8 results on '"Ficorella, C."'
Search Results
2. Real world data of cemiplimab in locally advanced and metastatic cutaneous squamous cell carcinoma.
- Author
-
Baggi A, Quaglino P, Rubatto M, Depenni R, Guida M, Ascierto PA, Trojaniello C, Queirolo P, Saponara M, Peris K, Spagnolo F, Bianchi L, De Galitiis F, Potenza MC, Proietti I, Marconcini R, Botticelli A, Barbieri V, Licitra L, Alfieri S, Ficorella C, Cortellini A, Fargnoli MC, Troiani T, Tondulli L, and Bossi P
- Subjects
- Adult, Aged, Aged, 80 and over, Antibodies, Monoclonal, Humanized adverse effects, Carcinoma, Squamous Cell immunology, Drug-Related Side Effects and Adverse Reactions immunology, Female, Humans, Immune Checkpoint Inhibitors adverse effects, Italy, Male, Middle Aged, Programmed Cell Death 1 Receptor antagonists & inhibitors, Response Evaluation Criteria in Solid Tumors, Retrospective Studies, Skin Neoplasms immunology, Young Adult, Antibodies, Monoclonal, Humanized administration & dosage, Carcinoma, Squamous Cell drug therapy, Drug-Related Side Effects and Adverse Reactions epidemiology, Immune Checkpoint Inhibitors administration & dosage, Skin Neoplasms drug therapy
- Abstract
Background: Cutaneous squamous cell carcinoma (cSCC) has an overall favourable outcome, except for patients with an advanced stage disease. The programmed death protein-1 (PD-1) inhibitor cemiplimab has been approved for use in advanced cSCC. We report clinical outcomes from the named patient programme-compassionate use of cemiplimab for patients with advanced cSCC in Italy., Methods: This is a retrospective, observational, multicentre study. We analysed medical records of patients with advanced cSCC treated with cemiplimab between May 2019 and February 2020 in 17 referral Italian centres. We assessed the safety profile according to the Common Terminology Criteria for Adverse Events, version 5.0 (CTCAE v 5.0), the clinical activity in terms of response rate, clinical benefit and duration of response and baseline clinical-pathologic characteristics associated with response., Results: 131 patients were included, with a median age of 79 years. Of them, 9.2% had a concurrent chronic lymphoproliferative disease and 8.5% a concomitant autoimmune disease. Some 42.7% of the total patients had at least one treatment-related adverse events (AEs); out of above, 9.2% had grade 3-4 adverse events, and there were two fatal adverse events. The overall response rate (ORR) was 58%, and the disease control rate (DCR) was 71.7%. Cutaneous squamous cell carcinomas (cSCCs) arising on the head and neck area (p = 0.007) and haemoglobin values in normal range (p = 0.034) were significantly associated with a better response, while cSCCs on the genitalia (p = 0.041), treatment with any systemic antibiotic within 1 month of cemiplimab initiation (p = 0.012), performance status ≥1 (p = 0.012), chronic corticosteroids therapy (p = 0.038), previous radiation therapy to lymph nodes (p = 0.052) and previous chemotherapy (p = 0.0020) were significantly associated with a worse response., Conclusions: Our real-world study showed safety and effectiveness results comparable to those obtained in clinical trials. We identified some clinical and biochemical factors potentially associated with response to cemiplimab., (Copyright © 2021 Elsevier Ltd. All rights reserved.)
- Published
- 2021
- Full Text
- View/download PDF
3. Predictive ability of a drug-based score in patients with advanced non-small-cell lung cancer receiving first-line immunotherapy.
- Author
-
Buti S, Bersanelli M, Perrone F, Bracarda S, Di Maio M, Giusti R, Nigro O, Cortinovis DL, Aerts JGJV, Guaitoli G, Barbieri F, Ferrara MG, Bria E, Grossi F, Bareggi C, Berardi R, Torniai M, Cantini L, Sforza V, Genova C, Chiari R, Rocco D, Della Gravara L, Gori S, De Tursi M, Di Marino P, Mansueto G, Zoratto F, Filetti M, Citarella F, Russano M, Mazzoni F, Garassino MC, De Toma A, Signorelli D, Gelibter A, Siringo M, Follador A, Bisonni R, Tuzi A, Minuti G, Landi L, Ricciardi S, Migliorino MR, Tabbò F, Olmetto E, Metro G, Adamo V, Russo A, Spinelli GP, Banna GL, Addeo A, Friedlaender A, Cannita K, Porzio G, Ficorella C, Carmisciano L, Pinato DJ, Mazzaschi G, Tiseo M, and Cortellini A
- Subjects
- Adrenal Cortex Hormones adverse effects, Aged, Anti-Bacterial Agents adverse effects, Antibodies, Monoclonal, Humanized adverse effects, Carcinoma, Non-Small-Cell Lung immunology, Carcinoma, Non-Small-Cell Lung mortality, Carcinoma, Non-Small-Cell Lung pathology, Clinical Decision-Making, Drug Interactions, Female, Humans, Immune Checkpoint Inhibitors adverse effects, Italy, Lung Neoplasms immunology, Lung Neoplasms mortality, Lung Neoplasms pathology, Male, Patient Selection, Polypharmacy, Predictive Value of Tests, Progression-Free Survival, Proton Pump Inhibitors adverse effects, Proton Pump Inhibitors therapeutic use, Reproducibility of Results, Retrospective Studies, Risk Assessment, Risk Factors, Adrenal Cortex Hormones therapeutic use, Anti-Bacterial Agents therapeutic use, Antibodies, Monoclonal, Humanized therapeutic use, Carcinoma, Non-Small-Cell Lung drug therapy, Decision Support Techniques, Immune Checkpoint Inhibitors therapeutic use, Immunotherapy adverse effects, Lung Neoplasms drug therapy
- Abstract
Background: We previously demonstrated the cumulative poor prognostic role of concomitant medications on the clinical outcome of patients with advanced cancer treated with immune checkpoint inhibitors, creating and validating a drug-based prognostic score to be calculated before immunotherapy initiation in patients with advanced solid tumours. This 'drug score' was calculated assigning score 1 for each between proton-pump inhibitor and antibiotic administration until a month before cancer therapy initiation and score 2 in case of corticosteroid intake. The good risk group included patients with score 0, intermediate risk with score 1-2 and poor risk with score 3-4., Methods: Aiming at validating the prognostic and putative predictive ability depending on the anticancer therapy, we performed the present comparative analysis in two cohorts of advanced non-small-cell lung cancer (NSCLC), respectively, receiving first-line pembrolizumab or chemotherapy through a random case-control matching and through a pooled multivariable analysis including the interaction between the computed score and the therapeutic modality (pembrolizumab vs chemotherapy)., Results: Nine hundred fifty and 595 patients were included in the pembrolizumab and chemotherapy cohorts, respectively. After the case-control random matching, 589 patients from the pembrolizumab cohort and 589 from the chemotherapy cohort were paired, with no statistically significant differences between the characteristics of the matched subjects. Among the pembrolizumab-treated group, good, intermediate and poor risk evaluable patients achieved an objective response rate (ORR) of 50.0%, 37.7% and 23.4%, respectively, (p < 0.0001), whereas among the chemotherapy-treated group, patients achieved an ORR of 37.0%, 40.0% and 32.4%, respectively (p = 0.4346). The median progression-free survival (PFS) of good, intermediate and poor risk groups was 13.9 months, 6.3 months and 2.8 months, respectively, within the pembrolizumab cohort (p < 0.0001), and 6.2 months, 6.2 months and 4.3 months, respectively, within the chemotherapy cohort (p = 0.0280). Among the pembrolizumab-treated patients, the median overall survival (OS) for good, intermediate and poor risk patients was 31.4 months, 14.5 months and 5.8 months, respectively, (p < 0.0001), whereas among the chemotherapy-treated patients, it was 18.3 months, 16.8 months and 10.6 months, respectively (p = 0.0003). A similar trend was reported considering the two entire populations. At the pooled analysis, the interaction term between the score and the therapeutic modality was statistically significant with respect to ORR (p = 0.0052), PFS (p = 0.0003) and OS (p < 0.0001), confirming the significantly different effect of the score within the two cohorts., Conclusion: Our 'drug score' showed a predictive ability with respect to ORR in the immunotherapy cohort only, suggesting it might be a useful tool for identifying patients unlikely to benefit from first-line single-agent pembrolizumab. In addition, the prognostic stratification in terms of PFS and OS was significantly more pronounced among the pembrolizumab-treated patients., Competing Interests: Conflict of interest statement S.B. received honoraria as a speaker at scientific events and for the advisory role from Bristol Myers Squibb (BMS), Pfizer, MSD, Ipsen, Roche, Eli Lilly, AstraZeneca and Novartis. M.B. received honoraria as a speaker at scientific events from Bristol Myers Squibb (BMS), Novartis, AstraZeneca and Pfizer and as a consultant for the advisory role from Novartis, BMS and Pfizer; she also received fees for copyright transfer from Sciclone Pharmaceuticals and research funding from Seqirus UK, Pfizer, Novartis, BMS, AstraZeneca, Roche S.p.A. and Sanofi Genzyme. R.G. received speaker fees and grant consultancies from AstraZeneca and Roche. J.G.J.V.A. reports receiving commercial research grants from Amphera and Roche, holds ownership interest (including patents) in Amphera BV and is a consultant/advisory board member for Amphera, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly, MSD and Roche. A.F. received grant consultancies from Roche, Pfizer, Astellas and BMS. F.M. received grant consultancies from MSD and Takeda. R.C. received speaker fees from BMS, MSD, Takeda, Pfizer, Roche and AstraZeneca. C.G. received speaker fees/grant consultancies from AstraZeneca, BMS, Boehringer Ingelheim, Roche and MSD. M.R. received honoraria for scientific events from Roche, AstraZeneca, BMS, MSD and Boehringer Ingelheim. E.B. received speaker and travel fees from MSD, AstraZeneca, Pfizer, Helsinn, Eli Lilly, BMS, Novartis and Roche and grant consultancies from Roche and Pfizer. M.C.G. received grants from MSD, AstraZeneca, Novartis, Roche, Pfizer, Celgene, Tiziana Sciences, Clovis, Merck, Bayer, GSK, Spectrum and Blueprint; personal fees from Eli Lilly, Boehringer Ingelheim, Otsuka Pharma, AstraZeneca, Novartis, BMS, Roche, Pfizer, Celgene, Incyte, Inivata, Takeda, Bayer, MSD, Sanofi, Seattle Genetics and Daiichi Sankyo and other financial supports from Eli Lilly, AstraZeneca, Novartis, BMS, Roche, Pfizer, Celgene, Tiziana Sciences, Clovis, Merck Serono, MSD, GSK, Spectrum and Blueprint. A.A. received grant consultancies from Takeda, MSD, BMJ, AstraZeneca, Roche and Pfizer. M.D.M. received research funding from Tesaro-GlaxoSmithKline and acted in a consulting/advisory role for Novartis, Pfizer, Eisai, Takeda, Janssen, Astellas, Roche and AstraZeneca. D.J.P. received lecture fees from ViiV Healthcare and Bayer Healthcare; travel expenses from BMS and Bayer Healthcare; consulting fees for Mina Therapeutics, EISAI, Roche and AstraZeneca and research funding (to the institution) from MSD and BMS. M.T. received honoraria from MSD, BMS, Boehringer (BI), Takeda and AstraZeneca and research funding from AstraZeneca. A.C. received speaker fees and grant consultancies from AstraZeneca, MSD, BMS, Roche, Novartis, Istituto Gentili and Astellas. All the other authors declare no competing interests., (Copyright © 2021 Elsevier Ltd. All rights reserved.)
- Published
- 2021
- Full Text
- View/download PDF
4. Post-progression outcomes of NSCLC patients with PD-L1 expression ≥ 50% receiving first-line single-agent pembrolizumab in a large multicentre real-world study.
- Author
-
Cortellini A, Cannita K, Tiseo M, Cortinovis DL, Aerts JGJV, Baldessari C, Giusti R, Ferrara MG, D'Argento E, Grossi F, Guida A, Berardi R, Morabito A, Genova C, Antonuzzo L, Mazzoni F, De Toma A, Signorelli D, Gelibter A, Targato G, Rastelli F, Chiari R, Rocco D, Gori S, De Tursi M, Mansueto G, Zoratto F, Filetti M, Bracarda S, Citarella F, Russano M, Cantini L, Nigro O, Buti S, Minuti G, Landi L, Ricciardi S, Migliorino MR, Natalizio S, Simona C, De Filippis M, Metro G, Adamo V, Russo A, Spinelli GP, Di Maio M, Banna GL, Friedlaender A, Addeo A, Pinato DJ, Ficorella C, and Porzio G
- Subjects
- Adult, Aged, Aged, 80 and over, Bone Neoplasms metabolism, Bone Neoplasms secondary, Carcinoma, Non-Small-Cell Lung metabolism, Carcinoma, Non-Small-Cell Lung pathology, Case-Control Studies, Female, Follow-Up Studies, Humans, Liver Neoplasms metabolism, Liver Neoplasms secondary, Lung Neoplasms metabolism, Lung Neoplasms pathology, Male, Middle Aged, Prognosis, Retrospective Studies, Survival Rate, Antibodies, Monoclonal, Humanized therapeutic use, Antineoplastic Agents, Immunological therapeutic use, B7-H1 Antigen metabolism, Bone Neoplasms drug therapy, Carcinoma, Non-Small-Cell Lung drug therapy, Liver Neoplasms drug therapy, Lung Neoplasms drug therapy
- Abstract
Background: Treatment sequencing with first-line immunotherapy, followed by second-line chemotherapy, is still a viable option for NSCLC patients with PD-L1 expression ≥50%., Methods: We evaluated post-progression treatment pathways in a large real-world cohort of metastatic NSCLC patients with PD-L1 expression ≥ 50% treated with first-line pembrolizumab monotherapy., Results: Overall, 974 patients were included. With a median follow-up of 22.7 months (95%CI: 21.6-38.2), the median overall survival (OS) of the entire population was 15.8 months (95%CI: 13.5-17.5; 548 events). At the data cutoff, among the 678 patients who experienced disease progression, 379 (55.9%) had not received any further treatment, and 359 patients (52.9%) had died. Patients who did not receive post-progression therapies were older (p = 0.0011), with a worse ECOG-PS (p < 0.0001) and were on corticosteroids prior to pembrolizumab (p = 0.0024). At disease progression, 198 patients (29.2%) received a switched approach and 101 (14.9%) received pembrolizumab ByPD either alone (64 [9.4%]) or in combination with local ablative treatments (37 [5.5%]) (LATs). After a random-case control matching according to ECOG-PS, CNS metastases, bone metastases, and (previous) best response to pembrolizumab, patients receiving pembrolizumab ByPD plus LATs were confirmed to have a significantly longer post-progression OS compared to patients receiving pembrolizumab ByPD alone 13.9 months versus 7.8 months (p = 0.0179) 241 patients (35.5%) among the 678 who had experienced PD, received a second-line systemic treatment (regardless of previous treatment beyond PD). As compared to first-line treatment commencement, patients' features at the moment of second-line initiation showed a significantly higher proportion of patients aged under 70 years (p = 0.0244), with a poorer ECOG-PS (p < 0.0001) and having CNS (p = 0.0001), bone (p = 0.0266) and liver metastases (p = 0.0148)., Conclusions: In the real-world scenario NSCLC patients with PD-L1 expression ≥50% treated with first-line single-agent pembrolizumab achieve worse outcomes as compared to the Keynote-024 trial. Poor post-progression outcomes are major determinants of the global results that should be considered when counselling patients for first-line treatment choices., Competing Interests: Conflict of interest statement Dr Alessio Cortellini received speaker fees and grant consultancies by Astrazeneca, MSD, BMS, Roche, Novartis, Istituto Gentili and Astellas. Dr Raffaele Giusti received speaker fees and grant consultancies by Astrazeneca and Roche. Dr Joachim GJV Aerts reports receiving commercial research grants from Amphera and Roche, holds ownership interest (including patents) in Amphera BV, and is a consultant/advisory board member for Amphera, Boehringer Ingelheim, Bristol-Myers Squibb, Eli-Lilly, MSD and Roche. Dr Alex Friedlaender received grant consultancies by Roche, Pfizer, Astellas and BMS. Dr Alessandro Morabito received speaker fees by Astra, Roche, BMS, MSD, Boehringer, Pfizer, Takeda. Dr Francesca Mazzoni received grant consultancies by MSD and Takeda. Dr Rita Chiari received speaker fees by BMS, MSD, Takeda, Pfizer, Roche and Astrazeneca. Dr Carlo Genova received speaker fees/grant consultancies by Astrazeneca, BMS, Boehringer-Ingelheim, Roche and MSD. Dr Marco Russano received honoraria for scientific events by Roche, Astrazeneca, BMS, MSD and Boehringer Ingelheim. Dr Marcello Tiseo received speakers’ and consultants’ fee from Astra-Zeneca, Pfizer, Eli-Lilly, BMS, Novartis, Roche, MSD, Boehringer Ingelheim, Otsuka, Takeda, Pierre Fabre. Dr Alfredo Addeo received grant consultancies by Takeda, MSD, BMJ, Astrazeneca, Roche and Pfizer. Dr Rita Chiari received speaker fees by BMS, MSD, Takeda, Pfizer, Roche and Astrazeneca. Dr Carlo Genova received speaker fees/grant consultancies by Astrazeneca, BMS, Boehringer-Ingelheim, Roche and MSD. Dr David J Pinato received lecture fees from ViiV Healthcare, Bayer Healthcare and travel expenses from BMS and Bayer Healthcare; consulting fees for Mina Therapeutics, EISAI, Roche, Astra Zeneca; received research funding (to institution) from MSD, BMS. All other authors declare no competing interests., (Copyright © 2021 Elsevier Ltd. All rights reserved.)
- Published
- 2021
- Full Text
- View/download PDF
5. Effect of concomitant medications with immune-modulatory properties on the outcomes of patients with advanced cancer treated with immune checkpoint inhibitors: development and validation of a novel prognostic index.
- Author
-
Buti S, Bersanelli M, Perrone F, Tiseo M, Tucci M, Adamo V, Stucci LS, Russo A, Tanda ET, Spagnolo F, Rastelli F, Pergolesi F, Santini D, Russano M, Anesi C, Giusti R, Filetti M, Marchetti P, Botticelli A, Gelibter A, Occhipinti MA, Ferrari M, Vitale MG, Nicolardi L, Chiari R, Rijavec E, Nigro O, Tuzi A, De Tursi M, Di Marino P, Conforti F, Queirolo P, Bracarda S, Macrini S, Gori S, Zoratto F, Veltri E, Di Cocco B, Mallardo D, Vitale MG, Santoni M, Patruno L, Porzio G, Ficorella C, Pinato DJ, Ascierto PA, and Cortellini A
- Subjects
- Adult, Aged, Aged, 80 and over, Female, Humans, Male, Middle Aged, Prognosis, Reproducibility of Results, Treatment Outcome, Carcinoma, Non-Small-Cell Lung drug therapy, Immune Checkpoint Inhibitors therapeutic use, Immunotherapy methods, Lung Neoplasms drug therapy
- Abstract
Background: Concomitant medications are known to impact on clinical outcomes of patients treated with immune checkpoint inhibitors (ICIs). We aimed weighing the role of different concomitant baseline medications to create a drug-based prognostic score., Methods: We evaluated concomitant baseline medications at immunotherapy initiation for their impact on objective response rate (ORR), progression-free survival (PFS) and overall survival (OS) in a single-institution cohort of patients with advanced cancer treated with ICIs (training cohort, N = 217), and a drug-based prognostic score with the drugs resulting significantly impacting the OS was computed. Secondly, we externally validated the score in a large multicenter external cohort (n = 1012)., Results: In the training cohort (n = 217), the median age was 69 years (range: 32-89), and the primary tumours were non-small-cell lung cancer (70%), melanoma (14.7%), renal cell carcinoma (9.2%) and others (6%). Among baseline medications, corticosteroids (hazard ratio [HR] = 2.3; 95% confidence interval [CI]: 1.60-3.30), systemic antibiotics (HR = 2.07; 95% CI: 1.31-3.25) and proton-pump inhibitors (PPIs) (HR = 1.57; 95% CI: 1.13-2.18) were significantly associated with OS. The prognostic score was calculated using these three drug classes, defining good, intermediate and poor prognosis patients. Within the training cohort, OS (p < 0.0001), PFS (p < 0.0001) and ORR (p = 0.0297) were significantly distinguished by the score stratification. The prognostic value of the score was also demonstrated in terms of OS (p < 0.0001), PFS (p < 0.0001) and ORR (p = 0.0006) within the external cohort., Conclusion: Cumulative exposure to corticosteroids, antibiotics and PPIs (three likely microbiota-modulating drugs) leads to progressively worse outcomes after ICI therapy. We propose a simple score that can help stratifying patients in routine practice and clinical trials of ICIs., Competing Interests: Conflict of interest statement M.B. reports receiving research funding by Roche, Seqirus, Pfizer and Novartis and personal fees as a speaker/consultant from AstraZeneca, Novartis, Pfizer and BMS. M.T. reports receiving speaker fees and grant consultancies from AstraZeneca, Pfizer, Eli-Lilly, BMS, Novartis, Roche, MSD, Boehringer Ingelheim, Otsuka, Takeda and Pierre Fabre. A.C. reports receiving speaker fees and grant consultancies from Roche, MSD, BMS, AstraZeneca, Novartis and Astellas. R.G. reports receiving speaker fees and grant consultancies from AstraZeneca and Roche. M.G.V. reports receiving speaker fees, grant consultancies and travel support from BMS, Ipsen, Novartis, Pfizer, Astellas, Jansen and Pierre-Fabre. A.R. reports receiving grant consultancies from AstraZeneca and MSD. F.S. reports receiving speaker fees and grant consultancies from Roche, Novartis, BMS, MSD, Pierre-Fabre, Sanofi, Merck and Sunpharma. D.J.P. reports receiving lecture fees from ViiV Healthcare and Bayer Healthcare; travel expenses from BMS and Bayer Healthcare; consulting fees for Mina Therapeutics, EISAI, Roche and AstraZeneca and research funding (to institution) from MSD and BMS. P.A.A. reports receiving speaker fees and grant consultancies from BMS, Roche-Genentech, MSD, Dohme, Array, Novartis, Merck-Serono, Pierre-Fabre, Incyte, New Link Genetics, Genmab, Medimmune, AstraZeneca, Syndax, SunPharma, Sanofi, Idera, Ultimovacs, Sandoz, Immunocore, 4SC, Alkermes, Italfarmaco, Nektar and Boehringer-Ingelheim and research funds from BMS, Roche-Genentech and Array. All other authors declared no competing interests., (Copyright © 2020 Elsevier Ltd. All rights reserved.)
- Published
- 2021
- Full Text
- View/download PDF
6. Late immune-related adverse events in long-term responders to PD-1/PD-L1 checkpoint inhibitors: A multicentre study.
- Author
-
Nigro O, Pinotti G, De Galitiis F, Di Pietro FR, Giusti R, Filetti M, Bersanelli M, Lazzarin A, Bordi P, Catino A, Pizzutilo P, Galetta D, Marchetti P, Botticelli A, Scagnoli S, Russano M, Santini D, Torniai M, Berardi R, Ricciuti B, De Giglio A, Chiari R, Russo A, Adamo V, Tudini M, Silva RR, Bolzacchini E, Giordano M, Di Marino P, De Tursi M, Rijavec E, Ghidini M, Vallini I, Stucci LS, Tucci M, Pala L, Conforti F, Queirolo P, Tanda E, Spagnolo F, Cecchi F, Bracarda S, Macrini S, Santoni M, Battelli N, Fargnoli MC, Porzio G, Tuzi A, Suter MB, Ficorella C, and Cortellini A
- Subjects
- Adult, Aged, Aged, 80 and over, Drug-Related Side Effects and Adverse Reactions pathology, Female, Follow-Up Studies, Humans, Male, Middle Aged, Neoplasms immunology, Neoplasms pathology, Prognosis, Retrospective Studies, Survival Rate, Antineoplastic Agents, Immunological adverse effects, Drug-Related Side Effects and Adverse Reactions etiology, Immunotherapy adverse effects, Neoplasms drug therapy
- Abstract
Background: Data on spectrum and grade of immune-related adverse events (irAEs) in long-term responders to immune checkpoint inhibitors (ICIs) are lacking., Methods: We performed a retrospective multicenter study to characterized irAEs occurring after a 12-months minimum treatment period with PD-(L)1 ICIs in patients with advanced cancer. IrAEs were categorized into 'early' (≤12 months) and 'late' (>12 months)., Results: From September 2013 to October 2019, 436 consecutive patients were evaluated. Two hundred twenty-three experienced any grade early-irAEs (51.1%), whereas 132 experienced any grade late-irAEs (30.3%) (p < 0.0001). Among the latter, 29 (22%) experienced a recurrence of an early-irAEs, whereas 103 (78%) experienced de novo late-irAEs involving different system/organ. Among patients with late-irAEs, 21 experienced GIII/GIV irAEs (4.8%). Median time to onset of early-irAEs was 3.4 months (95% confidence interval [CI]: 2.8-4.2), whereas 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 (hazard ratio [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). In addition, the time-adjusted cumulative risk of death in accordance with 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., Conclusion: 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., Competing Interests: Conflict of interest statement A.C. reports having received grants as speaker by MSD and Astra-Zeneca; grant consultancies by BMS, Roche, Novartis, Istituto Gentili and Ipsen. M.B. reports having received research funding by Roche, Pfizer, Seqirus, AstraZeneca, Bristol-Myers Squibb, Novartis and Sanofi; she also received honoraria for advisory role and as speaker at scientific events by Bristol-Myers Squibb, Novartis and Pfizer. M.R. reports having received honoraria for scientific events by Roche, Astrazeneca, Bristol-Myers Squibb, Merck Sharp & Dohme and Boehringer Ingelheim. R.G. reports to be a part of the advisory boards/Honoraria/Speakers’ fee/Consultant for: Astra Zeneca, Roche. All remaining authors declare no conflict of interest., (Copyright © 2020 Elsevier Ltd. All rights reserved.)
- Published
- 2020
- Full Text
- View/download PDF
7. 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
-
Cortellini A, Bersanelli M, Santini D, Buti S, Tiseo M, Cannita K, Perrone F, Giusti R, De Tursi M, Zoratto F, Marconcini R, Russano M, Zeppola T, Anesi C, Filetti M, Marchetti P, Botticelli A, Gelibter A, De Galitiis F, Vitale MG, Rastelli F, Tudini M, Silva RR, Atzori F, Chiari R, Ricciuti B, De Giglio A, Migliorino MR, Mallardo D, Vanella V, Mosillo C, Bracarda S, Rinaldi S, Berardi R, Natoli C, Ficorella C, Porzio G, and Ascierto PA
- Subjects
- Adult, Aged, Aged, 80 and over, Antineoplastic Agents, Immunological administration & dosage, B7-H1 Antigen antagonists & inhibitors, B7-H1 Antigen immunology, Drug-Related Side Effects and Adverse Reactions diagnosis, Drug-Related Side Effects and Adverse Reactions immunology, Female, Humans, Incidence, Male, Middle Aged, Neoplasms immunology, Obesity diagnosis, Obesity immunology, Programmed Cell Death 1 Receptor antagonists & inhibitors, Programmed Cell Death 1 Receptor immunology, Retrospective Studies, Risk Factors, Severity of Illness Index, Young Adult, Antineoplastic Agents, Immunological adverse effects, Body Mass Index, Drug-Related Side Effects and Adverse Reactions epidemiology, Neoplasms drug therapy, Obesity epidemiology
- Abstract
Background: 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., Patients and Methods: 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., Results: 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., Conclusions: 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'., Competing Interests: Declaration of competing interest Dr Alessio Cortellini received grants as speaker by MSD and Astra-Zeneca, grant consultancies by MSD, BMS, Roche, Novartis, Istituto Gentili, Astellas and Ipsen; Prof Clara Natoli received travel grants/personal fees from Pfizer, EISAI, Novartis, MSD, BMS and Astra-Zeneca; Dr Maria G Vitale received grant as consultant for advisory role, travel and speaker fees by BMS, Ipsen, Novartis and Pfizer, Jansen, Astellas and Pierre Fabre; Dr Raffaele Giusti received honoraria for lectures, consultation or advisory board participation from Kiowakirin, Angelini, Bristol-Myers Squibb, Boehringer-Ingelheim, MSD, Roche and Astra-Zeneca; Dr Melissa Bersanelli received research funding by Sanofi Genzyme, BMS, MSD, AstraZeneca, Seqirus, Roche, Novartis, Pfizer; honoraria as scientific speaker and advisory board consultant for BMS, Novartis, Pfizer. All other authors declared no competing interests., (Copyright © 2020 Elsevier Ltd. All rights reserved.)
- Published
- 2020
- Full Text
- View/download PDF
8. Does pain intensity predict a poor opioid response in cancer patients?
- Author
-
Mercadante S, Gebbia V, David F, Aielli F, Verna L, Porzio G, Ferrera P, Casuccio A, and Ficorella C
- Subjects
- Aged, Analysis of Variance, Female, Humans, Karnofsky Performance Status, Male, Middle Aged, Pain etiology, Pain Measurement, Prospective Studies, Treatment Outcome, Analgesics, Opioid therapeutic use, Neoplasms complications, Pain prevention & control
- Abstract
Aim: The aim of this study was to test the hypothesis that initial pain intensity is not a predictive factor of poor opioid response in advanced cancer patients, as suggested by a recent work., Methods: A secondary analysis of one-hundred-sixty-seven patients referred for treatment of cancer-related pain was conducted. Pain intensity at admission was recorded and patients were divided in three categories of pain intensity: mild, moderate and severe. Patients were offered a treatment with opioid dose titration, according to department policy. Data regarding opioid doses and pain intensity were collected after dose titration was completed. Four levels of opioid response were considered: (a) good pain control, with minimal opioid escalation and without relevant adverse effects; (b) good pain control requiring more aggressive opioid escalation, for example doubling the doses in four days; (c) adequate pain control associated with the occurrence of adverse effects; (d) poor pain control with adverse effects., Results: Seventy-six, forty-four, forty-one and six patients showed a response a, b, c, and d, respectively. No correlation between baseline pain intensity categories and opioid response was found. Patients with response 'b' and 'd' showed higher values of OEImg., Conclusion: Baseline pain intensity does not predict the outcome after an appropriate opioid titration. It is likely that non-homogeneous pain treatment would have biased the outcome of a previous work., (Copyright © 2011 Elsevier Ltd. All rights reserved.)
- Published
- 2011
- Full Text
- View/download PDF
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.