Alessio Cortellini1, Alex Friedlaender2, Giuseppe L Banna3, Giampiero Porzio4, Melissa Bersanelli5, Federico Cappuzzo6, Joachim G J V Aerts7, Raffaele Giusti8, Emilio Bria9, Diego Cortinovis10, Francesco Grossi11, Maria R Migliorino12, Domenico Galetta13, Francesco Passiglia14, Rossana Berardi15, Francesca Mazzoni16, Vincenzo Di Noia17, Diego Signorelli18, Alessandro Tuzi19, Alain Gelibter20, Paolo Marchetti21, Marianna Macerelli22, Francesca Rastelli23, Rita Chiari24, Danilo Rocco25, Alessandro Inno26, Pietro Di Marino27, Giovanni Mansueto28, Federica Zoratto29, Matteo Santoni30, Marianna Tudini31, Michele Ghidini11, Marco Filetti8, Annamaria Catino13, Pamela Pizzutilo13, Luca Sala10, Mario Alberto Occhipinti20, Fabrizio Citarella32, Russano Marco32, Mariangela Torniai15, Luca Cantini33, Alessandro Follador22, Vincenzo Sforza34, Olga Nigro19, Miriam G Ferrara9, Ettore D'Argento35, Alessandro Leonetti5, Linda Pettoruti5, Lorenzo Antonuzzo16, Simona Scodes6, Lorenza Landi6, Giorgia Guaitoli36, Cinzia Baldessari36, Federica Bertolini36, Luigi Della Gravara25, Maria Giovanna Dal Bello37, Robert A Belderbos7, Marco De Filippis14, Cristina Cecchi14, Serena Ricciardi12, Clelia Donisi38, Alessandro De Toma18, Claudia Proto18, Alfredo Addeo2, Ornella Cantale3, Biagio Ricciuti39, Carlo Genova37, Alessandro Morabito34, Daniele Santini32, Corrado Ficorella4, Katia Cannita40. 1. Medical Oncology, St Salvatore Hospital, L'Aquila, Italy; Department of Biotechnology and Applied Clinical Sciences, University of L'Aquila, L'Aquila, Italy. Electronic address: alessiocortellini@gmail.com. 2. Oncology Department, University Hospital of Geneva, Geneva, Switzerland. 3. Oncology Department, United Lincolnshire Hospital NHS Trust, Lincoln, UK. 4. Medical Oncology, St Salvatore Hospital, L'Aquila, Italy; Department of Biotechnology and Applied Clinical Sciences, University of L'Aquila, L'Aquila, Italy. 5. Medical Oncology Unit, University Hospital of Parma, Parma, Italy. 6. Department of Oncology and Hematology, AUSL Romagna, Ravenna, Italy. 7. Department of Pulmonary Diseases, Erasmus Medical Center, Rotterdam, the Netherlands. 8. Medical Oncology, St. Andrea Hospital, Rome, Italy. 9. Comprehensive Cancer Center, Fondazione Policlinico Universitario "A. Gemelli" IRCCS, Rome, Italy; Department of Translational Medicine and Surgery, Università Cattolica del Sacro Cuore, Rome, Italy. 10. Medical Oncology, Ospedale San Gerardo, Monza, Italy. 11. Medical Oncology Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy. 12. Pneumo-Oncology Unit, St. Camillo-Forlanini Hospital, Rome, Italy. 13. Thoracic Oncology Unit, Clinical Cancer Centre IRCCS Istituto Tumori "Giovanni Paolo II", Bari, Italy. 14. Department of Oncology, University of Turin, San Luigi Hospital, Orbassano (TO), Italy. 15. Oncology Clinic, Università Politecnica Delle Marche, Ospedali Riuniti Di Ancona, Ancona, Italy. 16. Department of Oncology, Careggi University Hospital, Florence, Italy. 17. Medical Oncology, University Hospital of Foggia, Foggia, Italy. 18. Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy. 19. Medical Oncology, ASST-Sette Laghi, Varese, Italy. 20. Medical Oncology (B), Policlinico Umberto I, "Sapienza" University of Rome, Rome, Italy. 21. Medical Oncology, St. Andrea Hospital, Rome, Italy; Medical Oncology (B), Policlinico Umberto I, "Sapienza" University of Rome, Rome, Italy; Department of Clinical and Molecular Medicine, "Sapienza" University of Rome, Rome, Italy. 22. Department of Oncology, University Hospital Santa Maria Della Misericordia, Udine, Italy. 23. Medical Oncology, Fermo Area Vasta 4, Fermo, Italy. 24. Medical Oncology, Ospedali Riuniti Padova Sud "Madre Teresa Di Calcutta", Monselice, Italy. 25. Pneumo-Oncology Unit, Monaldi Hospital, Naples, Italy. 26. Oncology Unit, Ospedale Sacro Cuore don Calabria Cancer Care Center, Negrar, VR, Italy. 27. Clinical Oncology Unit, S.S. Annunziata Hospital, Chieti, Italy. 28. Medical Oncology, F. Spaziani Hospital, Frosinone, Italy. 29. Medical Oncology, Santa Maria Goretti Hospital, Latina, Italy. 30. Department of Oncology, Macerata Hospital, Macerata, Italy. 31. Medical Oncology, AV2 Fabriano ASUR Marche, Fabriano, Italy. 32. Medical Oncology, Campus Bio-Medico University, Rome, Italy. 33. Department of Pulmonary Diseases, Erasmus Medical Center, Rotterdam, the Netherlands; Oncology Clinic, Università Politecnica Delle Marche, Ospedali Riuniti Di Ancona, Ancona, Italy. 34. Thoracic Medical Oncology, Istituto Nazionale Tumori 'Fondazione G Pascale', IRCCS, Napoli, Italy. 35. Comprehensive Cancer Center, Fondazione Policlinico Universitario "A. Gemelli" IRCCS, Rome, Italy. 36. Department of Oncology and Hematology, Modena University Hospital, Modena, Italy. 37. Lung Cancer Unit, IRCCS Ospedale Policlinico San Martino, Genova, Italy. 38. Medical Oncology Unit, University Hospital and University of Cagliari, Cagliari, Italy. 39. Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA; Division of Medical Oncology, S.Orsola-Malpighi Hospital, University of Bologna, Bologna, Italy. 40. Medical Oncology, St Salvatore Hospital, L'Aquila, Italy.
Abstract
BACKGROUND: The role of immune-related adverse events (irAEs), as a surrogate predictor of the efficacy of checkpoint inhibitors, has not yet been described in the setting of first-line, single-agent pembrolizumab for patients with metastatic non-small-cell lung-cancer (NSCLC) with a programmed death-ligand 1 (PD-L1) expression of ≥ 50%. PATIENTS AND METHODS: We previously conducted a multicenter retrospective analysis in patients with treatment-naive metastatic NSCLC and a PD-L1 expression of ≥ 50% receiving first-line pembrolizumab. Here, we report the results of the irAE analysis and the potential correlation between irAEs and clinical outcomes. RESULTS: A total of 1010 patients were included in this analysis; after a 6-week landmark selection, 877 (86.8%) patients were included in the efficacy analysis. Any grade irAEs (P < .0001), grade 3/4 irAEs (P = .0025), leading to discontinuation irAEs (P = .0144), multiple-site and single-site irAEs (P < .0001), cutaneous irAEs (P = .0001), endocrine irAEs (P = .0227), pulmonary irAEs (P = .0479), and rheumatologic irAEs (P = .0018) were significantly related to a higher objective response rate. Any grade irAEs (P < .0001), single-site irAEs (P < .0001), multiple-site irAEs (P = .0005), cutaneous irAEs (P = .0042), endocrine irAEs (P < .0001), gastrointestinal irAEs (P = .0391), and rheumatologic irAEs (P = .0086) were significantly related to progression-free survival. Any grade irAEs (P < .0001), single-site irAEs (P < .0001), multiple-site irAEs (P = .0003), cutaneous irAEs (P = .0002), endocrine irAEs (P = .0001), and rheumatologic irAEs (P = .0214) were significantly related to overall survival. CONCLUSIONS: This study confirms the feasibility and the safety of first-line, single-agent pembrolizumab, in a large, real-world cohort of patients with NSCLC with PD-L1 expression ≥ 50%. The occurrence of irAEs may be a surrogate of clinical activity and improved outcomes in this setting.
BACKGROUND: The role of immune-related adverse events (irAEs), as a surrogate predictor of the efficacy of checkpoint inhibitors, has not yet been described in the setting of first-line, single-agent pembrolizumab for patients with metastatic non-small-cell lung-cancer (NSCLC) with a programmed death-ligand 1 (PD-L1) expression of ≥ 50%. PATIENTS AND METHODS: We previously conducted a multicenter retrospective analysis in patients with treatment-naive metastatic NSCLC and a PD-L1 expression of ≥ 50% receiving first-line pembrolizumab. Here, we report the results of the irAE analysis and the potential correlation between irAEs and clinical outcomes. RESULTS: A total of 1010 patients were included in this analysis; after a 6-week landmark selection, 877 (86.8%) patients were included in the efficacy analysis. Any grade irAEs (P < .0001), grade 3/4 irAEs (P = .0025), leading to discontinuation irAEs (P = .0144), multiple-site and single-site irAEs (P < .0001), cutaneous irAEs (P = .0001), endocrine irAEs (P = .0227), pulmonary irAEs (P = .0479), and rheumatologic irAEs (P = .0018) were significantly related to a higher objective response rate. Any grade irAEs (P < .0001), single-site irAEs (P < .0001), multiple-site irAEs (P = .0005), cutaneous irAEs (P = .0042), endocrine irAEs (P < .0001), gastrointestinal irAEs (P = .0391), and rheumatologic irAEs (P = .0086) were significantly related to progression-free survival. Any grade irAEs (P < .0001), single-site irAEs (P < .0001), multiple-site irAEs (P = .0003), cutaneous irAEs (P = .0002), endocrine irAEs (P = .0001), and rheumatologic irAEs (P = .0214) were significantly related to overall survival. CONCLUSIONS: This study confirms the feasibility and the safety of first-line, single-agent pembrolizumab, in a large, real-world cohort of patients with NSCLC with PD-L1 expression ≥ 50%. The occurrence of irAEs may be a surrogate of clinical activity and improved outcomes in this setting.
Authors: Carlos Carvajal; Felipe González; Rafael Beltrán; Ricardo Buitrago; Amelia de Los Reyes; Augusto Llamas; Julián Beltrán; José Carreño Journal: Updates Surg Date: 2021-01-04
Authors: Marco Russano; Alessio Cortellini; Raffaele Giusti; Alessandro Russo; Federica Zoratto; Francesca Rastelli; Alain Gelibter; Rita Chiari; Olga Nigro; Michele De Tursi; Sergio Bracarda; Stefania Gori; Francesco Grossi; Melissa Bersanelli; Lorenzo Calvetti; Vincenzo Di Noia; Mario Scartozzi; Massimo Di Maio; Paolo Bossi; Alfredo Falcone; Fabrizio Citarella; Francesco Pantano; Corrado Ficorella; Marco Filetti; Vincenzo Adamo; Enzo Veltri; Federica Pergolesi; Mario Alberto Occhipinti; Linda Nicolardi; Alessandro Tuzi; Pietro Di Marino; Serena Macrini; Alessandro Inno; Michele Ghidini; Sebastiano Buti; Giuseppe Aprile; Eleonora Lai; Marco Audisio; Salvatore Intagliata; Riccardo Marconcini; Davide Brocco; Giampiero Porzio; Marta Piras; Erika Rijavec; Francesca Simionato; Clara Natoli; Marcello Tiseo; Bruno Vincenzi; Giuseppe Tonini; Daniele Santini Journal: Cancer Immunol Immunother Date: 2021-08-31 Impact factor: 6.968
Authors: Michael Zhang; Adrian J Rodrigues; Erqi L Pollom; Iris C Gibbs; Scott G Soltys; Steven L Hancock; Joel W Neal; Sukhmani K Padda; Kavitha J Ramchandran; Heather A Wakelee; Steven D Chang; Michael Lim; Melanie Hayden Gephart; Gordon Li Journal: J Neurooncol Date: 2021-01-07 Impact factor: 4.130
Authors: Alessio Cortellini; Biagio Ricciuti; Marcello Tiseo; Emilio Bria; Giuseppe L Banna; Joachim Gjv Aerts; Fausto Barbieri; Raffaele Giusti; Diego L Cortinovis; Maria R Migliorino; Annamaria Catino; Francesco Passiglia; Mariangela Torniai; Alessandro Morabito; Carlo Genova; Francesca Mazzoni; Vincenzo Di Noia; Diego Signorelli; Alain Gelibter; Mario Alberto Occhipinti; Francesca Rastelli; Rita Chiari; Danilo Rocco; Alessandro Inno; Michele De Tursi; Pietro Di Marino; Giovanni Mansueto; Federica Zoratto; Francesco Grossi; Marco Filetti; Pamela Pizzutilo; Marco Russano; Fabrizio Citarella; Luca Cantini; Giada Targato; Olga Nigro; Miriam G Ferrara; Sebastiano Buti; Simona Scodes; Lorenza Landi; Giorgia Guaitoli; Luigi Della Gravara; Fabrizio Tabbò; Serena Ricciardi; Alessandro De Toma; Alex Friedlaender; Fausto Petrelli; Alfredo Addeo; Giampiero Porzio; Corrado Ficorella Journal: J Immunother Cancer Date: 2020-10 Impact factor: 13.751