LBA81 - Durvalumab (D) as consolidation therapy in limited-stage SCLC (LS-SCLC): Outcomes by prior concurrent chemoradiotherapy (cCRT) regimen and prophylactic cranial irradiation (PCI) use in the ADRIATIC trial

Background

At the first interim analysis of the phase 3, double-blind, placebo (P)-controlled ADRIATIC trial (NCT03703297) consolidation D vs P significantly improved the dual primary endpoints of overall (OS) and progression-free (PFS) survival in patients (pts) with LS-SCLC who had not progressed after cCRT. We report data in prespecified subgroups defined by prior cCRT-related variables and PCI use.

Methods

cCRT comprised either once-daily (QD) or twice-daily (BID) thoracic radiotherapy (RT) and 3/4 cycles of platinum-etoposide chemotherapy (CT), ± PCI (investigator’s choice). Pts were randomised (1–42 days post cCRT) to D (n=264), D + tremelimumab (n=200; arm remains blinded), or P (n=266), stratified by disease stage and receipt of PCI.

Results

Consolidation D consistently improved OS and PFS vs P across subgroups; magnitude of benefit with D vs P varied between CT subgroups. OS and PFS were longer with both D and P in the BID compared to QD RT and PCI-yes compared to PCI-no subgroups, and with D but not P in the carboplatin compared to cisplatin CT subgroups. Multivariable analyses for OS and PFS are ongoing to explore subgroup interactions and account for some differences in pt characteristics. Rates of maximum grade 3-4 treatment-emergent adverse events (TEAEs) with D vs P were 18.8% vs 22.8% in the BID and 26.4% vs 24.7% in the QD RT subgroups, 31.5% vs 31.8% in the carboplatin and 20.8% vs 20.3% in the cisplatin CT subgroups, and 28.4% vs 29.6% in PCI-yes and 19.8% vs 17.9% in PCI-no pts. Rates of TEAEs leading to D or P discontinuation were 17.4% vs 6.3% in the BID and 16.1% vs 12.4% in the QD RT subgroups, 16.9% vs 10.2% in the carboplatin and 16.2% vs 10.7% in the cisplatin CT subgroups, and 17.0% vs 15.5% in PCI-yes and 15.7% vs 4.9% in PCI-no pts.Table: LBA81

Conclusions

D demonstrated benefit vs P irrespective of prior cCRT components and PCI use, supporting consolidation D as a new standard of care in LS-SCLC.

Clinical trial identification

NCT03703297 (release date: 27 September 2018).

Editorial acknowledgement

Medical writing support for this abstract, under the direction of the authors, was provided by Samantha Holmes and Steve Hill of Ashfield MedComms, an Inizio company, and was funded by AstraZeneca.

Legal entity responsible for the study

AstraZeneca.

Funding

AstraZeneca.

Disclosure

S. Senan: Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Advisory Role: MSD; Other, Personal, Coordinating PI: AstraZeneca; Financial Interests, Personal, Invited Speaker: MSD, AstraZeneca; Financial Interests, Institutional, Research Funding: AstraZeneca, BMS. D.R. Spigel: Financial Interests, Institutional, Advisory Role: AbbVie, Amgen, AstraZeneca, Bristol Myers Squibb, Genentech/Roche, GSK, Ipsen, Jazz Pharmaceuticals, Lyell Immunopharma, MedImmune, Monte Rosa Therapeutics, Novartis, Novocure, Sanofi/Aventis; Financial Interests, Institutional, Research Funding: AbbVie, Aeglea Biotherapeutics, Agios, Amgen, Anheart Therapeutics, Apollomics, Arcus Biosciences, Arrys Therapeutics, Ascendis Pharma, Asher Biotherapeutics, Astellas Pharma, AstraZeneca, Bayer, BeiGene, BioNTech, Blueprint Medicines, Boehringer Ingelhei, EMD Serono, Endeavor BioMedicines, Erasca, Inc, Evelo Biosciences, Faeth Therapeutics, Foundation Bio, Fujifilm, G1 Therapeutics, Genentech/Roche, Gilead Sciences, GSK, GRAIL, Hutchison MediPharma, ImClone Systems, Immunogen, Incyte, Ipsen, Ja, MedImmune, Merck, Millennium, Moderna Therapeutics, Monte Rosa Therapeutics, Nektar, Neon Therapeutics, Novartis, Novocure, Oncologie, Peloton Therapeutics, Pfizer, Phanes Therapeutics, PTC Therapeutics, PureTech, Razor Genomics, Repare Therapeutics, Rgen, Tarveda Therapeutics, Tesaro, Tizona Therapeutics, Inc., Transgene, University of Texas Southwestern Medical Center - Simmons Cancer Center, Verastem, Zai Lab; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: AstraZeneca; Genentech; Novartis. 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ASEICA (Spanish Association of Cancer Research ): ASEICA; Financial Interests, Other, Foundation president: ONCOSUR; Financial Interests, Other, member: Small Lung Cancer Group; Non-Financial Interests, Other, Board member of this anti-cancer Charity: AECC; Non-Financial Interests, Member, Past-President: ASEICA (Spanish Cancer Research Association); Non-Financial Interests, Leadership Role, President: Oncosur Foundation. L. Szadkowski: Financial Interests, Personal, Full or part-time Employment: AstraZeneca. P. Chugh: Financial Interests, Personal, Full or part-time Employment: AstraZeneca. W.C.V. Lai: Financial Interests, Personal, Full or part-time Employment: AstraZeneca; Financial Interests, Personal, Stocks/Shares: AstraZeneca. All other authors have declared no conflicts of interest.