LBA13 - 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)

P. Iyengar¹, Y. Cheng², D. Spigel³, B. C. Cho⁴, K. Laktionov⁵, Y. Chen⁶, K. H. Lee⁷, E. Buchmeier⁸, N. Villanueva Palicio⁹, I. Okamoto¹⁰, A. Badzio¹¹, A. SHI¹², S. Lu¹³, M. Özgüroglu¹⁴, Y. Ohe¹⁵, R. Bernabe¹⁶, B. Gill¹⁷, P. Chugh¹⁸, H. Gowda¹⁸, and S. Senan¹⁹; ¹Memorial Sloan Kettering Cancer Center, New York, NY, ²Jilin Cancer Hospital, Changchun, China, ³Sarah Cannon Research Institute, Nashville, TN, ⁴Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Korea, Republic of (South), ⁵Federal State Budgetary Institution “N.N. Blokhin National Medical Research Center of Oncology” of the Ministry of Health of the Russian Federation (N.N. Blokhin NMRCO), Moscow, Russian Federation, ⁶Cancer & Hematology Centers of Western Michigan, Grand Rapids, MI, ⁷Department of Internal Medicine, Chungbuk National University Hospital, Cheongju-Si, Korea, Republic of (South), ⁸Hospitals of the City of Cologne gGmbH, Cologne, Germany, ⁹Hospital Universitario Central de Asturias, Oviedo, Spain, ¹⁰Kyushu University Hospital, Fukuoka, Japan, ¹¹Medical University of Gdansk, Gdansk, Poland, ¹²12. Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Radiation Oncology, Peking University Cancer Hospital & Institute, Beijing, China, ¹³Shanghai Lung Cancer Centre, Shanghai Chest Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China, ¹⁴Istanbul University-Cerrahpasa, Cerrahpasa School of Medicine, Istanbul, Turkey, ¹⁵National Cancer Center Hospital, Tokyo, Japan, ¹⁶Hospital Universitario Virgen del Rocio, Seville, Spain, ¹⁷AstraZeneca, Mississauga, ON, Canada, ¹⁸AstraZeneca, Gaithersburg, MD, ¹⁹Amsterdam University Medical Centers, Vrije Universiteit Amsterdam, Cancer Center Amsterdam, Amsterdam, Netherlands

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. LBA 13 – Table 1

imAEs (grouped term) in =5 pts in either arm	D (n=262)				P (n=265)
	Any grade / grade 3/4, n	mTTO, days (range)	Resolved, n	mTTR, days (range)	Any grade / grade 3/4, n	mTTO, days (range)	Resolved, n	mTTR, days (range)
Any imAE	84 / 14	?	30	?	27 / 4	?	13	?
Pneumonitis	31 / 5	55 (1?375)	18	42.5 (9–379)	8 / 2	65.5 (24?124)	3	73 (67–73)
Hypothyroid	36 / 0	113 (28?534)	6	57.5 (29–197)	9 / 0	169 (56?391)	3	57 (28–84)
Hyperthyroid	5 / 0	27 (26?166)	5	64 (60–814)	1 / 0	1 (NA)	1	224 (NA)
Dermatitis/rash	5 / 1	218 (20?600)	2	51.5 (15–88)	0 / 0	NA	NA	NA
Diarrhea/colitis	2 / 2	471.5 (339?604)	0	NA	5 / 0	13 (2?463)	4	35.5 (10–106)