Corticosteroid use and its impact on the efficacy of immunotherapy in multiple tumor types.

Abstract

e14583 Background: Studies have suggested that concurrent corticosteroid use may decrease the efficacy of immunotherapy for cancer treatment, however, the data remains limited. The purpose of this study is to expand upon the previous literature to analyze the outcomes of patients with the following cancer sites: renal cell, lung, melanoma, urothelial, head and neck, hepatocellular, or breast cancer who received immunotherapy and steroids concurrently. Our primary objective was to analyze the overall survival (OS) and objective response rate (ORR) of patients receiving immunotherapy with corticosteroids compared to immunotherapy alone. Methods: A retrospective cohort study was conducted of patients receiving immunotherapy plus corticosteroids compared to immunotherapy alone using University of Texas Medical Branch patients. Patients receiving nivolumab, pembrolizumab, atezolizumab, ipilimumab, durvalumab, or avelumab between January 1, 2012-August 2020 with one of the following cancers were included in the analysis: Renal cell carcinoma, lung carcinoma, melanoma, urothelial carcinoma, head and neck carcinoma, hepatocellular carcinoma, and breast cancer carcinoma. The resulting sample was then separated into two arms. The experimental sample received any of the following steroids either as part of their therapeutic regimen or for symptom management and within 30 days of immunotherapy initiation or at any time during the immunotherapy regimen: dexamethasone, prednisone, methylprednisolone, or hydrocortisone. The control did not receive steroids within 30 days of initiation or during the course of their immunotherapy regimen. Weibull regression models were then constructed to compute hazard ratios for OS at 6 months, 12 months, and 3 years. ORR - complete and partial response, stable disease, and disease progression - between the two arms was assessed using a chi-squared test. Results: Two hundred and sixty patients met inclusion criteria. Of this, 164 received corticosteroids. Our sample was primarily male (70.38%), white (66.54%), and had 0-1 comorbidities (83.08%), lung cancer (45%), and metastases (81.92%). There was no significant difference between the two arms regarding sex, age, number of comorbidities, ECOG score, cancer type, or race. There was no statistically significant difference in OS between the experimental and control arm at 6 months (HR: 1.01; 95%CI 0.63-1.62), 12 months (1.02; 95% CI 0.69-1.51), or 3 years (1.06; 95% CI 0.79-1.42). There was no significant difference in ORR at 6 months between the two arms (2 = 6.3, p=0.178). Conclusions: There was no statistically significant difference in OS or PFS between the two study arms. This study suggests that corticosteroid use does not affect immunotherapy efficacy as previous literature suggests. Larger studies are needed to assess the impact of corticosteroids on immunotherapy efficacy in patients with cancer.

Neoadjuvant sintilimab in combination with concurrent chemoradiotherapy for locally advanced gastric or gastroesophageal junction adenocarcinoma: a single-arm phase 2 trial

“…Fourth, nab-paclitaxel does not require premedication with corticosteroids, which might be more suitable in the context of the unsure impact of corticosteroids in patients receiving immunotherapy. Although there is no compelling evidence that corticosteroids decrease the efficacy of immunotherapy 66 , corticosteroids and immunotherapy both influence the immune system in different ways 67 , and it was considered prudent when designing the trial to avoid that potential confounder.…”

Determinants of activity and efficacy of anti-PD1/PD-L1 therapy in patients with advanced solid tumors recruited in a clinical trials unit: a longitudinal prospective biomarker-based study

“…Several studies led to the conclusion that avoiding or delaying the use of corticosteroids may result in maximizing the potential treatment benefits of immunotherapy [12][13][14][15][16]. However, other evidences highlight that corticosteroids have no detrimental effect on immunotherapy and high doses of steroids might reflect poorer basal conditions (e.g., active brain metastases, concurrent diseases, larger tumor volume), ultimately responsible for the scarce outcomes with ICI [17,18]. In our study, systemic administration of corticosteroids during ICI was associated with better PFS, ORR and DCB at the univariate analysis but lost any significant effect when adjusting for other clinicopathological factors.…”

“…Additionally, the optimal metastatic therapeutic setting (earlier or further lines), the efficacy in immunepretreated patients, the effects of exposure to immediately previous or concurrent radiotherapy (RT), and the optimal duration of treatment remain questions unanswered. To note, the impact of systemic corticosteroids and exposure to antibiotic (ATB) therapy on response to ICI are another major concern, with only few and/or conflicting data being published so far [9][10][11][12][13][14][15][16][17][18]. Finally, easy-to-detect and relatively low cost prognostic predictors able to stratify patients for either ICI clinical trial inclusion or better tailoring of the treatment strategy are urgently needed and the LIPI score, based on a relative neutrophil count and LDH is a promising one, which merits further validation in a pan-cancer setting [19,20].…”

Dupilumab as a treatment for cutaneous immune-related adverse events induced by immune checkpoint inhibitors: A case series and review of the literature

“…Other studies suggest that there is no difference in OS and PFS between patients receiving immunotherapy plus steroids and patients receiving immunotherapy alone. 14 Dupilumab has been used off-label for pruritus, prurigo nodularis, and BP unrelated to ICIs and there are ongoing clinical trials studying these potential indications. Dupilumab has also been evaluated in 11 patients with ICI-induced BP [15][16][17][18] and in 2 patients with ICI-induced eczema 19 and was successful in all of them.…”

“…Other studies suggest that there is no difference in OS and PFS between patients receiving immunotherapy plus steroids and patients receiving immunotherapy alone. 14 …”