Safety Profile of Durvalumab (D) as Consolidation Treatment (tx) in Limited-Stage Small-Cell Lung Cancer (LS-SCLC) in ADRIATIC: Focus on Pneumonitis and Immune-Mediated Adverse Events (imAEs)

Purpose/Objective(s)

In the phase 3 ADRIATIC study (NCT03703297) in patients (pts) with LS-SCLC without progression after concurrent chemoradiotherapy (cCRT), D as consolidation tx significantly improved OS and PFS vs placebo (P) at the first planned interim analysis. D was well tolerated and AEs were consistent with the known safety profile. Here we present pneumonitis/radiation pneumonitis and imAEs.

Materials/Methods

530 eligible pts with stage I–III LS-SCLC (stage I/II inoperable), WHO PS 0/1, and no progression after cCRT, were randomized 1–42 days after cCRT to D 1500 mg or P every 4 weeks until investigator-determined progression or intolerable toxicity, or for a maximum of 24 months. Safety was a secondary endpoint. Given the similar clinical presentation of pneumonitis resulting from prior RT (radiation pneumonitis) or immunotherapy (immune-mediated pneumonitis), these events were analyzed as a grouped term to better estimate their frequency. imAEs were also assessed.

Results

262 pts received D and 265 received P. Pneumonitis/radiation pneumonitis (preferred terms of immune-mediated lung disease, interstitial lung disease, pneumonitis, radiation fibrosis–lung, and radiation pneumonitis) occurred in 38% (n=100) vs 30% (n=80) of pts in the D vs P arm (maximum grade 3/4 3% vs 3%; grade 5 0.4% vs 0%; leading to tx discontinuation 9% vs 3%). Median time from first study drug dose to onset (mTTO) of pneumonitis/radiation pneumonitis was 56 days (range 1–594) vs 56 days (2–228) in the D vs P arm; 40/100 events in the D arm and 23/80 in the P arm had resolved at data cutoff (Jan 15, 2024). imAEs occurred in 32% vs 10% of pts in the D vs P arm (maximum grade 3/4 5% vs 2%; grade 5 0.4% vs 0%; leading to tx discontinuation 7% vs 3%). 14% vs 6% of pts in the D vs P arms received high-dose steroids and 1% vs 0.4% received immunosuppressants to manage imAEs. The table shows mTTO, resolution, and median time to resolution (mTTR) for the most common imAEs.

Conclusion

In ADRIATIC, pneumonitis/radiation pneumonitis was common in both arms in this population who had received prior RT, and imAEs were as expected in the D arm; these events were mainly low grade and led to low rates of tx discontinuation, supporting the favorable benefit-risk profile for consolidation D after cCRT in LS-SCLC.