‘Prudent’ corticosteroid use advised prior to anti-PD1, PD-L1 initiation
medwireNews: Corticosteroid use immediately prior to treatment with agents targeting programmed cell death protein 1 (PD-1) or its ligand (PD-L1) is associated with significantly reduced survival in patients with non-small-cell lung cancer (NSCLC), real-world study data show.
Therefore, “[p]rudent use of corticosteroids at the time of initiating PD-(L)1 blockade is recommended,” Matthew Hellmann (Memorial Sloan Kettering Cancer Center, New York, USA) and co-authors write in the Journal of Clinical Oncology.
The findings are based on a review of clinical and pharmacy records for 640 PD-1 and PD-L1–naïve patients with advanced NSCLC from two independent cohorts.
Of these, 90 (14%) were receiving corticosteroids of at least 10 mg of prednisone equivalent daily when they started treatment with a single-agent PD-1 or PD-L1 inhibitor.
The reasons for corticosteroid use were most commonly dyspnea (33%), fatigue (21%), and brain metastases (19%).
In both cohorts, baseline corticosteroid use of at least 10 mg of prednisone equivalent per day was associated with significantly shorter median progression-free survival (PFS) when compared with a lower dose or no corticosteroid use (1.9 vs 2.6 months in cohort 1 and 1.7 vs 1.8 months in cohort 2) as well as shorter median overall survival (OS; 5.4 vs 12.1 months and 3.3 vs 9.4 months).
In cohort 1 (n=455), baseline corticosteroid use was also associated with a significantly decreased objective response rate, at 6% versus 19%, but the difference did not reach statistical significance in cohort 2 (n=185; 8 vs 18%).
After adjustment for smoking history, performance status, and history of brain metastases, a multivariate analysis of the pooled population showed that baseline corticosteroid use was associated with a significant 31% increased risk for disease progression or death and a 66% increased risk for death.
The researchers note that the detrimental effects of corticosteroid use on outcome were similar when the daily dose was at or above 20 mg of prednisone equivalent or 10–19 mg compared with less than 10 mg, whereas they differed according to the timing of the treatment.
Specifically, patients who discontinued corticosteroids up to 30 days before PD-1 or PD-L1 inhibitor initiation had PFS and OS that was intermediate between those who were taking corticosteroids on the day that immune checkpoint blockade was initiated and those who received no corticosteroids within 30 days of the start of therapy.
Hellman and team say that corticosteroid use for the control of brain metastasis and improvement of fatigue, dyspnea, and anorexia is common in patients with NSCLC, but based on their findings, “it may be prudent to attempt to manage these symptoms with other pharmacologic and/or nonpharmacologic methods.”
They add: “These strategies could enable patients to be tapered off corticosteroids before the start of PD-(L)1 blockade to potentially achieve maximum benefit from these agents; however, of importance, medically necessary corticosteroids (eg, management of brain metastases) should not be avoided.”
By Laura Cowen
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