Impact of steroids indication on the efficacy of immunotherapy in a multi-tumor cohort of patients: Time and dose-dependent evaluation.

person Pablo Gajate Medical Oncology Department, University Hospital Ramón y Cajal, Madrid, Spain info_outline Pablo Gajate, Victor Albarrán, Patricia Guerrero, Coral García de Quevedo Suero, Carlos González, Jesús Chamorro, Diana I. Rosero, Jaime Moreno-Doval, Juan Carlos Calvo, Patricia Pérez de Aguado, Victor Alia, Pilar Sotoca, Ana Maria Barrill, Maria San Román, Ainara Soria Rivas, Maria Eugenia Olmedo Garcia, Cristina Saavedra Serrano, Alfonso Cortés Salgado, Federico Longo, Pilar Garrido

Authors person Pablo Gajate Medical Oncology Department, University Hospital Ramón y Cajal, Madrid, Spain info_outline Pablo Gajate, Victor Albarrán, Patricia Guerrero, Coral García de Quevedo Suero, Carlos González, Jesús Chamorro, Diana I. Rosero, Jaime Moreno-Doval, Juan Carlos Calvo, Patricia Pérez de Aguado, Victor Alia, Pilar Sotoca, Ana Maria Barrill, Maria San Román, Ainara Soria Rivas, Maria Eugenia Olmedo Garcia, Cristina Saavedra Serrano, Alfonso Cortés Salgado, Federico Longo, Pilar Garrido Organizations Medical Oncology Department, University Hospital Ramón y Cajal, Madrid, Spain, Medical Oncology Department, Ramón y Cajal University Hospital, Madrid, Spain, Hospital Universitario Ramón y Cajal, Madrid, Spain, Medical Oncology Department, Ramón y Cajal Hospital, Madrid, Spain, Medical Oncology Department. Hospital Universitario Ramón y Cajal, Madrid, Spain, Hospital Universitario de Ramon y Cajal, Madrid, Spain, Medical Oncology Departmente. Ramón y Cajal Hospital, Instituto Ramón y Cajal de Investigación Sanitaria (IRICYS), CIBERONC, Madrid, Spain, Medical Oncology Department, Hospital Ramón y Cajal, Universidad de Alcalá, Madrid, Spain Abstract Disclosures Research Funding No funding sources reported Background: The detrimental impact of steroids (ST) on patients receiving immune checkpoint inhibitors (ICI) has been described in several studies. However, the influence of indication, time of administration, and dosage is more controversial. Methods: This is a retrospective analysis of 475 patients with advanced solid tumors treated with ICI at a tertiary university hospital, between 2015 and 2022. Data related to baseline characteristics and clinical outcomes were collected. For each patient, the daily ST dose (equivalent in mg/kg of prednisone) and indication were registered until progression or death. We evaluated the impact of ST indication on the objective response rate (ORR) and progression-free survival (PFS). In addition, we analyzed the potential influence of cumulative dose (CD) (patients were divided into quartiles (Q) based on the total dose of steroids received throughout ICI treatment) and time of administration (30 days from C1 (D1-30), 3 months from C1 (D1-D90) and after 6 months (m) from C1 (>6m)). Results: We analyzed 475 pts with advanced solid tumors (NSCLC: 33.9%; urothelial: 17.3%; renal: 13.7%; melanoma: 11.2%; head and neck: 11.0%; others: 12.9%) treated with ICI (anti-PD1 [64.4%], anti-PDL1 [20.4%], anti-PD1 plus anti-CTLA4 [13.3%] or anti-CTLA4 [1.9%]). 49.5% of pts received ST during ICI treatment (20.6% due to an immune-related adverse event [irAE] and 33.9% with other indications). 24.2% of patients received ST in D1-30 (5.7% irAE vs 20.6% other indications), 32.6% in D1-D90 (10.7% vs 25.1%) and 17.1% in >6m (12% vs 8%). The ORR was significantly higher in pts who received ST for irAES than in those treated with ST for other reasons both in D1-30 (40% vs 15.3%; p = 0.028) and in D1-90 (42.6% vs 17%; p = 0.001). Furthermore, the ORR was very similar to that of patients who did not receive any ST treatment (40% vs 37.8% in D1-30, and 42.6% vs 37.7% in D1-90). There was an inverse correlation between the CD of ST in D1-30 and the ORR (37.78% [no steroids], 29.63% [Q1], 21.42% [Q2], 11.11% [Q3] and 22.22% [Q4]). However, this association was not observed among patients receiving ST for irAEs during D1-30 (37.8% [no steroids], 100% [Q1], 0% [Q2], 33.3% [Q3] and 42.9% [Q4]; p = 0.21) and in D1-90 (37.7% [no steroids], 0% [Q1], 41.7% [Q2], 42.9% [Q3] and 52.9% [Q4]; p = 0.29). Finally, among patients without progression after 6 months from C1, PFS tended to be longer in those exposed to ST. However, PFS was similar regardless of the reason for ST use. Conclusions: Exposure to ST is associated with poorer ICI outcomes. Our study showed that the impact of ST is time- and dose-dependent. Interestingly, these results were not observed among patients exposed to ST due to irAEs, suggesting that immune toxicity may attenuate ST detrimental effects.