Three versus six weeks of corticosteroids for mild immune-related pneumonitis: a randomized trial

Abstract Rationale Optimal corticosteroid treatment duration for immune checkpoint inhibitor (ICI)–related pneumonitis remains uncertain. No randomized trials have addressed this issue. Objectives To determine whether a 3-week corticosteroid taper is noninferior to the guideline-recommended 6-week taper for short-term treatment success in patients with mild (Common Terminology Criteria for Adverse Events grade 1-2) immune-related pneumonitis. Methods Patients with mild immune-related pneumonitis were assigned to either a 3-week or 6-week corticosteroid regimen. The primary endpoint was the treatment success rate at 8 weeks, defined as resting room-air SpO2 ≥ 90% without steroid escalation or prolongation due to pneumonitis worsening. Measurements and main results Overall, 106 patients were randomly assigned (median age = 72 years; grade 2, 73%). Treatment success rates were 66.7% and 85.2% in the 3- and 6-week groups, respectively, which did not demonstrate noninferiority (difference = −18.5 percentage points; 80% CI, −29.0% to −7.9%; P = .621) of the 3-week regimen. A predefined exploratory analysis indicated superiority of the 6-week regimen (P = .013). Grade ≥3 adverse events occurred in 12% and 24% of the 3- and 6-week groups, respectively; however, all were manageable with clinical interventions. The total quality of life mean change using the King’s Brief Interstitial Lung Disease score from baseline was 4.78 and 6.28 in the 3- and 6-week groups, respectively (between-group difference = −1.50 percentage points; 95% confidence interval, −5.91 to 2.91). Overall survival was comparable between the groups (hazard ratio = 1.03; 95% CI, 0.46-2.29; P = .95). Conclusions This study establishes the 6-week corticosteroid regimen as an evidence-based standard for treating ICI-related pneumonitis.