Alessio Cortellini1,2, Marcello Tiseo3,4, Giuseppe L Banna5, Federico Cappuzzo6, Joachim G J V Aerts7, Fausto Barbieri8, Raffaele Giusti9, Emilio Bria10,11, Diego Cortinovis12, Francesco Grossi13, Maria R Migliorino14, Domenico Galetta15, Francesco Passiglia16, Daniele Santini17, Rossana Berardi18, Alessandro Morabito19, Carlo Genova20, Francesca Mazzoni21, Vincenzo Di Noia22, Diego Signorelli23, Alessandro Tuzi24, Alain Gelibter25, Paolo Marchetti9,25,26, Marianna Macerelli27, Francesca Rastelli28, Rita Chiari29, Danilo Rocco30, Stefania Gori31, Michele De Tursi32, Giovanni Mansueto33, Federica Zoratto34, Matteo Santoni35, Marianna Tudini36, Erika Rijavec13, Marco Filetti9, Annamaria Catino15, Pamela Pizzutilo15, Luca Sala12, Fabrizio Citarella17, Russano Marco17, Mariangela Torniai18, Luca Cantini7,18, Giada Targato27, Vincenzo Sforza19, Olga Nigro24, Miriam G Ferrara10,11, Ettore D'Argento10, Sebastiano Buti3, Paola Bordi3, Lorenzo Antonuzzo21, Simona Scodes6, Lorenza Landi6, Giorgia Guaitoli8, Cinzia Baldessari8, Luigi Della Gravara30, Maria Giovanna Dal Bello20, Robert A Belderbos7, Paolo Bironzo16, Simona Carnio16, Serena Ricciardi14, Alessio Grieco14, Alessandro De Toma23, Claudia Proto23, Alex Friedlaender37, Ornella Cantale5, Biagio Ricciuti38,39, Alfredo Addeo37, Giulio Metro40, Corrado Ficorella41,42, Giampiero Porzio41,42. 1. Medical Oncology, St. Salvatore Hospital, L'Aquila, Italy. alessiocortellini@gmail.com. 2. Department of Biotechnological and Applied Clinical Sciences, University of L'Aquila, Via Vetoio, 67100, L'Aquila, Italy. alessiocortellini@gmail.com. 3. Medical Oncology Unit, University Hospital of Parma, Parma, Italy. 4. Department of Medicine and Surgery, University of Parma, Parma, Italy. 5. Oncology Department, United Lincolnshire Hospital NHS Trust, Lincoln, UK. 6. Department of Oncology and Hematology, AUSL Romagna, Ravenna, Italy. 7. Department of Pulmonary Diseases, Erasmus Medical Center, Rotterdam, The Netherlands. 8. Department of Oncology and Hematology, Modena University Hospital, Modena, Italy. 9. Medical Oncology Unit, Sant' Andrea Hospital fo Rome, Rome, Italy. 10. Comprehensive Cancer Center, Fondazione Policlinico Universitario "A. Gemelli" IRCCS, Rome, Italy. 11. Department of Translational Medicine and Surgery, Università Cattolica del Sacro Cuore, Rome, Italy. 12. Medical Oncology, Ospedale San Gerardo, Monza, Italy. 13. Medical Oncology Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy. 14. Pneumo-Oncology Unit, St. Camillo-Forlanini Hospital, Rome, Italy. 15. Thoracic Oncology Unit, Clinical Cancer Center, IRCCS Istituto Tumori "Giovanni Paolo II", Bari, Italy. 16. Department of Oncology, San Luigi Gonzaga Hospital, University of Turin, Orbassano, TO, Italy. 17. Medical Oncology, Campus Bio-Medico University, Rome, Italy. 18. Oncology Clinic, Ospedali Riuniti Di Ancona, Università Politecnica Delle Marche, Ancona, Italy. 19. Thoracic Medical Oncology, Istituto Nazionale Tumori 'Fondazione G Pascale', IRCCS, Naples, Italy. 20. Lung Cancer Unit, IRCCS Ospedale Policlinico San Martino, Genoa, Italy. 21. Department of Oncology, Careggi University Hospital, Florence, Italy. 22. Medical Oncology, University Hospital of Foggia, Foggia, Italy. 23. Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy. 24. Medical Oncology, ASST-Sette Laghi, Varese, Italy. 25. Medical Oncology (B), Policlinico Umberto I, "Sapienza" University of Rome, Rome, Italy. 26. Department of Clinical and Molecular Medicine, "Sapienza" University of Rome, Rome, Italy. 27. Department of Oncology, University Hospital Santa Maria Della Misericordia, Udine, Italy. 28. Medical Oncology, Fermo Area Vasta 4, Fermo, Italy. 29. Medical Oncology, Ospedali Riuniti Padova Sud "Madre Teresa Di Calcutta", Monselice, Italy. 30. Pneumo-Oncology Unit, Monaldi Hospital, Naples, Italy. 31. Oncology Unit, IRCCS Ospedale Sacro Cuore Don Calabria, Negrar, VR, Italy. 32. Department of Medical, Oral and Biotechnological Sciences, University G. D'Annunzio, Chieti-Pescara, Chieti, Italy. 33. Medical Oncology, F. Spaziani Hospital, Frosinone, Italy. 34. Medical Oncology, Santa Maria Goretti Hospital, Latina, Italy. 35. Department of Oncology, Macerata Hospital, Macerata, Italy. 36. Medical Oncology, AV2 Fabriano ASUR Marche, Fabriano, Italy. 37. Oncology Department, University Hospital of Geneva, Geneva, Switzerland. 38. Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA. 39. Division of Medical Oncology, S.Orsola-Malpighi Hospital, University of Bologna, 40138, Bologna, Italy. 40. Department of Medical Oncology, Santa Maria della Misericordia Hospital, Azienda Ospedaliera di Perugia, Perugia, Italy. 41. Medical Oncology, St. Salvatore Hospital, L'Aquila, Italy. 42. Department of Biotechnological and Applied Clinical Sciences, University of L'Aquila, Via Vetoio, 67100, L'Aquila, Italy.
Abstract
BACKGROUND: 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%. METHODS: We conducted a multicenter retrospective study aimed at evaluating the clinicopathologic correlates of pembrolizumab effectiveness in patients with treatment-naïve NSCLC and a PD-L1 expression of ≥ 50%. RESULTS: 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 < 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. CONCLUSION: Pembrolizumab was effective in a large cohort of NSCLC patients treated outside of clinical trials. Questions regarding the effectiveness in clinical subgroups, such as patients with poorer PS and with liver/bone metastases, still remain to be addressed. 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.
BACKGROUND: 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%. METHODS: We conducted a multicenter retrospective study aimed at evaluating the clinicopathologic correlates of pembrolizumab effectiveness in patients with treatment-naïve NSCLC and a PD-L1 expression of ≥ 50%. RESULTS: 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 < 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. CONCLUSION:Pembrolizumab was effective in a large cohort of NSCLCpatients treated outside of clinical trials. Questions regarding the effectiveness in clinical subgroups, such as patients with poorer PS and with liver/bone metastases, still remain to be addressed. 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.
Entities:
Keywords:
Bone metastases; Liver metastases; PD-L1; Performance status; Radiotherapy; Smoking status
Authors: Angel Qin; Songzhu Zhao; Abdul Miah; Lai Wei; Sandipkumar Patel; Andrew Johns; Madison Grogan; Erin M Bertino; Kai He; Peter G Shields; Gregory P Kalemkerian; Shirish M Gadgeel; Nithya Ramnath; Bryan J Schneider; Khaled A Hassan; Nicholas Szerlip; Zoey Chopra; Sara Journey; Jessica Waninger; Daniel Spakowicz; David P Carbone; Carolyn J Presley; Gregory A Otterson; Michael D Green; Dwight H Owen Journal: J Natl Compr Canc Netw Date: 2021-04-20 Impact factor: 12.693
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
Authors: Alessio Cortellini; Andrea De Giglio; Katia Cannita; Diego L Cortinovis; Robin Cornelissen; Cinzia Baldessari; Raffaele Giusti; Ettore D'Argento; Francesco Grossi; Matteo Santoni; Annamaria Catino; Rossana Berardi; Vincenzo Sforza; Giovanni Rossi; Lorenzo Antonuzzo; Vincenzo Di Noia; Diego Signorelli; Alain Gelibter; Mario Alberto Occhipinti; Alessandro Follador; Francesca Rastelli; Rita Chiari; Luigi Della Gravara; Alessandro Inno; Michele De Tursi; Pietro Di Marino; Giovanni Mansueto; Federica Zoratto; Marco Filetti; Michele Montrone; Fabrizio Citarella; Maria Vittoria Pensieri; Marco Russano; Luca Cantini; Olga Nigro; Alessandro Leonetti; Paola Bordi; Gabriele Minuti; Lorenza Landi; Alessandro De Toma; Clelia Donisi; Serena Ricciardi; Maria Rita Migliorino; Valerio Maria Napoli; Gianmarco Leone; Giulio Metro; Giuseppe L Banna; Alex Friedlaender; Alfredo Addeo; Corrado Ficorella; Giampiero Porzio Journal: Thorac Cancer Date: 2021-02-01 Impact factor: 3.500