Association of baseline systemic corticosteroid use with overall survival and time to next treatment in patients receiving immune checkpoint inhibitor therapy in real-world US oncology practice for advanced non-small cell lung cancer, melanoma, or urothelial carcinoma

Abstract

Immune checkpoint inhibitors (CPIs) have expanded treatment options for patients with solid tumors. Systemic corticosteroids (CSs) have an indispensable role in cancer care, but CS-related immunosuppression may counteract the CPI-driven antitumor immune response. This retrospective study investigated the association between baseline CS use (bCS; ≤14 days before, ≤30 days after CPI initiation) and clinical outcomes in patients with advanced non-small cell lung cancer (aNSCLC), melanoma (aMel), or urothelial carcinoma (aUC). We analyzed data from the Flatiron Health electronic health record–derived de-identified database for adults diagnosed with aNSCLC, aMel, or aUC between January 2011 and June 2017 who received ≥1 CPI monotherapy in any treatment line. Associations of bCS use with overall survival (OS) and time to next treatment (TTNT) were estimated using multivariable Cox proportional hazards models adjusting for demographic and clinical characteristics (i.e., ECOG performance status, site of metastases). In total, 2,213 patients were diagnosed with aNSCLC (n = 862), aMel (n = 742), or aUC (n = 609) and received ≥1 CPI administration. Most patients (67%-95%) received CSs, many during the baseline period (19%-30%). Patients with bCS use had shorter median OS than those with no bCS use for aNSCLC (6.6 vs 10.6 months; P = .00018), aMel (16.4 vs 21.5; P = .095), and aUC (4.1 vs 7.7; P = .0012). bCS use was associated with shorter OS (not significant for aMel) and TTNT in adjusted multivariable analyses, and clinical outcomes were not explained by prior CS use or other measured confounders. These findings suggest a potential association between bCS use and decreased CPI effectiveness, warranting further investigation.

Immunotherapy use outside clinical trial populations: never say never?

“…Additionally, patients with AID often require immunosuppressive treatment, which may compromise ICI efficacy. 4 Regarding the efficacy and overall toxicity of ICI in the AID population, in the first retrospective study of anti-PD-1 in AIDs, the objective response rate (ORR) was 33% in patients with melanoma, AID flares were common at 38% (6% grade 3) but otherwise 'conventional' irAEs occurred at rates similar to those previously reported in clinical studies (29% overall, 10% grade 3). 5 Subsequent retrospective studies of agents blocking PD-1 or its ligand (PD-L1) [primarily in melanoma and non-small-cell lung cancer (NSCLC)] reported similar findings (ORR: 22%-54%; AID flares: 6%-42%; irAEs: 16%-38%).…”

Association of Systemic Steroid Treatment and Outcome in Patients Treated with Immune Checkpoint Inhibitors: A Real-World Analysis

“…Importantly, this association was confirmed in a multivariate analysis, and to our knowledge this is the first study to indicate that the development of irAEs treated with steroids represents an independent predictor of ICIs’ efficacy. Intriguingly, a potential association with better prognosis in patients reporting irAEs has been previously described [ 34 , 35 , 36 ], thus balancing the immunosuppressive effect of steroid use. This is an important message to clinical oncologists, underlying the relevance of a rapid and appropriate steroid treatment in patients who experience irAEs precisely due to their better prognosis.…”

Impact of corticosteroid use on outcomes of non–small‐cell lung cancer patients treated with immune checkpoint inhibitors: A systematic review and meta‐analysis

“…In total, 11 studies reported the OSs following corticosteroid administration of patients with NSCLC under ICI therapy 11‐13,18‐20,22–26 . The pooled HR was 1.82 (95% CI, 1.51–2.18), indicating that the patients receiving corticosteroid therapy have significantly worse survivals than those not receiving corticosteroid therapy (Figure 2).…”