Immune Checkpoint Inhibitor Outcomes for Patients With Non–Small-Cell Lung Cancer Receiving Baseline Corticosteroids for Palliative Versus Nonpalliative Indications

Abstract

PURPOSE Baseline use of corticosteroids is associated with poor outcomes in patients with non–small-cell lung cancer (NSCLC) treated with programmed cell death-1 axis inhibition. To approach the question of causation versus correlation for this association, we examined outcomes in patients treated with immunotherapy depending on whether corticosteroids were administered for cancer-related palliative reasons or cancer-unrelated indications. PATIENTS AND METHODS Clinical outcomes in patients with NSCLC treated with immunotherapy who received ≥ 10 mg prednisone were compared with outcomes in patients who received 0 to < 10 mg of prednisone. RESULTS Of 650 patients, the 93 patients (14.3%) who received ≥ 10 mg of prednisone at the time of immunotherapy initiation had shorter median progression-free survival (mPFS) and median overall survival (mOS) times than patients who received 0 to < 10 mg of prednisone (mPFS, 2.0 v 3.4 months, respectively; P = .01; mOS, 4.9 v 11.2 months, respectively; P < .001). When analyzed by reason for corticosteroid administration, mPFS and mOS were significantly shorter only among patients who received ≥ 10 mg prednisone for palliative indications compared with patients who received ≥ 10 mg prednisone for cancer-unrelated reasons and with patients receiving 0 to < 10 mg of prednisone (mPFS, 1.4 v 4.6 v 3.4 months, respectively; log-rank P < .001 across the three groups; mOS, 2.2 v 10.7 v 11.2 months, respectively; log-rank P < .001 across the three groups). There was no significant difference in mPFS or mOS in patients receiving ≥ 10 mg of prednisone for cancer-unrelated indications compared with patients receiving 0 to < 10 mg of prednisone. CONCLUSION Although patients with NSCLC treated with ≥ 10 mg of prednisone at the time of immunotherapy initiation have worse outcomes than patients who received 0 to < 10 mg of prednisone, this difference seems to be driven by a poor-prognosis subgroup of patients who receive corticosteroids for palliative indications.

Association of Steroids Use with Survival in Patients Treated with Immune Checkpoint Inhibitors: A Systematic Review and Meta-Analysis

“…Conversely, the effect of steroids administered to mitigate AEs did not seem to negatively affect OS; this finding was similar in NSCLC and melanoma. Similar results were presented by Ricciuti et al, where steroids' detrimental effect appeared to be linked to the poor-prognosis subgroup of patients who received corticosteroids for palliative indications [22]. This may be associated with a larger number of patients with poor performance status or brain metastases where steroids are provided for cancer-related palliation.…”

“…In total, 346 potentially relevant citations were reviewed (Figure 1). Ultimately, 16 studies published from 2009 to 2019 that reported OS and/or PFS data were included in the final analysis [17,[19][20][21][22][27][28][29][30][31][32][33][34][35][36][37]. The total number of patients included was 4045 ranging from 45 to 1025 patients per study (median, 151).…”

“…Furthermore, a recent paper confirmed the worse outcomes in NSCLC patients treated with ICIs if doses ≥ 10 mg of prednisone equivalent were administered within 24 h of ICIs initiation. However, the detrimental corticosteroids effect was evident only in patients who were on steroids therapy because of cancer-related palliative indications; doses ≥ 10 mg of prednisone for cancer-unrelated indications, such as treatment of autoimmune disease, chronic obstructive pulmonary disease flare, and prophylaxis for hypersensitivity reactions, were not associated with worse outcomes in comparison with less than 10 mg of prednisone or no steroids administration [22].…”

Predictive factors for progression‐free survival in non‐small cell lung cancer patients receiving nivolumab based on performance status

“…These predictive factors for nivolumab response in patients with NSCLC, including PS, are consistent with those identified in previous reports. 3,10,[19][20][21][22][23][24] The factors associated with PFS in nivolumab-treated patients with NSCLC with good PS were similar to those identified in the entire cohort. Smoking has been reported to enhance tumor mutation burden; consistent with this finding, nivolumab is efficacious in smokers.…”

Current multidisciplinary management of brain metastases

“…17 Using the lowest effective dose minimizes steroidrelated toxicity but also may result in less suppression of immunotherapy effects. Conflicting data exist regarding whether all patients who receive ≥10 mg prednisone daily (or equivalent) at the initiation of single-agent, programmed cell death-1 (PD-1) or programmed death ligand 1 (PD-L1) inhibitors have worse OS and progression-free survival (PFS) compared with patients who require <10 mg. [18][19][20] Further investigation is necessary to determine the effects of corticosteroid use and their timing on the efficacy of immune checkpoint inhibition (ICI) therapy either alone or in conjunction with chemotherapy. Importantly, some patients who required corticosteroids in the aforementioned studies did demonstrate a response to ICI, so patients should not be excluded from immunotherapy if they are receiving corticosteroids.…”