategy failure (TSF) was defined as the interval from the start of immunotherapy to definitive disease progression or death. This post-hoc analysis compared TSF to PFS and assess the response and survival outcomes between patients treatated beyond progression (TBP) and non-TBP. Moreover, we evaluated the prognostic accuracy of the Meet-URO score versus the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) score based on TSF and PFS.ResultsOverall, 571 mRCC patients were included in the analysis. Median TSF was 8.6 months (95% CI: 7.0 – 10.1), while mPFS was 7.0 months (95% CI: 5.7 – 8.5). TBP patients (N = 93) had significantly longer TSF (16.3 vs 5.5 months; p < 0.001) and overall survival (OS) (34.8 vs 17.9 months; p < 0.001) but similar PFS compared to non-TBP patients. In TBP patients, a median delay of 9.6 months (range: 6.7-16.3) from the first to the definitive disease progression was observed, whereas non-TBP patients had overlapped median TSF and PFS (5.5 months). Moreover, TBP patients had a trend toward a higher overall response rate (33.3% vs 24.3%; p = 0.075) and disease control rate (61.3% vs 55.5%; p = 0.31). Finally, in the whole population the Meet-URO score outperformed the IMDC score in predicting both TSF (c-index: 0.63 vs 0.59) and PFS (0.62 vs 0.59).ConclusionWe found a 2-month difference between mTSF and mPFS in mRCC patients receiving nivolumab. However, TBP patients had better outcomes, including significantly longer TSF and OS than non-TBP patients. The Meet-URO score is a reliable predictor of TSF and PFS.

Published
2024
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3. Early fatigue in cancer patients receiving PD-1/PD-L1 checkpoint inhibitors: an insight from clinical practice

Author

Alessio Cortellini, Maria G. Vitale, Federica De Galitiis, Francesca R. Di Pietro, Rossana Berardi, Mariangela Torniai, Michele De Tursi, Antonino Grassadonia, Pietro Di Marino, Daniele Santini, Tea Zeppola, Cecilia Anesi, Alain Gelibter, Mario Alberto Occhipinti, Andrea Botticelli, Paolo Marchetti, Francesca Rastelli, Federica Pergolesi, Marianna Tudini, Rosa Rita Silva, Domenico Mallardo, Vito Vanella, Corrado Ficorella, Giampiero Porzio, and Paolo A. Ascierto

Subjects
Fatigue, Cancer, Immune-related adverse events, IL-6, PD-1/PD-L1 inhibitors, Immunotherapy, Medicine
Abstract

Abstract Background Fatigue was reported as the most common any-grade adverse event (18.3%), and the most common grade 3 or higher immune-related adverse event (irAE) (0.89%) in patients receiving PD-1/PD-L1 checkpoint inhibitors in clinical trial. Methods The aim of this retrospective multicenter study was to evaluate the correlations between “early ir-fatigue”, “delayed ir-fatigue”, and clinical outcomes in cancer patients receiving PD-1/PD-L1 inhibitors in clinical practice. Results 517 patients were evaluated. After the 12-weeks landmark selection, 386 (74.7%) patients were eligible for the clinical outcomes analysis. 40.4% were NSCLC, 42.2% were melanoma, 15.3% renal cell carcinoma and 2.1% other malignancies. 76 patients (19.7%) experienced early ir-fatigue (within 1 month from treatment commencement), while 150 patients (38.9%) experienced delayed ir-fatigue. Early ir-fatigue was significantly related to shortened PFS (HR = 2.29 [95% CI 1.62–3.22], p

Published
2019
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4. A multicenter study of body mass index in cancer patients treated with anti-PD-1/PD-L1 immune checkpoint inhibitors: when overweight becomes favorable

Author

Alessio Cortellini, Melissa Bersanelli, Sebastiano Buti, Katia Cannita, Daniele Santini, Fabiana Perrone, Raffaele Giusti, Marcello Tiseo, Maria Michiara, Pietro Di Marino, Nicola Tinari, Michele De Tursi, Federica Zoratto, Enzo Veltri, Riccardo Marconcini, Francesco Malorgio, Marco Russano, Cecilia Anesi, Tea Zeppola, Marco Filetti, Paolo Marchetti, Andrea Botticelli, Gian Carlo Antonini Cappellini, Federica De Galitiis, Maria Giuseppa Vitale, Francesca Rastelli, Federica Pergolesi, Rossana Berardi, Silvia Rinaldi, Marianna Tudini, Rosa Rita Silva, Annagrazia Pireddu, Francesco Atzori, Rita Chiari, Biagio Ricciuti, Andrea De Giglio, Daniela Iacono, Alain Gelibter, Mario Alberto Occhipinti, Alessandro Parisi, Giampiero Porzio, Maria Concetta Fargnoli, Paolo Antonio Ascierto, Corrado Ficorella, and Clara Natoli

Subjects
BMI, Anti-PD-1/PD-L1, Overweight, Obesity, Cancer, Immunotherapy, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

Abstract Background Recent evidence suggested a potential correlation between overweight and the efficacy of immune checkpoint inhibitors (ICIs) in cancer patients. Patients and methods We conducted a retrospective study of advanced cancer patients consecutively treated with anti-PD-1/PD-L1 inhibitors, in order to compare clinical outcomes according to baseline BMI levels as primary analysis. Based on their BMI, patients were categorized into overweight/obese (≥ 25) and non-overweight (

Published
2019
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5. Evaluating the role of FAMIly history of cancer and diagnosis of multiple neoplasms in cancer patients receiving PD-1/PD-L1 checkpoint inhibitors: the multicenter FAMI-L1 study

Author

Alessio Cortellini, Sebastiano Buti, Melissa Bersanelli, Raffaele Giusti, Fabiana Perrone, Pietro Di Marino, Nicola Tinari, Michele De Tursi, Antonino Grassadonia, Katia Cannita, Alessandra Tessitore, Federica Zoratto, Enzo Veltri, Francesco Malorgio, Marco Russano, Cecilia Anesi, Tea Zeppola, Marco Filetti, Paolo Marchetti, Andrea Botticelli, Gian Carlo Antonini Cappellini, Federica De Galitiis, Maria Giuseppa Vitale, Francesca Rastelli, Federica Pergolesi, Rossana Berardi, Silvia Rinaldi, Marianna Tudini, Rosa Rita Silva, Annagrazia Pireddu, Francesco Atzori, Daniela Iacono, Maria Rita Migliorino, Alain Gelibter, Mario Alberto Occhipinti, Francesco Martella, Alessandro Inno, Stefania Gori, Sergio Bracarda, Cristina Zannori, Claudia Mosillo, Alessandro Parisi, Giampiero Porzio, Domenico Mallardo, Maria Concetta Fargnoli, Marcello Tiseo, Daniele Santini, Paolo A Ascierto, and Corrado Ficorella

Subjects
family history of cancer, multiple neoplasms, ddr genes, immune checkpoint inhibitors, immunotherapy, pd-1, Immunologic diseases. Allergy, RC581-607, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

Background: We investigate the role of family history of cancer (FHC) and diagnosis of metachronous and/or synchronous multiple neoplasms (MN), during anti-PD-1/PD-L1 immunotherapy. Design: This was a multicenter retrospective study of advanced cancer patients treated with anti-PD-1/PD-L1 immunotherapy. FHC was collected in lineal and collateral lines, and patients were categorized as follows: FHC-high (in case of cancer diagnoses in both the lineal and collateral family lines), FHC-low (in case of cancer diagnoses in only one family line), and FHC-negative. Patients were also categorized according to the diagnosis of MN as follows: MN-high (>2 malignancies), MN-low (two malignancies), and MN-negative. Objective response rate (ORR), progression-free survival (PFS), overall survival (OS), and incidence of immune-related adverse events (irAEs) of any grade were evaluated. Results: 822 consecutive patients were evaluated. 458 patients (55.7%) were FHC-negative, 289 (35.2%) were FHC-low, and 75 (9.1%) FHC-high, respectively. 29 (3.5%) had a diagnosis of synchronous MN and 94 (11.4%) of metachronous MN. 108 (13.2%) and 15 (1.8%) patients were MN-low and MN-high, respectively. The median follow-up was 15.6 months. No significant differences were found regarding ORR among subgroups. FHC-high patients had a significantly longer PFS (hazard ratio [HR] = 0.69 [95% CI: 0.48–0.97], p = .0379) and OS (HR = 0.61 [95% CI: 0.39–0.93], p = .0210), when compared to FHC-negative patients. FHC-high was confirmed as an independent predictor for PFS and OS at multivariate analysis. No significant differences were found according to MN categories. FHC-high patients had a significantly higher incidence of irAEs of any grade, compared to FHC-negative patients (p = .0012). Conclusions: FHC-high patients seem to benefit more than FHC-negative patients from anti-PD-1/PD-L1 checkpoint inhibitors.

Published
2020
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7. Late immune-related adverse events in long-term responders to PD-1/PD-L1 checkpoint inhibitors: A multicentre study

Author

Alessandro Lazzarin, Rossana Berardi, Simone Scagnoli, Federica Cecchi, Sergio Bracarda, Luigia Stefania Stucci, Giampiero Porzio, Marco Russano, Pietro Di Marino, Marco Tucci, Francesco Spagnolo, Ilaria Vallini, V. Adamo, Biagio Ricciuti, Graziella Pinotti, Rita Chiari, Laura Pala, Melissa Bersanelli, Nicola Battelli, Alessandro Russo, Paolo Marchetti, Domenico Galetta, Olga Nigro, Fabio Conforti, Mariangela Torniai, Monica Giordano, Matteo B. Suter, Michele Ghidini, Corrado Ficorella, Erika Rijavec, Annamaria Catino, Alessio Cortellini, Michele De Tursi, Raffaele Giusti, Paola Bordi, Marco Filetti, Federica De Galitiis, Andrea De Giglio, Paola Queirolo, Alessandro Tuzi, Serena Macrini, Maria Concetta Fargnoli, Andrea Botticelli, Daniele Santini, Enrica Teresa Tanda, Pamela Pizzutilo, Elena Bolzacchini, Matteo Santoni, Rosa Rita Silva, Francesca Di Pietro, and Marianna Tudini

Subjects
Male, Oncology, 0301 basic medicine, Cancer Research, Immune checkpoint inhibitors, Pembrolizumab, Antineoplastic Agents, Immunological, 0302 clinical medicine, Immune-related adverse events, Neoplasms, Atezolizumab, Aged, 80 and over, biology, Middle Aged, Prognosis, Treatment period, Survival Rate, Nivolumab, 030220 oncology & carcinogenesis, Female, Immune checkpoint, Immunotherapy, Adult, medicine.medical_specialty, Drug-Related Side Effects and Adverse Reactions, Side effect, 03 medical and health sciences, Immune system, PD-L1, Internal medicine, medicine, Humans, In patient, Adverse effect, Survival rate, Aged, Retrospective Studies, business.industry, Disease progression, Retrospective cohort study, medicine.disease, 030104 developmental biology, Multicenter study, biology.protein, business, Adverse drug reaction, Follow-Up Studies
Abstract

Data on spectrum and grade of immune-related adverse events (irAEs) in long-term responders to immune checkpoint inhibitors (ICI) are lacking.We performed a retrospective multicenter study to characterized irAEs occurring after a 12-months minimum treatment period with PD-(L)1 ICIs in advanced cancer patients. IrAEs were categorized into “early” (≤12 months) and “late” (>12 months).From September 2013 to October 2019, 436 consecutive patients were evaluated. 223 experienced any grade early-irAEs (51.1%), while 132 experienced any grade late-irAEs (30.3%) (p < 0.0001). Among the latter, 29 (22%) experienced a recurrence of an early-irAEs, while 103 (78%) experienced de novo late-irAEs involving different system/organ. Among patients with late-irAEs, 21 experienced G3/G4 irAEs (4.8%). Median time to onset of early-irAEs was 3.4 months (95%CI: 2.8-4.2), while the median time to onset of late-irAEs was 16.6 months (95%CI: 15.8-17.6). Cumulative time-adjusted risk of disease progression according to both the early-irAEs (HR = 0.63 [95%CI: 0.30-1.29], p = 0.204) and late-irAEs occurrence revealed no statistically significant differences (HR = 0.75 [95%CI: 0.37-1.56], p = 0.452). Also the time-adjusted cumulative risk of death according to both early-irAEs (HR = 0.79 [95%CI: 0.34-1.86], p = 0.598) and late-irAEs (HR = 0.92 [95%CI: 0.49-1.74], p = 0.811) did not show statistically significant differences.Although less frequent than early-irAEs, late-irAEs are quite common in long responders to PD-(L)1 ICIs, and are different in terms of spectrum and grade. Time-adjusted analysis revealed that the cumulative risk of disease progression and death were not significantly reduced in patients who experienced late-irAEs.

Published
2020

8. Another side of the association between body mass index (BMI) and clinical outcomes of cancer patients receiving programmed cell death protein-1 (PD-1)/ Programmed cell death-ligand 1 (PD-L1) checkpoint inhibitors: A multicentre analysis of immune-related adverse events

Author

Giampiero Porzio, Michele De Tursi, Paolo A. Ascierto, Tea Zeppola, Marcello Tiseo, Daniele Santini, Sebastiano Buti, Francesca Rastelli, Sergio Bracarda, Rossana Berardi, Riccardo Marconcini, Clara Natoli, Andrea De Giglio, Rita Chiari, Cecilia Anesi, Marco Filetti, Federica Zoratto, Rosa Rita Silva, Melissa Bersanelli, Alessio Cortellini, Paolo Marchetti, Raffaele Giusti, Andrea Botticelli, Federica De Galitiis, Alain Gelibter, Corrado Ficorella, Claudia Mosillo, Vito Vanella, Maria Rita Migliorino, Marianna Tudini, Fabiana Perrone, Francesco Atzori, Marco Russano, Biagio Ricciuti, Katia Cannita, Silvia Rinaldi, Domenico Mallardo, and Maria Giuseppa Vitale

Subjects
Male, 0301 basic medicine, Oncology, Cancer Research, Programmed Cell Death 1 Receptor, Overweight, Severity of Illness Index, B7-H1 Antigen, Body Mass Index, Antineoplastic Agents, Immunological, 0302 clinical medicine, Risk Factors, Immune-related adverse events, Renal cell carcinoma, Neoplasms, 80 and over, Cancer, Aged, 80 and over, Incidence, Middle Aged, Immunological, BMI, Checkpoint inhibitors, Immunotherapy, Obesity, PD-1/PD-L1, 030220 oncology & carcinogenesis, Female, medicine.symptom, Underweight, Adult, medicine.medical_specialty, Drug-Related Side Effects and Adverse Reactions, Aged, Humans, Retrospective Studies, Young Adult, Antineoplastic Agents, 03 medical and health sciences, Internal medicine, medicine, Carcinoma, Adverse effect, business.industry, Retrospective cohort study, medicine.disease, 030104 developmental biology, business, Body mass index
Abstract

Several studies have found an association between higher body mass index (BMI) and improved clinical outcomes in cancer patients receiving programmed cell death protein-1 (PD-1)/programmed cell death-ligand 1 (PD-L1) checkpoint inhibitors. In a previous study, we found that overweight/obese patients were significantly more likely to experience any grade immune-related adverse events (irAEs) compared to non-overweight patients.We conducted a 'real-life', multi centre, retrospective observational study aimed at comparing the incidence of irAEs among cancer patients treated with PD-1/PD-L1 inhibitors according to baseline BMI.One thousand and seventy advanced cancer patients were evaluated. The median age was 68 years (range: 21-92), male/female ratio was 724/346. Primary tumours were: non-small-cell lung carcinoma (NSCLC) (653 patients), melanoma (233 patients), renal cell carcinoma (RCC) (152 patients) and others (29 patients). Median BMI was 25 (13.6-46.6); according to World Health Organisation (WHO) classification, 44 patients (4.1%) were defined as underweight, 480 patients (44.9%) as having a normal weight, 416 patients (38.9%) as overweight and 130 patients (12.1%) as obese. Higher BMI was significantly related to higher occurrence of any grade immune-related adverse events [irAEs] (p 0.0001), G3/G4 irAEs (p 0.0001) and irAEs leading to discontinuation (LTD) (p 0.0001). Overweight and obesity were confirmed predictors for irAEs of any grade at both univariate and multivariate analysis. The adjusted odds ratios (ORs) (compared to normal-weight) were 10.6; 95% confidence interval (95%CI): 7.5-14.9 for overweight, and 16.6 (95%CI: 10.3-26.7) for obese patients. Obesity was the only factor significantly related to a higher incidence of G3/G4 irAEs (OR = 11.9 [95%CI: 6.4-22.3], p 0.0001) and LTD irAEs (OR = 8.8 [95%CI: 4.3-18.2], p 0.0001). Overweight and obese patients experienced a significantly higher occurrence of cutaneous, endocrine, gastro-intestinal (GI), hepatic and 'others' irAEs, compared to normal-weight patients. Only obese patients experienced a significantly higher occurrence of pulmonary and rheumatic irAEs, compared to normal-weight patients.Considering the previously evidenced association between higher BMI and better outcome, the current finding about the relationship between BMI and irAEs occurrence can contribute to consideration of these findings as the upside of the downside, which underlies an 'immunogenic phenotype'.

Published
2020

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

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

10. Early fatigue in cancer patients receiving PD-1/PD-L1 checkpoint inhibitors: an insight from clinical practice

Author

Cecilia Anesi, Paolo Marchetti, Alessio Cortellini, Rossana Berardi, Mario Occhipinti, Marianna Tudini, Francesca Rastelli, Alain Gelibter, Andrea Botticelli, Rosa Rita Silva, Francesca Di Pietro, Paolo A. Ascierto, Giampiero Porzio, Mariangela Torniai, Daniele Santini, Federica De Galitiis, Corrado Ficorella, Federica Pergolesi, Pietro Di Marino, Maria Grazia Vitale, Vito Vanella, Domenico Mallardo, Michele De Tursi, Antonino Grassadonia, and Tea Zeppola

Subjects
Adult, Male, medicine.medical_specialty, Multivariate analysis, Programmed Cell Death 1 Receptor, lcsh:Medicine, Kaplan-Meier Estimate, General Biochemistry, Genetics and Molecular Biology, B7-H1 Antigen, Disease-Free Survival, Young Adult, Renal cell carcinoma, Immune-related adverse events, Internal medicine, Medicine, Humans, Practice Patterns, Physicians', Adverse effect, Fatigue, Aged, Cancer, Aged, 80 and over, IL-6, Performance status, business.industry, Melanoma, Research, lcsh:R, PD-1/PD-L1 inhibitors, General Medicine, Middle Aged, medicine.disease, Clinical trial, IL-6, PD-1/PD-L1 inhibitors, Immunotherapy, Multivariate Analysis, Population study, Female, business
Abstract

Background Fatigue was reported as the most common any-grade adverse event (18.3%), and the most common grade 3 or higher immune-related adverse event (irAE) (0.89%) in patients receiving PD-1/PD-L1 checkpoint inhibitors in clinical trial. Methods The aim of this retrospective multicenter study was to evaluate the correlations between “early ir-fatigue”, “delayed ir-fatigue”, and clinical outcomes in cancer patients receiving PD-1/PD-L1 inhibitors in clinical practice. Results 517 patients were evaluated. After the 12-weeks landmark selection, 386 (74.7%) patients were eligible for the clinical outcomes analysis. 40.4% were NSCLC, 42.2% were melanoma, 15.3% renal cell carcinoma and 2.1% other malignancies. 76 patients (19.7%) experienced early ir-fatigue (within 1 month from treatment commencement), while 150 patients (38.9%) experienced delayed ir-fatigue. Early ir-fatigue was significantly related to shortened PFS (HR = 2.29 [95% CI 1.62–3.22], p Conclusions Early ir-fatigue seems to be negative prognostic parameter, but to proper weight its role we must to consider the predominant role of performance status, which was related to early ir-fatigue in the study population.

Published
2019

11. Clinicopathologic correlates of pembrolizumab efficacy in patients with advanced NSCLC and a PD-L1 expression of ≥ 50%

Author

Alfredo Addeo, Vincenzo Di Noia, Robert A. Belderbos, Francesco Grossi, Joachim G.J.V. Aerts, Giampiero Porzio, Simona Scodes, Raffaele Giusti, Federico Cappuzzo, Giorgia Guaitoli, Diego Signorelli, Lorenzo Antonuzzo, Corrado Ficorella, Alessio Cortellini, Luigi Della Gravara, Alex Friedlaender, Giovanni Mansueto, Sebastiano Buti, Marcello Tiseo, Emilio Bria, Paolo Marchetti, Simona Carnio, Domenico Galetta, Alain Gelibter, Giada Targato, Ornella Cantale, Lorenza Landi, Diego Cortinovis, Maria Giovanna Dal Bello, Alessandro De Toma, Olga Nigro, Russano Marco, Luca Sala, Cinzia Baldessari, Michele De Tursi, Paola Bordi, Mariangela Torniai, Miriam Grazia Ferrara, Vincenzo Sforza, Marco Filetti, Maria Rita Migliorino, Claudia Proto, Giuseppe Luigi Banna, Alessandro Tuzi, Giulio Metro, Daniele Santini, Ettore D'Argento, Erika Rijavec, Stefania Gori, Biagio Ricciuti, Serena Ricciardi, Annamaria Catino, Rossana Berardi, Federica Zoratto, Marianna Macerelli, Paolo Bironzo, Luca Cantini, Fausto Barbieri, Francesca Mazzoni, Rita Chiari, Francesca Rastelli, Alessio Grieco, Alessandro Morabito, Fabrizio Citarella, Matteo Santoni, Carlo Genova, Danilo Rocco, Francesco Passiglia, Marianna Tudini, and Pamela Pizzutilo

Subjects
Oncology, medicine.medical_specialty, business.industry, First line, Pembrolizumab, medicine.disease, Metastasis, Clinical trial, Multicenter study, Internal medicine, Tobacco exposure, medicine, In patient, Pd l1 expression, business
Abstract

BackgroundSingle agent pembrolizumab represents the standard first line option for metastatic non-small-cell-lung-cancer (NSCLC) patients with a PD-L1 (programmed death-ligand 1) expression of ≥ 50%.MethodsWe conducted a multicenter study aimed at evaluating the clinicopathologic correlates of pembrolizumab efficacy in patients with treatment-naïve NSCLC and a PD-L1 TPS ≥ 50%.Results1026 consecutive patients were included. ECOG-PS ≥ 2 (p < 0.0001) and bone metastases (p = 0.0003) were confirmed to be independent predictors of a worse ORR. Former smokers (p = 0.0002), but not current smokers (p = 0.0532) were confirmed to have a significantly prolonged PFS compared to never smokers at multivariate analysis. ECOG-PS (p < 0.0001), bone metastases (p < 0.0001) and liver metastases (p < 0.0001) were also confirmed to be independent predictors of a worse PFS. Previous palliative RT was significantly related to a shortened OS (p = 0.0104), while previous non-palliative RT was significantly related to a prolonged OS (p = 0.0033). Former smokers (p = 0.0131), but not current smokers (p = 0.3433) were confirmed to have a significantly prolonged OS compared to never smokers. ECOG-PS (p < 0.0001), bone metastases (p < 0.0001) and liver metastases (p < 0.0001) were also confirmed to be independent predictors of a shortened OS. A PD-L1 expression of ≥ 90%, as assessed by recursive partitioning, was associated with significantly higher ORR (p = 0.0204), and longer and OS (p = 0.0346) at multivariable analysis.Conclusionspembrolizumab was effective in a large cohort of NSCLC patients treated outside of clinical trials. We confirmed that the absence of tobacco exposure, and the presence of bone and liver metastasis are associated with worse clinical outcomes to pembrolizumab. Increasing levels of PD-L1 expression may help identifying a subset of patients who derive a greater benefit from pembrolizumab monotherapy.

Published
2020

12. Evaluating the role of FAMIly history of cancer and diagnosis of multiple neoplasms in cancer patients receiving PD-1/PD-L1 checkpoint inhibitors. the multicenter FAMI-L1 study

Author

Fabiana Perrone, Rosa Rita Silva, Cristina Zannori, Paolo Marchetti, Francesco Atzori, Giampiero Porzio, Raffaele Giusti, Domenico Mallardo, Nicola Tinari, Enzo Veltri, Tea Zeppola, Federica De Galitiis, Marcello Tiseo, Alessio Cortellini, Cecilia Anesi, Claudia Mosillo, Alessandro Inno, Marianna Tudini, Stefania Gori, Alain Gelibter, Marco Filetti, Corrado Ficorella, Alessandra Tessitore, Melissa Bersanelli, Andrea Botticelli, Mario Occhipinti, Antonino Grassadonia, Marco Russano, Maria Giuseppa Vitale, Annagrazia Pireddu, Maria Concetta Fargnoli, Francesco Malorgio, Katia Cannita, Federica Pergolesi, Silvia Rinaldi, Michele De Tursi, Maria Rita Migliorino, Francesca Rastelli, Daniela Iacono, Gian Carlo Antonini Cappellini, Rossana Berardi, Pietro Di Marino, Alessandro Parisi, Sergio Bracarda, Paolo A. Ascierto, Daniele Santini, Sebastiano Buti, Federica Zoratto, and Francesco Martella

Subjects
0301 basic medicine, Oncology, multiple neoplasms, medicine.medical_specialty, Multivariate analysis, medicine.medical_treatment, Immunology, Programmed Cell Death 1 Receptor, ddr genes, B7-H1 Antigen, family history of cancer, immune checkpoint inhibitors, 03 medical and health sciences, 0302 clinical medicine, Antineoplastic Agents, Immunological, Internal medicine, Neoplasms, medicine, Immunology and Allergy, Humans, cardiovascular diseases, Family history, Adverse effect, RC254-282, Retrospective Studies, Original Research, business.industry, Incidence (epidemiology), Hazard ratio, pd-1, Cancer, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, Retrospective cohort study, Immunotherapy, RC581-607, medicine.disease, immunotherapy, 030104 developmental biology, 030220 oncology & carcinogenesis, Immunologic diseases. Allergy, business
Abstract

Background: We investigate the role of family history of cancer (FHC) and diagnosis of metachronous and/or synchronous multiple neoplasms (MN), during anti-PD-1/PD-L1 immunotherapy. Design: This was a multicenter retrospective study of advanced cancer patients treated with anti-PD-1/PD-L1 immunotherapy. FHC was collected in lineal and collateral lines, and patients were categorized as follows: FHC-high (in case of cancer diagnoses in both the lineal and collateral family lines), FHC-low (in case of cancer diagnoses in only one family line), and FHC-negative. Patients were also categorized according to the diagnosis of MN as follows: MN-high (>2 malignancies), MN-low (two malignancies), and MN-negative. Objective response rate (ORR), progression-free survival (PFS), overall survival (OS), and incidence of immune-related adverse events (irAEs) of any grade were evaluated. Results: 822 consecutive patients were evaluated. 458 patients (55.7%) were FHC-negative, 289 (35.2%) were FHC-low, and 75 (9.1%) FHC-high, respectively. 29 (3.5%) had a diagnosis of synchronous MN and 94 (11.4%) of metachronous MN. 108 (13.2%) and 15 (1.8%) patients were MN-low and MN-high, respectively. The median follow-up was 15.6 months. No significant differences were found regarding ORR among subgroups. FHC-high patients had a significantly longer PFS (hazard ratio [HR] = 0.69 [95% CI: 0.48–0.97], p = .0379) and OS (HR = 0.61 [95% CI: 0.39–0.93], p = .0210), when compared to FHC-negative patients. FHC-high was confirmed as an independent predictor for PFS and OS at multivariate analysis. No significant differences were found according to MN categories. FHC-high patients had a significantly higher incidence of irAEs of any grade, compared to FHC-negative patients (p = .0012). Conclusions: FHC-high patients seem to benefit more than FHC-negative patients from anti-PD-1/PD-L1 checkpoint inhibitors.

Published
2020

13. Clinicopathologic correlates of first-line pembrolizumab effectiveness in patients with advanced NSCLC and a PD-L1 expression of ≥ 50%

Author

Giovanni Mansueto, Lorenza Landi, Francesco Grossi, Cinzia Baldessari, Michele De Tursi, Alessio Cortellini, Vincenzo Sforza, Alain Gelibter, Raffaele Giusti, Biagio Ricciuti, Giuseppe Luigi Banna, Daniele Santini, Giorgia Guaitoli, Joachim G.J.V. Aerts, Russano Marco, Rita Chiari, Ornella Cantale, Luca Sala, Mariangela Torniai, Stefania Gori, Claudia Proto, Luigi Della Gravara, Diego Signorelli, Lorenzo Antonuzzo, Emilio Bria, Francesco Passiglia, Serena Ricciardi, Luca Cantini, Corrado Ficorella, Simona Carnio, Annamaria Catino, Paola Bordi, Vincenzo Di Noia, Miriam Grazia Ferrara, Maria Giovanna Dal Bello, Domenico Galetta, Sebastiano Buti, Federica Zoratto, Giampiero Porzio, Marianna Tudini, Paolo Marchetti, Diego Cortinovis, Erika Rijavec, Matteo Santoni, Carlo Genova, Danilo Rocco, Alex Friedlaender, Robert A. Belderbos, Ettore D'Argento, Simona Scodes, Pamela Pizzutilo, Marcello Tiseo, Alfredo Addeo, Marianna Macerelli, Rossana Berardi, Giada Targato, Federico Cappuzzo, Francesca Mazzoni, Alessandro Morabito, Fabrizio Citarella, Maria Rita Migliorino, Alessandro De Toma, Olga Nigro, Paolo Bironzo, Fausto Barbieri, Marco Filetti, Alessandro Tuzi, Giulio Metro, Francesca Rastelli, Alessio Grieco, and Pulmonary Medicine

Subjects
Oncology, Cancer Research, medicine.medical_treatment, Bone metastases, Liver metastases, PD-L1, Performance status, Radiotherapy, Smoking status, Pembrolizumab, carcinoma, Metastasis, Antineoplastic Agents, Immunological, bone metastases, Carcinoma, Non-Small-Cell Lung, middle aged, antineoplastic agents, Immunology and Allergy, antibodies, humans, humanized, adult, liver metastases, pd-l1, performance status, radiotherapy, smoking status, aged, antibodies, monoclonal, immunological, b7-h1 antigen, non-small-cell lung, female, lung neoplasms, male, progression-free survival, retrospective studies, Adult, Aged, Antibodies, Monoclonal, Humanized, Antineoplastic Agents, Immunological, B7-H1 Antigen, Carcinoma, Non-Small-Cell Lung, Female, Humans, Lung Neoplasms, Male, Middle Aged, Progression-Free Survival, Retrospective Studies, medicine.medical_specialty, Immunology, monoclonal, Antibodies, Monoclonal, Humanized, Internal medicine, medicine, Progression-free survival, Lung cancer, business.industry, Retrospective cohort study, medicine.disease, Radiation therapy, business
Abstract

Single-agent pembrolizumab represents the standard first-line option for metastatic non-small-cell lung cancer (NSCLC) patients with a PD-L1 (programmed death-ligand 1) expression of ≥ 50%. We conducted a multicenter retrospective study aimed at evaluating the clinicopathologic correlates of pembrolizumab effectiveness in patients with treatment-naive NSCLC and a PD-L1 expression of ≥ 50%. One thousand and twenty-six consecutive patients were included. The objective response rate (ORR) was 44.5% (95% CI 40.2–49.1), while the median progression free survival (PFS) and overall survival (OS) were 7.9 months (95% CI 6.9–9.5; 599 events) and 17.2 months (95% CI 15.3–22.3; 598 censored patients), respectively. ECOG-PS ≥ 2 (p

Published
2020

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

Author

Rosa Rita Silva, Antonino Grassadonia, Marco Russano, Michele De Tursi, Biagio Ricciuti, Raffaele Giusti, Rita Chiari, Katia Cannita, Sebastiano Buti, Daniele Santini, Corrado Ficorella, Federica Zoratto, Paolo Marchetti, Melissa Bersanelli, Maria Rita Migliorino, Paola Bordi, Giampiero Porzio, N. Tinari, Fabiana Perrone, Francesco Atzori, Enzo Veltri, Pietro Di Marino, Cecilia Anesi, Marco Filetti, Tea Zeppola, Rossana Berardi, Alessio Cortellini, Giulio Metro, Marcello Tiseo, Silvia Rinaldi, Marianna Tudini, Francesco Malorgio, Daniela Iacono, Annagrazia Pireddu, and Carlo Garufi

Subjects
0301 basic medicine, Oncology, Cancer Research, Multivariate analysis, medicine.medical_treatment, Pembrolizumab, carcinoma, NSCLC, survival analysis, 0302 clinical medicine, Immune-related adverse events, Carcinoma, Non-Small-Cell Lung, italy, middle aged, 80 and over, antibodies, humans, Aged, 80 and over, humanized, adult, aged, retrospective studies, female, Nivolumab, 030220 oncology & carcinogenesis, young adult, Immunotherapy, Pulmonary and Respiratory Medicine, medicine.medical_specialty, immune system diseases, monoclonal, lung neoplasms, Antibodies, Monoclonal, Humanized, programmed cell death 1 receptor, 03 medical and health sciences, Immune system, male, Internal medicine, medicine, Adverse effect, Lung cancer, business.industry, Surrogate endpoint, medicine.disease, non-small-cell lung, 030104 developmental biology, drug-related side effects and adverse reactions, treatment outcome, immune-related adverse events, immunotherapy, nivolumab, nsclc, pembrolizumab, business
Abstract

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).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.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.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.

Published
2019

15. Clinical Outcomes of Patients with Advanced Cancer and Pre-Existing Autoimmune Diseases Treated with Anti-Programmed Death-1 Immunotherapy: A Real-World Transverse Study

Author

Carlo Garufi, Antonino Grassadonia, Maria Giuseppa Vitale, Sergio Bracarda, Roberto Sabbatini, Tea Zeppola, Paolo A. Ascierto, Riccardo Marconcini, Andrea Botticelli, Marcello Tiseo, Cecilia Anesi, Giampiero Porzio, Raffaele Giusti, Gian Carlo Antonini Cappellini, Fabiana Perrone, Valeria Ciciarelli, Maria Concetta Fargnoli, Francesco Atzori, Sebastiano Buti, Enzo Veltri, Marco Filetti, Alessio Cortellini, Paolo Marchetti, Daniela Iacono, Michele De Tursi, Federica De Galitiis, Rossana Berardi, Annagrazia Pireddu, Davide Brocco, Melissa Bersanelli, Marianna Tudini, Rosa Rita Silva, Silvia Rinaldi, Federica Zoratto, Maria Rita Migliorino, Marco Russano, Antonio Rossi, Biagio Ricciuti, Katia Cannita, Francesco Malorgio, Maria Michiara, Rita Chiari, Daniele Santini, Nicola Tinari, and Corrado Ficorella

Subjects
Adult, Male, 0301 basic medicine, Cancer Research, medicine.medical_specialty, Drug-Related Side Effects and Adverse Reactions, medicine.medical_treatment, Programmed Cell Death 1 Receptor, Severity of Illness Index, Autoimmune Diseases, Young Adult, 03 medical and health sciences, Immune checkpoint inhibitors, Antineoplastic Agents, Immunological, 0302 clinical medicine, Acquired immunodeficiency syndrome (AIDS), Neoplasms, Internal medicine, Autoimmune disease, medicine, Humans, Anti-programmed death-1, Immunotherapy, Performance status, Sex, Oncology, Adverse effect, Aged, Retrospective Studies, Aged, 80 and over, business.industry, Incidence, Incidence (epidemiology), Middle Aged, medicine.disease, Immuno‐Oncology, Progression-Free Survival, Clinical trial, 030104 developmental biology, 030220 oncology & carcinogenesis, Female, business, Kidney cancer
Abstract

BACKGROUND. Patients with a history of autoimmune diseases (AIDs) have not usually been included in clinical trials with immune checkpoint inhibitors. MATERIALS AND METHODS. Consecutive patients with advanced cancer, treated with anti‐programmed death‐1 (PD‐1) agents, were evaluated according to the presence of pre‐existing AIDs. The incidence of immune‐related adverse events (irAEs) and clinical outcomes were compared among subgroups. RESULTS. A total of 751 patients were enrolled; median age was 69 years. Primary tumors were as follows: non‐small cell lung cancer, 492 (65.5%); melanoma, 159 (21.2%); kidney cancer, 94 (12.5%); and others, 6 (0.8%). Male/female ratio was 499/252. Eighty‐five patients (11.3%) had pre‐existing AIDs, further differentiated in clinically active (17.6%) and inactive (82.4%). Among patients with pre‐existing AIDs, incidence of irAEs of any grade was significantly higher when compared with patients without AIDs (65.9% vs. 39.9%). At multivariate analysis, both inactive (p = .0005) and active pre‐existing AIDs (p = .0162), female sex (p = .0004), and Eastern Cooperative Oncology Group Performance Status

Published
2019

16. A multicenter study of body mass index in cancer patients treated with anti-PD-1/PD-L1 immune checkpoint inhibitors: When overweight becomes favorable

Author

Mario Occhipinti, Gian Carlo Antonini Cappellini, Marco Filetti, Giampiero Porzio, Clara Natoli, Andrea De Giglio, Francesca Rastelli, Federica Zoratto, Silvia Rinaldi, Cecilia Anesi, Sebastiano Buti, Rita Chiari, Fabiana Perrone, Francesco Atzori, Pietro Di Marino, Andrea Botticelli, Enzo Veltri, Melissa Bersanelli, Federica Pergolesi, Nicola Tinari, Alessio Cortellini, Paolo A. Ascierto, Corrado Ficorella, Daniele Santini, Alain Gelibter, Marianna Tudini, Rossana Berardi, Maria Concetta Fargnoli, Tea Zeppola, Rosa Rita Silva, Marcello Tiseo, Riccardo Marconcini, Daniela Iacono, Raffaele Giusti, Federica De Galitiis, Annagrazia Pireddu, Paolo Marchetti, Alessandro Parisi, Francesco Malorgio, Maria Giuseppa Vitale, Michele De Tursi, Maria Michiara, Marco Russano, Biagio Ricciuti, Katia Cannita, Cortellini A., Bersanelli M., Buti S., Cannita K., Santini D., Perrone F., Giusti R., Tiseo M., Michiara M., Di Marino P., Tinari N., De Tursi M., Zoratto F., Veltri E., Marconcini R., Malorgio F., Russano M., Anesi C., Zeppola T., Filetti M., Marchetti P., Botticelli A., Antonini Cappellini G.C., De Galitiis F., Vitale M.G., Rastelli F., Pergolesi F., Berardi R., Rinaldi S., Tudini M., Silva R.R., Pireddu A., Atzori F., Chiari R., Ricciuti B., De Giglio A., Iacono D., Gelibter A., Occhipinti M.A., Parisi A., Porzio G., Fargnoli M.C., Ascierto P.A., Ficorella C., and Natoli C.

Subjects
Male, 0301 basic medicine, Cancer Research, Programmed Cell Death 1 Receptor, Kaplan-Meier Estimate, Anti-PD-1/PD-L1, Overweight, Gastroenterology, B7-H1 Antigen, Body Mass Index, Antineoplastic Agents, Immunological, 0302 clinical medicine, BMI, Cancer, Immunotherapy, Obesity, Immunology and Allergy, Immunology, Molecular Medicine, Oncology, Pharmacology, Renal cell carcinoma, Neoplasms, Molecular Targeted Therapy, Aged, 80 and over, Middle Aged, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, Treatment Outcome, 030220 oncology & carcinogenesis, Female, Underweight, medicine.symptom, Research Article, Adult, medicine.medical_specialty, lcsh:RC254-282, Young Adult, 03 medical and health sciences, Internal medicine, Biomarkers, Tumor, medicine, Humans, Aged, Neoplasm Staging, Proportional Hazards Models, business.industry, nutritional and metabolic diseases, Retrospective cohort study, medicine.disease, Clinical trial, 030104 developmental biology, business, Body mass index
Abstract

Background Recent evidence suggested a potential correlation between overweight and the efficacy of immune checkpoint inhibitors (ICIs) in cancer patients. Patients and methods We conducted a retrospective study of advanced cancer patients consecutively treated with anti-PD-1/PD-L1 inhibitors, in order to compare clinical outcomes according to baseline BMI levels as primary analysis. Based on their BMI, patients were categorized into overweight/obese (≥ 25) and non-overweight (

Published
2019

17. Adjuvant anastrozole versus exemestane versus letrozole, upfront or after 2 years of tamoxifen, in endocrine-sensitive breast cancer (FATA-GIM3): a randomised, phase 3 trial

Author

Sabino De Placido, Ciro Gallo, Michelino De Laurentiis, Giancarlo Bisagni, Grazia Arpino, Maria Giuseppa Sarobba, Ferdinando Riccardi, Antonio Russo, Lucia Del Mastro, Alessio Aligi Cogoni, Francesco Cognetti, Stefania Gori, Jennifer Foglietta, Antonio Frassoldati, Domenico Amoroso, Lucio Laudadio, Luca Moscetti, Filippo Montemurro, Claudio Verusio, Antonio Bernardo, Vito Lorusso, Adriano Gravina, Gabriella Moretti, Rossella Lauria, Antonella Lai, Carmela Mocerino, Sergio Rizzo, Francesco Nuzzo, Paolo Carlini, Francesco Perrone, Antonello Accurso, Biagio Agostara, Michele Aieta, Oscar Alabiso, Maria Grazia Alicicco, Dino Amadori, Laura Amaducci, Gianna Amiconi, Giustino Antuzzi, Mara Ardine, Antonio Ardizzoia, Caterina Aversa, Giuseppe Badalamenti, Sandro Barni, Carlo Basurto, Rossana Berardi, Cinzia Bergamasco, Paolo Bidoli, Claudia Bighin, Edoardo Biondi, Corrado Boni, Karen Borgonovo, Mario Botta, Stefano Bravi, Paolo Bruzzi, Giuseppe Buono, Alfredo Butera, Alessia Caldara, Giampiero Candeloro, Claudia Cappelletti, Cinzia Cardalesi, Elisabetta Carfora, Anna Cariello, Francesco Carrozza, Giacomo Cartenì, Michele Caruso, Virginia Casadei, Claudia Casanova, Luigi Castori, Luigi Cavanna, Giovanna Cavazzini, Marina Cazzaniga, Mario Chilelli, Paolo Chiodini, Silvia Chiorrini, Fortunato Ciardiello, Mariangela Ciccarese, Saverio Cinieri, Mario Clerico, Mariarosa Coccaro, Mario Comande, Claudia Corbo, Giuseppina Cortino, Stefania Cusenza, Gennaro Daniele, Alfonso Maria D'arco, Giuliana D'auria, Claudio Dazzi, Carmine De Angelis, Filippo de Braud, Gianfranco De Feo, Andrea De Matteis, Michele De Tursi, Anna Di Blasio, Giuseppe di Lucca, Liberato Di Lullo, Francesca Di Rella, Gianfranco Di Renzo, Pia Di Stefano, Aida Di Stefano, Anna Diana, Sara Donati, Agnese Fabbri, Alessandra Fabi, Marina Faedi, Gabriella Farina, Antonio Farris, Antonio Febbraro, Palma Fedele, Piera Federico, Francesco Ferraù, Gianluigi Ferretti, Antonella Ferro, Irene Floriani, Rosachiara Forcignanò, Samantha Forciniti, Valeria Forestieri, Gianni Fornari, Michela Frisinghelli, Vittorio Fusco, Giulia Gallizzi, Antonio Galvano, Antonio Gambardella, Angelo Gambi, Vittorio Gebbia, Erika Gervasi, Mara Ghilardi, Alice Giacobino, Giovanni Giardina, Francesco Giotta, Sara Giraudi, Mario Giuliano, Antonino Grassadonia, Donatella Grasso, Federica Grosso, Lorenzo Guizzaro, Pasquale Incoronato, Lorena Incorvaia, Giovanni Iodice, Nicla La Verde, Vincenzo Labonia, Gabriella Landi, Agnese Latorre, Vita Leonardi, Alessia Levaggi, Gennaro Limite, Linda Lina Bascialla, Lorenzo Livi, Evaristo Maiello, Daniela Mandelli, Ilaria Marcon, Daniela Menon, Michele Montedoro, Lucia Moraca, Anna Moretti, Maria Grazia Morritti, Patrizia Morselli, Antonella Mura, Silvia Mura, Michela Musacchio, Alberto Muzio, Donato Natale, Clara Natoli, Cinzia Nigro, Cecilia Nisticò, Antonio Nuzzo, Michele Orditura, Laura Orlando, Carmen Pacilio, Giuliano Palumbo, Raffaella Palumbo, Felice Pasini, Emanuela Paterno, Antonio Pazzola, Silvia Pelliccioni, Matilde Pensabene, Davide Perroni, Angela Pesenti Gritti, Fausto Petrelli, Maria Carmela Piccirillo, Graziella Pinotti, Claudia Pogliani, Davide Poli, Sonia Prader, Francesco Recchia, Daniele Rizzi, Carmen Romano, Rosalba Rossello, Chiara Rossini, Giuseppina Salvucci, Valeria Sanna, Alessandra Santini, Silvana Saracchini, Clementina Savastano, Giovanni Scambia, Francesco Schettini, Paola Schiavone, Alessio Schirone, Elena Seles, Simona Signoriello, Giuseppe Signoriello, Rosa Rita Silva, Antonia Silvestri, Vittorio Simeon, Ilaria Spagnoletti, Stefano Tamberi, Cristina Teragni, Verena Thalmann, Renato Thomas, Guglielmo Thomas, Amelia Tienghi, Nicola Tinari, Vincenza Tinessa, Federica Tomei, Giuseppe Tonini, Valter Torri, Divina Traficante, Marianna Tudini, Monica Turazza, Roberto Vignoli, Maria Giuseppa Vitale, Alessandra Zacchia, Pasquale Zagarese, Alda Zanni, Laura Zavallone, Maria Zavettieri, Alessandra Zoboli, De Placido, S., Gallo, C., De Laurentiis, M., Bisagni, G., Arpino, G., Sarobba, M. G., Riccardi, F., Russo, A., Del Mastro, L., Cogoni, A. A., Cognetti, F., Gori, S., Foglietta, J., Frassoldati, A., Amoroso, D., Laudadio, L., Moscetti, L., Montemurro, F., Verusio, C., Bernardo, A., Lorusso, V., Gravina, A., Moretti, G., Lauria, R., Lai, A., Mocerino, C., Rizzo, S., Nuzzo, F., Carlini, P., Perrone, F., Accurso, A., Agostara, B., Aieta, M., Alabiso, O., Alicicco, M. G., Amadori, D., Amaducci, L., Amiconi, G., Antuzzi, G., Ardine, M., Ardizzoia, A., Aversa, C., Badalamenti, G., Barni, S., Basurto, C., Berardi, R., Bergamasco, C., Bidoli, P., Bighin, C., Biondi, E., Boni, C., Borgonovo, K., Botta, M., Bravi, S., Bruzzi, P., Buono, G., Butera, A., Caldara, A., Candeloro, G., Cappelletti, C., Cardalesi, C., Carfora, E., Cariello, A., Carrozza, F., Carteni, G., Caruso, M., Casadei, V., Casanova, C., Castori, L., Cavanna, L., Cavazzini, G., Cazzaniga, M., Chilelli, M., Chiodini, P., Chiorrini, S., Ciardiello, F., Ciccarese, M., Cinieri, S., Clerico, M., Coccaro, M., Comande, M., Corbo, C., Cortino, G., Cusenza, S., Daniele, G., D'Arco, A. M., D'Auria, G., Dazzi, C., De Angelis, C., de Braud, F., De Feo, G., De Matteis, Ma., De Tursi, M., Di Blasio, A., di Lucca, G., Di Lullo, L., Di Rella, F., Di Renzo, G., Di Stefano, P., Di Stefano, A., Diana, A., Donati, S., Fabbri, A., Fabi, A., Faedi, M., Farina, G., Farris, A., Febbraro, A., Fedele, P., Federico, P., Ferrau, F., Ferretti, G., Ferro, A., Floriani, I., Forcignano, R., Forciniti, S., Forestieri, V., Fornari, G., Frisinghelli, M., Fusco, V., Gallizzi, G., Galvano, A., Gambardella, A., Gambi, A., Gebbia, V., Gervasi, E., Ghilardi, M., Giacobino, A., Giardina, G., Giotta, F., Giraudi, S., Giuliano, M., Grassadonia, A., Grasso, D., Grosso, F., Guizzaro, L., Incoronato, P., Incorvaia, L., Iodice, G., La Verde, N., Labonia, V., Landi, G., Latorre, A., Leonardi, V., Levaggi, A., Limite, G., Lina Bascialla, L., Livi, L., Maiello, E., Mandelli, D., Marcon, I., Menon, D., Montedoro, M., Moraca, L., Moretti, A., Morritti, M. G., Morselli, P., Mura, A., Mura, S., Musacchio, M., Muzio, A., Natale, D., Natoli, C., Nigro, C., Nistico, C., Nuzzo, A., Orditura, M., Orlando, L., Pacilio, C., Palumbo, G., Palumbo, R., Pasini, F., Paterno, E., Pazzola, A., Pelliccioni, S., Pensabene, M., Perroni, D., Pesenti Gritti, A., Petrelli, F., Piccirillo, M. C., Pinotti, G., Pogliani, C., Poli, D., Prader, S., Recchia, F., Rizzi, D., Romano, C., Rossello, R., Rossini, C., Salvucci, G., Sanna, V., Santini, A., Saracchini, S., Savastano, C., Scambia, G., Schettini, F., Schiavone, P., Schirone, A., Seles, E., Signoriello, S., Signoriello, G., Silva, R. R., Silvestri, A., Simeon, V., Spagnoletti, I., Tamberi, S., Teragni, C., Thalmann, V., Thomas, R., Thomas, G., Tienghi, A., Tinari, N., Tinessa, V., Tomei, F., Tonini, G., Torri, V., Traficante, D., Tudini, M., Turazza, M., Vignoli, R., Vitale, M. G., Zacchia, A., Zagarese, P., Zanni, A., Zavallone, L., Zavettieri, M., Zoboli, A., De Placido, Sabino, Gallo, Ciro, De Laurentiis, Michelino, Bisagni, Giancarlo, Arpino, Grazia, Sarobba, Maria Giuseppa, Riccardi, Ferdinando, Russo, Antonio, Del Mastro, Lucia, Cogoni, Alessio Aligi, Cognetti, Francesco, Gori, Stefania, Foglietta, Jennifer, Frassoldati, Antonio, Amoroso, Domenico, Laudadio, Lucio, Moscetti, Luca, Montemurro, Filippo, Verusio, Claudio, Bernardo, Antonio, Lorusso, Vito, Gravina, Adriano, Moretti, Gabriella, Lauria, Rossella, Lai, Antonella, Mocerino, Carmen, Rizzo, Sergio, Nuzzo, Francesco, Carlini, Paolo, Perrone, Francesco, Accurso, Antonello, Agostara, Biagio, Aieta, Michele, Alabiso, Oscar, Alicicco, Maria Grazia, Amadori, Dino, Amaducci, Laura, Amiconi, Gianna, Antuzzi, Giustino, Ardine, Mara, Ardizzoia, Antonio, Aversa, Caterina, Badalamenti, Giuseppe, Barni, Sandro, Basurto, Carlo, Berardi, Rossana, Bergamasco, Cinzia, Bidoli, Paolo, Bighin, Claudia, Biondi, Edoardo, Boni, Corrado, Borgonovo, Karen, Botta, Mario, Bravi, Stefano, Bruzzi, Paolo, Buono, Giuseppe, Butera, Alfredo, Caldara, Alessia, Candeloro, Giampiero, Cappelletti, Claudia, Cardalesi, Cinzia, Carfora, Elisabetta, Cariello, Anna, Carrozza, Francesco, Cartenì, Giacomo, Caruso, Michele, Casadei, Virginia, Casanova, Claudia, Castori, Luigi, Cavanna, Luigi, Cavazzini, Giovanna, Cazzaniga, Marina, Chilelli, Mario, Chiodini, Paolo, Chiorrini, Silvia, Ciardiello, Fortunato, Ciccarese, Mariangela, Cinieri, Saverio, Clerico, Mario, Coccaro, Mariarosa, Comande, Mario, Corbo, Claudia, Cortino, Giuseppina, Cusenza, Stefania, Daniele, Gennaro, D'arco, Alfonso Maria, D'auria, Giuliana, Dazzi, Claudio, De Angelis, Carmine, de Braud, Filippo, De Feo, Gianfranco, De Matteis, Andrea, De Tursi, Michele, Di Blasio, Anna, di Lucca, Giuseppe, Di Lullo, Liberato, Di Rella, Francesca, Di Renzo, Gianfranco, Di Stefano, Pia, Di Stefano, Aida, Diana, Anna, Donati, Sara, Fabbri, Agnese, Fabi, Alessandra, Faedi, Marina, Farina, Gabriella, Farris, Antonio, Febbraro, Antonio, Fedele, Palma, Federico, Piera, Ferraù, Francesco, Ferretti, Gianluigi, Ferro, Antonella, Floriani, Irene, Forcignanò, Rosachiara, Forciniti, Samantha, Forestieri, Valeria, Fornari, Gianni, Frisinghelli, Michela, Fusco, Vittorio, Gallizzi, Giulia, Galvano, Antonio, Gambardella, Antonio, Gambi, Angelo, Gebbia, Vittorio, Gervasi, Erika, Ghilardi, Mara, Giacobino, Alice, Giardina, Giovanni, Giotta, Francesco, Giraudi, Sara, Giuliano, Mario, Grassadonia, Antonino, Grasso, Donatella, Grosso, Federica, Guizzaro, Lorenzo, Incoronato, Pasquale, Incorvaia, Lorena, Iodice, Giovanni, La Verde, Nicla, Labonia, Vincenzo, Landi, Gabriella, Latorre, Agnese, Leonardi, Vita, Levaggi, Alessia, Limite, Gennaro, Lina Bascialla, Linda, Livi, Lorenzo, Maiello, Evaristo, Mandelli, Daniela, Marcon, Ilaria, Menon, Daniela, Montedoro, Michele, Moraca, Lucia, Moretti, Anna, Morritti, Maria Grazia, Morselli, Patrizia, Mura, Antonella, Mura, Silvia, Musacchio, Michela, Muzio, Alberto, Natale, Donato, Natoli, Clara, Nigro, Cinzia, Nisticò, Cecilia, Nuzzo, Antonio, Orditura, Michele, Orlando, Laura, Pacilio, Carmen, Palumbo, Giuliano, Palumbo, Raffaella, Pasini, Felice, Paterno, Emanuela, Pazzola, Antonio, Pelliccioni, Silvia, Pensabene, Matilde, Perroni, Davide, Pesenti Gritti, Angela, Petrelli, Fausto, Piccirillo, Maria Carmela, Pinotti, Graziella, Pogliani, Claudia, Poli, Davide, Prader, Sonia, Recchia, Francesco, Rizzi, Daniele, Romano, Carmen, Rossello, Rosalba, Rossini, Chiara, Salvucci, Giuseppina, Sanna, Valeria, Santini, Alessandra, Saracchini, Silvana, Savastano, Clementina, Scambia, Giovanni, Schettini, Francesco, Schiavone, Paola, Schirone, Alessio, Seles, Elena, Signoriello, Simona, Signoriello, Giuseppe, Silva, Rosa Rita, Silvestri, Antonia, Simeon, Vittorio, Spagnoletti, Ilaria, Tamberi, Stefano, Teragni, Cristina, Thalmann, Verena, Thomas, Renato, Thomas, Guglielmo, Tienghi, Amelia, Tinari, Nicola, Tinessa, Vincenza, Tomei, Federica, Tonini, Giuseppe, Torri, Valter, Traficante, Divina, Tudini, Marianna, Turazza, Monica, Vignoli, Roberto, Vitale, Maria Giuseppa, Zacchia, Alessandra, Zagarese, Pasquale, Zanni, Alda, Zavallone, Laura, Zavettieri, Maria, Zoboli, Alessandra, Mocerino, Carmela, D'Arco, Alfonso Maria, D'Auria, Giuliana, De Placido, S, Gallo, C, De Laurentiis, M, Bisagni, G, Arpino, G, Sarobba, M, Riccardi, F, Russo, A, Del Mastro, L, Cogoni, A, Cognetti, F, Gori, S, Foglietta, J, Frassoldati, A, Amoroso, D, Laudadio, L, Moscetti, L, Montemurro, F, Verusio, C, Bernardo, A, Lorusso, V, Gravina, A, Moretti, G, Lauria, R, Lai, A, Mocerino, C, Rizzo, S, Nuzzo, F, Carlini, P, Perrone, F, Accurso, A, Agostara, B, Aieta, M, Alabiso, O, Alicicco, M, Amadori, D, Amaducci, L, Amiconi, G, Antuzzi, G, Ardine, M, Ardizzoia, A, Aversa, C, Badalamenti, G, Barni, S, Basurto, C, Berardi, R, Bergamasco, C, Bidoli, P, Bighin, C, Biondi, E, Boni, C, Borgonovo, K, Botta, M, Bravi, S, Bruzzi, P, Buono, G, Butera, A, Caldara, A, Candeloro, G, Cappelletti, C, Cardalesi, C, Carfora, E, Cariello, A, Carrozza, F, Carteni, G, Caruso, M, Casadei, V, Casanova, C, Castori, L, Cavanna, L, Cavazzini, G, Cazzaniga, M, Chilelli, M, Chiodini, P, Chiorrini, S, Ciardiello, F, Ciccarese, M, Cinieri, S, Clerico, M, Coccaro, M, Comande, M, Corbo, C, Cortino, G, Cusenza, S, Daniele, G, D'Arco, A, D'Auria, G, Dazzi, C, De Angelis, C, de Braud, F, De Feo, G, De Matteis, A, De Tursi, M, Di Blasio, A, di Lucca, G, Di Lullo, L, Di Rella, F, Di Renzo, G, Di Stefano, P, Di Stefano, A, Diana, A, Donati, S, Fabbri, A, Fabi, A, Faedi, M, Farina, G, Farris, A, Febbraro, A, Fedele, P, Federico, P, Ferrau, F, Ferretti, G, Ferro, A, Floriani, I, Forcignano, R, Forciniti, S, Forestieri, V, Fornari, G, Frisinghelli, M, Fusco, V, Gallizzi, G, Galvano, A, Gambardella, A, Gambi, A, Gebbia, V, Gervasi, E, Ghilardi, M, Giacobino, A, Giardina, G, Giotta, F, Giraudi, S, Giuliano, M, Grassadonia, A, Grasso, D, Grosso, F, Guizzaro, L, Incoronato, P, Incorvaia, L, Iodice, G, La Verde, N, Labonia, V, Landi, G, Latorre, A, Leonardi, V, Levaggi, A, Limite, G, Lina Bascialla, L, Livi, L, Maiello, E, Mandelli, D, Marcon, I, Menon, D, Montedoro, M, Moraca, L, Moretti, A, Morritti, M, Morselli, P, Mura, A, Mura, S, Musacchio, M, Muzio, A, Natale, D, Natoli, C, Nigro, C, Nistico, C, Nuzzo, A, Orditura, M, Orlando, L, Pacilio, C, Palumbo, G, Palumbo, R, Pasini, F, Paterno, E, Pazzola, A, Pelliccioni, S, Pensabene, M, Perroni, D, Pesenti Gritti, A, Petrelli, F, Piccirillo, M, Pinotti, G, Pogliani, C, Poli, D, Prader, S, Recchia, F, Rizzi, D, Romano, C, Rossello, R, Rossini, C, Salvucci, G, Sanna, V, Santini, A, Saracchini, S, Savastano, C, Scambia, G, Schettini, F, Schiavone, P, Schirone, A, Seles, E, Signoriello, S, Signoriello, G, Silva, R, Silvestri, A, Simeon, V, Spagnoletti, I, Tamberi, S, Teragni, C, Thalmann, V, Thomas, R, Thomas, G, Tienghi, A, Tinari, N, Tinessa, V, Tomei, F, Tonini, G, Torri, V, Traficante, D, Tudini, M, Turazza, M, Vignoli, R, Vitale, M, Zacchia, A, Zagarese, P, Zanni, A, Zavallone, L, Zavettieri, M, and Zoboli, A

Subjects
Oncology, Receptor, ErbB-2, Settore MED/06 - Oncologia Medica, letrozole, law.invention, Adjuvant anastrozole, chemistry.chemical_compound, 0302 clinical medicine, Randomized controlled trial, Exemestane, law, exemestane, tamoxifen, breast cancer, Antineoplastic Combined Chemotherapy Protocols, 030212 general & internal medicine, Aromatase Inhibitors, Letrozole, Hazard ratio, Middle Aged, Receptors, Estrogen, Tolerability, Chemotherapy, Adjuvant, 030220 oncology & carcinogenesis, Female, Receptors, Progesterone, Breast Neoplasm, Human, medicine.drug, medicine.medical_specialty, Socio-culturale, Anastrozole, Breast Neoplasms, Disease-Free Survival, Drug Administration Schedule, 03 medical and health sciences, Breast cancer, Internal medicine, medicine, Aromatase Inhibitor, Humans, Aged, Antineoplastic Combined Chemotherapy Protocol, Androstadiene, business.industry, medicine.disease, Androstadienes, chemistry, business, Tamoxifen
Abstract

Background: Uncertainty exists about the optimal schedule of adjuvant treatment of breast cancer with aromatase inhibitors and, to our knowledge, no trial has directly compared the three aromatase inhibitors anastrozole, exemestane, and letrozole. We investigated the schedule and type of aromatase inhibitors to be used as adjuvant treatment for hormone receptor-positive early breast cancer. Methods: FATA-GIM3 is a multicentre, open-label, randomised, phase 3 trial of six different treatments in postmenopausal women with hormone receptor-positive early breast cancer. Eligible patients had histologically confirmed invasive hormone receptor-positive breast cancer that had been completely removed by surgery, any pathological tumour size, and axillary nodal status. Key exclusion criteria were hormone replacement therapy, recurrent or metastatic disease, previous treatment with tamoxifen, and another malignancy in the previous 10 years. Patients were randomly assigned in an equal ratio to one of six treatment groups: oral anastrozole (1 mg per day), exemestane (25 mg per day), or letrozole (2·5 mg per day) tablets upfront for 5 years (upfront strategy) or oral tamoxifen (20 mg per day) for 2 years followed by oral administration of one of the three aromatase inhibitors for 3 years (switch strategy). Randomisation was done by a computerised minimisation procedure stratified for oestrogen receptor, progesterone receptor, and HER2 status; previous chemotherapy; and pathological nodal status. Neither the patients nor the physicians were masked to treatment allocation. The primary endpoint was disease-free survival. The minimum cutoff to declare superiority of the upfront strategy over the switch strategy was assumed to be a 2% difference in disease-free survival at 5 years. Primary efficacy analyses were done by intention to treat; safety analyses included all patients for whom at least one safety case report form had been completed. Follow-up is ongoing. This trial is registered with the European Clinical Trials Database, number 2006-004018-42, and ClinicalTrials.gov, number NCT00541086. Findings: Between March 9, 2007, and July 31, 2012, 3697 patients were enrolled into the study. After a median follow-up of 60 months (IQR 46–72), 401 disease-free survival events were reported, including 211 (11%) of 1850 patients allocated to the switch strategy and 190 (10%) of 1847 patients allocated to upfront treatment. 5-year disease-free survival was 88·5% (95% CI 86·7–90·0) with the switch strategy and 89·8% (88·2–91·2) with upfront treatment (hazard ratio 0·89, 95% CI 0·73–1·08; p=0·23). 5-year disease-free survival was 90·0% (95% CI 87·9–91·7) with anastrozole (124 events), 88·0% (85·8–89·9) with exemestane (148 events), and 89·4% (87·3 to 91·1) with letrozole (129 events; p=0·24). No unexpected serious adverse reactions or treatment-related deaths occurred. Musculoskeletal side-effects were the most frequent grade 3–4 events, reported in 130 (7%) of 1761 patients who received the switch strategy and 128 (7%) of 1766 patients who received upfront treatment. Grade 1 musculoskeletal events were more frequent with the upfront schedule than with the switch schedule (924 [52%] of 1766 patients vs 745 [42%] of 1761 patients). All other grade 3–4 adverse events occurred in less than 2% of patients in either group. Interpretation: 5 years of treatment with aromatase inhibitors was not superior to 2 years of tamoxifen followed by 3 years of aromatase inhibitors. None of the three aromatase inhibitors was superior to the others in terms of efficacy. Therefore, patient preference, tolerability, and financial constraints should be considered when deciding the optimal treatment approach in this setting. Funding: Italian Drug Agency.

Published
2018

18. Family history of cancer as surrogate predictor for immunotherapy with anti-PD-1/PD-L1 immune checkpoint inhibitors: The FAMI-L1 study

Author

Raffaele Giusti, Francesca Rastelli, Marcello Tiseo, Paolo Marchetti, Daniele Santini, Alessandro Inno, Federica De Galitiis, Sebastiano Buti, Melissa Bersanelli, Federica Zoratto, Francesco Atzori, Clara Natoli, Sergio Bracarda, Corrado Ficorella, Alessio Cortellini, Maria Giuseppa Vitale, Rossana Berardi, Marianna Tudini, Paolo A. Ascierto, and Daniela Iacono

Subjects
Oncology, Cancer Research, medicine.medical_specialty, biology, business.industry, medicine.medical_treatment, Immune checkpoint inhibitors, Anti pd 1, Cancer, Immunotherapy, medicine.disease, Preliminary analysis, Internal medicine, PD-L1, medicine, biology.protein, cardiovascular diseases, Family history, business
Abstract

2559 Background: In the preliminary analysis of the FAMI-L1 study, we found a significant association between family history of cancer (FHC) and better clinical outcomes with anti-PD1/PD-L1 inhibitors. Methods: We retrospectively evaluated advanced cancer patients treated with single agents PD1/PD-L1 inhibitors. Patients were categorized as follow: FHC-high (in case of at least one cancer diagnoses in both straight and collateral family line), FHC-low (in case of a cancer diagnoses in only one family line) and FHC-negative. FHC was collected till the second degree of relatedness. Results: Between September 2013 and May 2018, 772 consecutive patients were evaluated. Median age was 68 years; male/female ratio was 521/251. Primary tumors were: NSCLC (58.3%), melanoma (22.1%), renal cell carcinoma (16.6%) and others (3%). 114 patients (14.9%) had ECOG-PS ≥ 2. 341 patients (44.3) were FHC-positive: 268 of them (34.75) were FHC-low while 74 (9.6%) were FHC-high. FHC-high patients had a significantly higher incidence of irAEs compared to FHC-negative (55.4% vs 35.6%; p = 0.0012) and to FHC-low (41.4%; p = 0.0323). No significant differences were found in terms of ORR among subgroups (data not shown). At median follow-up of 15.8 months, median PFS was 9.1 months (95%CI: 8.1-10.4; 452 events) and median OS was 19.7 months (95%CI: 15.7-24.4; 436 censored). No significant differences were found regarding PFS (data not shown). Median OS of FHC-high patients was 31.6 months (95%CI: 26.2-31.6; 50 censored patients), which was significantly longer than 18.2 months (95%CI: 14.7-21.3; 229 censored patients) of FHC-negative patients (HR = 0.60 [95%CI: 0.39–0.92), p = 0.0213). No significant differences in terms of OS were found between FHC-high/low patients (data not shown). After adjusting for primary tumor, sex, treatment-line, number of metastatic sites and ECOG-PS, FHC-high was confirmed an independent predictor of longer OS compared to FHC-negative (HR: 0.57 [95%CI: 0.37-0.88], p = 0.0098). Conclusions: FHC-high seems to be an independent predictor for longer OS in cancer patients treated with anti-PD-1/PD-L1. DNA damage and response (DDR) genes alterations may underlie that results.

Published
2019

19. Retinal metastasis regression with eribulin in a heavily pretreated breast cancer patient

Author

Eva Galizia, Giovanni Benedetti, Marta Gubbiotti, Luciano Latini, Barbara Pistilli, Marianna Tudini, and Marco Rusiello

Subjects
Oncology, Adult, Cancer Research, medicine.medical_specialty, Retinal Neoplasms, Antineoplastic Agents, Breast Neoplasms, Metastasis, chemistry.chemical_compound, Breast cancer, Internal medicine, medicine, Humans, Furans, business.industry, Brain Neoplasms, Retinal, General Medicine, Ketones, medicine.disease, Preclinical data, Combined Modality Therapy, Magnetic Resonance Imaging, Treatment Outcome, chemistry, Tolerability, Retreatment, Female, Clinical case, business, Eribulin
Abstract

The authors present the case of a heavily pretreated young woman with retinal and brain metastases from breast cancer who was successfully treated with eribulin. Eribulin was given at 1.1 mg/m2 on day 1 and 8, every 3 weeks for a total of 12 courses. A significant reduction in the size of brain and retinal lesions was achieved after three cycles. The treatment was continued for 12 cycles, with a good profile of tolerability. In this clinical case, eribulin demonstrated to be active on brain and retinal metastases from breast cancer, although preclinical data showed limited ability to cross the blood–brain barrier.

Published
2015

20. Modulation of GemOx chemotherapy according to CIRS in elderly patients with advanced pancreatic cancer

Author

Gemma Bruera, Eleonora Palluzzi, Enrico Ricevuto, Michela Pelliccione, Maria Vincenza Mancini, A. Santomaggio, Marianna Tudini, Corrado Ficorella, Paola Lanfiuti Baldi, and Katia Cannita

Subjects
Oncology, Male, Cancer Research, medicine.medical_specialty, Organoplatinum Compounds, medicine.medical_treatment, GemOx, Neutropenia, Gastroenterology, Deoxycytidine, Pancreatic cancer, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, Medicine, Humans, Aged, Neoplasm Staging, Aged, 80 and over, Chemotherapy, Leukopenia, business.industry, General Medicine, Middle Aged, medicine.disease, Survival Analysis, Gemcitabine, Oxaliplatin, Pancreatic Neoplasms, Treatment Outcome, Tolerability, Female, medicine.symptom, business, medicine.drug
Abstract

The present study evaluated activity and toxicity of modulated doses of gemcitabine associated to oxaliplatin in patients with secondary CIRS and with locally advanced pancreatic adenocarcinoma (LAPC) and metastatic pancreatic adenocarcinoma (MPC). Since January 2006, untreated LAPC and MPC patients have been assessed with ADL, IADL, CIRS to modulate chemotherapy dosages according to co-morbidity stage. Patiens aged

Published
2011

21. 'Poker' association of weekly alternating 5-fluorouracil, irinotecan, bevacizumab and oxaliplatin (FIr-B/FOx) in first line treatment of metastatic colorectal cancer: a phase II study

Author

Marianna Tudini, Corrado Ficorella, Paola Lanfiuti Baldi, Adelmo Antonucci, Federica De Galitiis, Katia Cannita, A. Santomaggio, Maria Vincenza Mancini, Paolo Marchetti, Enrico Ricevuto, and Gemma Bruera

Subjects
Adult, Oncology, Cancer Research, medicine.medical_specialty, Time Factors, Organoplatinum Compounds, Bevacizumab, Colorectal cancer, Phases of clinical research, Antibodies, Monoclonal, Humanized, Irinotecan, lcsh:RC254-282, Disease-Free Survival, Drug Administration Schedule, Surgical oncology, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, Genetics, medicine, Humans, Neoplasm Metastasis, Aged, business.industry, Antibodies, Monoclonal, Middle Aged, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, medicine.disease, Oxaliplatin, Treatment Outcome, Research Design, Fluorouracil, Camptothecin, Colorectal Neoplasms, business, Research Article, medicine.drug
Abstract

Background This phase II study investigated efficacy and safety of weekly alternating Bevacizumab (BEV)/Irinotecan (CPT-11) or Oxaliplatin (OHP) associated to weekly 5-Fluorouracil (5-FU) in first line treatment of metastatic colorectal carcinoma (MCRC). Methods Simon two-step design: delta 20% (p0 50%, p1 70%), power 80%, α 5%, β 20%. Projected objective responses (ORR): I step, 8/15 patients (pts); II step 26/43 pts. Schedule: weekly 12 h-timed-flat-infusion/5-FU 900 mg/m2, days 1-2, 8-9, 15-16, 22-23; CPT-11 160 mg/m2 plus BEV 5 mg/kg, days 1,15; OHP at three dose-levels, 60-70-80 mg/m2, days 8, 22; every 4 weeks. Results Fifty consecutive, unselected pts < 75 years were enrolled: median age 63; young-elderly (yE) 24 (48%); liver metastases (LM) 33 pts, 66% Achieved OHP recommended dose, 80 mg/m2. ORR 82% intent-to-treat and 84% as-treated analysis. Median progression-free survival 12 months. Equivalent efficacy was obtained in yE pts. Liver metastasectomies were performed in 26% of all pts and in 39% of pts with LM. After a median follow-up of 21 months, median overall survival was 28 months. Cumulative G3-4 toxicities per patient: diarrhea 28%, mucositis 6%, neutropenia 10%, hypertension 2%. They were equivalent in yE pts. Limiting toxicity syndromes (LTS), consisting of the dose-limiting toxicity, associated or not to G2 or limiting toxicities: 44% overall, 46% in yE. Multiple versus single site LTS, respectively: overall, 24% versus 20%; yE pts, 37.5% versus 8%. Conclusion Poker combination shows high activity and efficacy in first line treatment of MCRC. It increases liver metastasectomies rate and can be safely administered. Trial registration Osservatorio Nazionale sulla Sperimentazione Clinica dei Medicinali (OsSC) Agenzia Italiana del Farmaco (AIFA) Numero EudraCT 2007-004946-34

Published
2010

22. Phase II study of sorafenib in patients with sunitinib-refractory metastatic renal cell cancer

Author

Gianluca Giannarini, Giovannella Palmieri, Pasquale Rescigno, Sisto Perdonà, Nicola Longo, Gianni Bruni, Sandro Pignata, Giuseppe Di Lorenzo, Vincenzo Mirone, Riccardo Autorino, Michele De Laurentiis, Corrado Ficorella, Giacomo Cartenì, Sabino De Placido, Michele Aieta, Mimma Rizzo, Antonio Gonnella, Ciro Imbimbo, Marianna Tudini, Di Lorenzo, G, Cartenì, G, Autorino, R, Bruni, G, Tudini, M, Rizzo, M, Aieta, M, Gonnella, A, Rescigno, P, Perdonà, S, Giannarini, G, Pignata, S, Longo, N, Palmieri, G, Imbimbo, Ciro, DE LAURENTIIS, Michelino, Mirone, Vincenzo, Ficorella, C, DE PLACIDO, Sabino, DI LORENZO, G, Autorino, Riccardo, Imbimbo, C, DE LAURENTIIS, M, Mirone, V, DE PLACIDO, S., Di Lorenzo, G., Carteni, G., Autorino, R., Bruni, G., Tudini, M., Rizzo, M., Aieta, M., Gonnella, A., Rescigno, P., Perdona, S., Giannarini, G., Pignata, S., Longo, N., Palmieri, G., Imbimbo, C., De Laurentiis, M., Mirone, V., Ficorella, C., and De Placido, S.

Subjects
Phenylurea Compound, Adult, Male, Niacinamide, Sorafenib, Oncology, Cancer Research, medicine.medical_specialty, Indoles, Pyridines, Pyridine, Phases of clinical research, Antineoplastic Agents, Pyrrole, Metastasis, Antineoplastic Agent, Sorafenib, Sunitinib refractory, Internal medicine, Sunitinib, medicine, Humans, Pyrroles, Carcinoma, Renal Cell, Aged, business.industry, Phenylurea Compounds, Target Therapy, Benzenesulfonates, Benzenesulfonate, Kidney Neoplasm, Cancer, Metastatic Renal Cancer, Middle Aged, medicine.disease, Kidney Neoplasms, Surgery, Clinical trial, Tolerability, Indole, Female, business, Kidney cancer, Human, medicine.drug
Abstract

Purpose No previous prospective trials have been reported with sorafenib in patients with sunitinib-refractory metastatic renal cell cancer (MRCC). We conducted a multicenter study to determine the activity and tolerability of sorafenib as second-line therapy after sunitinib progression in MRCC. Patients and Methods Between January 2006 and September 2008, 52 patients were enrolled onto this single-arm phase II study. All patients received sorafenib 400 mg orally twice a day until disease progression or intolerable toxicity. The primary end point was objective response rate (complete or partial response) evaluated every 8 weeks by use of the Response Evaluation Criteria in Solid Tumors; secondary end points were toxicity, time to progression (TTP), and overall survival (OS). Results All patients were included in response and safety analyses. Partial responses were observed in 9.6% of patients (five of 52 patients; 95% CI, 5% to 17%) after two cycles. Grade 1 to 2 fatigue, diarrhea, nausea/vomiting, rash, and neutropenia were the most common side effects, noted in 16 (30.8%), 19 (36.5%), 20 (38.5%), 19 (36.5%), and 20 patients (38.5%), respectively. The most common grade 3 toxicity was diarrhea, noted in six patients (11.5%). Median TTP was 16 weeks (range, 8 to 40 weeks), and median OS was 32 weeks (range, 16 to 64 weeks). Conclusion Although well tolerated, sorafenib shows limited efficacy in sunitinib-refractory MRCC. Further randomized trials comparing sorafenib with other drugs that target different biologic pathways are needed to define the best second-line treatment option in these patients.

Published
2009

23. TIMED-FLAT INFUSION OF 5-FLUOROURACIL ASSOCIATED WITH DOCETAXEL AS FIRST-LINE TREATMENT OF PATIENTS WITH METASTATIC BREAST CANCER

Author

Giampiero Porzio, Enrico Ricevuto, Stefano Iacobelli, Christiana Zorica Di Rocco, Anna Iolanda Rispoli, Marianna Tudini, Paola Lanfiuti Baldi, M. F. Morelli, Katia Cannita, Paolo Marchetti, Nicola Tinari, Corrado Ficorella, Maria Vincenza Mancini, Giovanni Cianci, and A. Santomaggio

Subjects
Oncology, medicine.medical_specialty, business.industry, Treatment outcome, medicine.disease, Metastatic breast cancer, First line treatment, Breast cancer, Docetaxel, Fluorouracil, Internal medicine, Internal Medicine, medicine, Surgery, business, medicine.drug
Published
2008

24. Effective analgesic score: a 'marker' of the effects of chemotherapy on pain in advanced cancer patients?

Author

Giampiero Porzio, Marianna Tudini, Katia Cannita, Federica Aielli, Lucilla Verna, Ghazaleh Shodia-E-Razavi, and Corrado Ficorella

Subjects
Adult, Male, medicine.medical_specialty, medicine.medical_treatment, Treatment outcome, Analgesic, Pain, Antineoplastic Agents, Sensitivity and Specificity, Neoplasms, medicine, Terminal care, Humans, General Nursing, Nursing (all)2901 Nursing (miscellaneous), Aged, Pain Measurement, Retrospective Studies, Chemotherapy, Terminal Care, Middle Aged, Reproducibility of Results, Treatment Outcome, Anesthesiology and Pain Medicine, Neurology (clinical), Neurology, business.industry, Retrospective cohort study, Advanced cancer, Surgery, business
Published
2007

25. Efficacy of pregabalin in the management of cetuximab-related itch

Author

Corrado Ficorella, Claudio Porto, Federica Aielli, Katia Cannita, Marianna Tudini, Giampiero Porzio, and Lucilla Verna

Subjects
Oncology, Male, medicine.medical_specialty, Pregabalin, Cetuximab, Antineoplastic Agents, Antibodies, Internal medicine, Analgesics, Antibodies, Monoclonal, Antibodies, Monoclonal, Humanized, Humans, Middle Aged, Pruritus, Treatment Outcome, gamma-Aminobutyric Acid, Anesthesiology and Pain Medicine, Neurology (clinical), Neurology, Nursing (all)2901 Nursing (miscellaneous), Monoclonal, medicine, Humanized, General Nursing, business.industry, business, medicine.drug
Published
2006

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