Giannis Mountzios1, Alessandro de Toma2, Panagiota Economopoulou3, Alex Friedlaender4, Marco Banini5, Giuseppe Lo Russo2, Panagiotis Baxevanos6, Fausto Roila5, Giuseppe Luigi Banna7, Athina Christopoulou8, Beatriz Jimenez9, Ana Collazo-Lorduy9, Helena Linardou10, Antonio Calles11, Domenico Galetta12, Alfredo Addeo4, Andrea Camerini13, Pamela Pizzutilo12, Paris Kosmidis14, Marina Chiara Garassino2, Claudia Proto2, Diego Signorelli2, Giulio Metro5. 1. Second Department of Medical Oncology and Clinical trials Unit, Henry Dunant Hospital Center, Athens, Greece. Electronic address: gmountzios@gmail.com. 2. Fondazione IRCCS, Istituto Nazionale Tumori di Milano, Milan, Italy. 3. Section of Medical Oncology, Second Department of Internal Medicine, Attikon University Hospital, Athens, Greece. 4. Oncology Department, Geneva University Hospital, Geneva, Switzerland. 5. S.C. Oncologia, Ospedale Santa Maria della Misericordia, Azienda Ospedaliera di Perugia, Perugia, Italy. 6. Second Department of Medical Oncology, Saint Savvas Anti-Cancer Hospital, Athens, Greece. 7. Department of Haematology/Oncology, Queen Alexandra Hospital, Portsmouth, United Kingdom. 8. Medical Oncology, Agios Andreas General Hospital of Patras, Patras, Greece. 9. Department of Medical Oncology, Hospital HM Sanchinarro, Madrid, Spain. 10. Fourth Oncology Department, Metropolitan Hospital, Athens, Greece. 11. Division of Medical Oncology, Hospital General Universitario Gregorio Marañón, Madrid, Spain. 12. Medical Thoracic Oncology Unit, IRCCS Istituto Tumori "Giovanni Paolo II," Bari, Italy. 13. U.O.C. Oncologia, Ospedale Versilia, Lido di Camaiore, Italy. 14. Second Department of Medical Oncology, Hygeia Hospital, Athens, Greece.
Abstract
BACKGROUND: Real-world data have suggested a detrimental effect of steroid use in patients with advanced non-small-cell lung cancer (NSCLC) receiving immunotherapy. However, previous studies included heterogeneous cohorts of patients receiving different lines of treatment with several immuno-oncology agents and various combinations of chemotherapy and immuno-oncology agents. PATIENTS AND METHODS: A comprehensive clinicopathologic database of patients with NSCLC and programmed cell death ligand 1 >50% treated with frontline pembrolizumab monotherapy was constructed in 14 centers in Italy, Spain, Greece, and Switzerland. A multivariate analysis adjusting for the established prognostic factors was performed using a Cox regression model. RESULTS: For the 265 eligible patients, the median age at diagnosis was 67 years, 66% were male, 90% were current or former smokers, 18% had had an Eastern Cooperative Oncology Group performance status of 2 or 3. Of the NSCLC subtypes, 64% were adenocarcinoma and 25% were squamous cell. Of the patients, 18% had had brain metastases at diagnosis and 24% had received steroids before or during pembrolizumab treatment. The median time to progression was 4.4 months with and 13.7 months without steroid use (hazard ratio [HR], 2.55; 95% confidence interval [CI], 1.69-3.85; log-rank P < .001). The median survival was 22.5 months for the whole cohort, 7.7 months for the steroid group, and not reached for the non-steroid group (HR, 3.64; 95% CI, 2.34-5.68; log-rank P < .001). On multivariate analysis accounting for all established prognostic variables, steroid use was still independently associated with a high risk of progression (HR, 1.864; 95% CI, 1.179-2.949; P = .008) and death (HR, 2.292; 95% CI, 1.441-3.644; P < .001) CONCLUSIONS: In patients with advanced NSCLC and programmed cell death ligand 1 expression > 50% receiving frontline pembrolizumab monotherapy, any use of steroids before or during treatment was associated with an 86% increase in the risk of progression and a 2.3-fold increase in the risk of death, even accounting for palliative indication-related bias, including the presence of central nervous system metastasis. The use of steroids for palliative indications should be restricted to absolutely necessary for patients receiving immuno-oncology monotherapy.
BACKGROUND: Real-world data have suggested a detrimental effect of steroid use in patients with advanced non-small-cell lung cancer (NSCLC) receiving immunotherapy. However, previous studies included heterogeneous cohorts of patients receiving different lines of treatment with several immuno-oncology agents and various combinations of chemotherapy and immuno-oncology agents. PATIENTS AND METHODS: A comprehensive clinicopathologic database of patients with NSCLC and programmed cell death ligand 1 >50% treated with frontline pembrolizumab monotherapy was constructed in 14 centers in Italy, Spain, Greece, and Switzerland. A multivariate analysis adjusting for the established prognostic factors was performed using a Cox regression model. RESULTS: For the 265 eligible patients, the median age at diagnosis was 67 years, 66% were male, 90% were current or former smokers, 18% had had an Eastern Cooperative Oncology Group performance status of 2 or 3. Of the NSCLC subtypes, 64% were adenocarcinoma and 25% were squamous cell. Of the patients, 18% had had brain metastases at diagnosis and 24% had received steroids before or during pembrolizumab treatment. The median time to progression was 4.4 months with and 13.7 months without steroid use (hazard ratio [HR], 2.55; 95% confidence interval [CI], 1.69-3.85; log-rank P < .001). The median survival was 22.5 months for the whole cohort, 7.7 months for the steroid group, and not reached for the non-steroid group (HR, 3.64; 95% CI, 2.34-5.68; log-rank P < .001). On multivariate analysis accounting for all established prognostic variables, steroid use was still independently associated with a high risk of progression (HR, 1.864; 95% CI, 1.179-2.949; P = .008) and death (HR, 2.292; 95% CI, 1.441-3.644; P < .001) CONCLUSIONS: In patients with advanced NSCLC and programmed cell death ligand 1 expression > 50% receiving frontline pembrolizumab monotherapy, any use of steroids before or during treatment was associated with an 86% increase in the risk of progression and a 2.3-fold increase in the risk of death, even accounting for palliative indication-related bias, including the presence of central nervous system metastasis. The use of steroids for palliative indications should be restricted to absolutely necessary for patients receiving immuno-oncology monotherapy.
Authors: M V Verschueren; C M Cramer- van der Welle; M Tonn; F M N H Schramel; B J M Peters; E M W van de Garde Journal: Sci Rep Date: 2021-12-02 Impact factor: 4.379
Authors: Andrea De Giglio; Alessandro Di Federico; Chiara Deiana; Biagio Ricciuti; Marta Brambilla; Giulio Metro Journal: Drugs Context Date: 2022-07-08