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. B.C. Cho: Financial Interests, Personal, Advisory Board: Kanaph Therapeutic Inc, Bridgebio Therapeutics, Cyrus Therapeutics, Guardant Health, Oscotec Inc, J INTS Bio, Therapex Co., Ltd, Gliead, Amgen; Financial Interests, Personal, Full or part-time Employment: Yonsei University Health System; Financial Interests, Personal, Invited Speaker: AstraZeneca, Guardant, Roche, Korean Cancer Association, Korean Society of Medical Onoclogy, Korean Society of Thyroid-Head and Neck Surgery, Korean Cancer Study Group, Novartis, MSD, The Chinese Thoracic Oncology Society, Pfizer; Financial Interests, Personal, Member of Board of Directors: J INTS Bio; Financial Interests, Institutional, Research Funding: MOGAM Institute, LG Chem, Oscotec, Interpark Bio Convergence Corp, GIInnovation, GI-Cell, Abion, AbbVie, AstraZeneca, Bayer, Blueprint Medicines, Boehringer Ingelheim, Champions Oncology, CJ bioscience, CJ Blossom Park, Cyrus, Dizal Pharma, Genexine, Janssen, Lilly, MSD, Novartis, Nuvalent, Oncternal, Ono, Regeneron, Dong-A ST, Bridgebio therapeutics, Yuhan, ImmuneOncia, Illumina, Kanaph therapeutics, Therapex, JINTSbio, Hanmi, CHA Bundang Medical Center, Vertical Bio AG; Financial Interests, Personal, Royalties: Champions Oncology, Crown Bioscience, Imagen, PearlRiver Bio GmbH; Financial Interests, Personal, Speaker, Consultant, Advisor: Abion, BeiGene, Novartis, AstraZeneca, Boehringer Ingelheim, Roche, BMS, CJ, CureLogen, Cyrus therapeutics, Ono, Onegene Biotechnology, Yuhan, Pfizer, Eli Lilly, GI-Cell, Guardant, HK Inno-N, Imnewrun Biosciences Inc., Janssen, Takeda, MSD, Janssen, Medpacto, Blueprint medicines, RandBio, Hanmi; Financial Interests, Personal, Stocks/Shares: TheraCanVac Inc, Gencurix Inc, Bridgebio therapeutics, Kanaph Therapeutic Inc, Cyrus therapeutics, Interpark Bio Convergence Corp., J INTS BI; Financial Interests, Personal, Other, Founder: Daan Biotherapeutics. K. Laktionov: Financial Interests, Personal, Advisory Role: AstraZeneca, Roche AG, Biocad, Pfizer, Amgen; Financial Interests, Personal, Speaker’s Bureau: AstraZeneca, Roche AG, Biocad, Pfizer, Amgen, Swixx BioPharma. Y. Zenke: Financial Interests, Institutional, Local PI: AstraZeneca, GSK, Giliead Science, Merck, MSD, Daiichi Sankyo, Amgen; Financial Interests, Personal, Speaker’s Bureau: AstraZeneca, Lilly, Chugai, Ono, Bristol-Meyers Squibb, Takeda, Boheringer-Ingelheim, Taiho, MSD, Novartis, Pfizer, Nihon Kayaku, Kyowa Kirin,Amgen, Daiichi Sankyo. K.H. Lee: Financial Interests, Personal, Advisory Role: Bristol Myers Squibb, Pfizer, MSD, AstraZeneca, Eli-Lilly, Yuhan; Financial Interests, Personal, Research Funding: Merck. A.F. Navarro Mendivil: Financial Interests, Personal, Advisory Board: Boehringer Ingelheim, Oryzon Genomics, Amgen, Hengenix Biotech, MedSIR, BMS; Financial Interests, Personal, Invited Speaker: Roche, AstraZeneca, Pfizer, Takeda, Tecnofarma; Non-Financial Interests, Principal Investigator: BMS, PharmaMar, MSD, Amgen, Novartis, Debiopharm, Daichii Sankyo, Roche, AstraZeneca. E.L. Buchmeier: Financial Interests, Personal, Advisory Board: AstraZeneca, Janssen, BMS; Financial Interests, Personal, Funding: Janssen, AstraZeneca; Financial Interests, Institutional, Local PI: Janssen, BMS, AstraZeneca, Novartis, Gilead, MSD. S. Sezgin Goksu: Financial Interests, Personal, Advisory Board: Novartis, Pfizer; Financial Interests, Personal, Invited Speaker: Astellas, AstraZeneca, Novartis; Financial Interests, Personal, Principal Investigator: AstraZeneca, MSD, BMS, Novartis, Roche. A. Badzio: Financial Interests, Personal, Coordinating PI: AstraZeneca, Roche; Financial Interests, Personal, Invited Speaker: AstraZeneca, MSD; Financial Interests, Personal and Institutional, Local PI: AstraZeneca, Roche. D.B. Daniel: Non-Financial Interests, Personal, Principal Investigator: AstraZeneca, Novartis, Mirati, Genetech, Daiichi, GSK, Array, Merck, Amgen; Financial Interests, Institutional, Research Funding: AstraZeneca, Novartis, Mirati, Genetech, Daiichi, GSK, Array, Merck, Amgen. M. Zemanova: Financial Interests, Personal, Advisory Board: F. Hoffmann-La Roche, Sanofi; Financial Interests, Personal, Advisory Role: Bristol Myers Squibb; Financial Interests, Personal, Financially compensated role: AstraZeneca, Merck Sharp & Dohme; Financial Interests, Personal, Invited Speaker: AstraZeneca; Financial Interests, Personal, Principal Investigator: AstraZeneca, Bristol Myers Squibb, Daiichi Sankyo, Merck Sharp & Dohme, Novartis, Pfizer; Financial Interests, Personal, Speaker, Consultant, Advisor: Merck Sharp & Dohme. P. Iyengar: Financial Interests, Personal, Advisory Board: AstraZeneca, Novocure; Financial Interests, Institutional, Research Funding: Incyte. L.G. Paz-Ares: Financial Interests, Personal, Advisory Board, Speaker fees: Roche, MSD, BMS, AZ, Lilly, PharmaMar, BeiGene, Daichii, Medscape, PER; Financial Interests, Personal, Advisory Board: Merck Serono, Pfizer, Bayer, Amgen, Janssen, GSK, Novartis, Takeda, Sanofi, Mirati, Boehringer; Financial Interests, Personal, Other, Board member: Genomica, Altum sequencing; Financial Interests, Personal, Other, lectures: AICME; Financial Interests, Personal, Other, Lectures: CCO; Financial Interests, Personal, Member of Board of Directors, Board member: Stab Therapeutics; Financial Interests, Personal, Other, spinn off (I have arounfd 8% of stocks): Altum sequencing; Financial Interests, Personal, Ownership Interest, spin-off (10%): Stab Therapeutics; Financial Interests, Institutional, Coordinating PI: Daiichi Sankyo, AstraZeneca, Merck Sharp & Dohme corp, BMS, Janssen-Cilag international NV, Novartis, Roche, Sanofi, Tesaro, Alkermes, Lilly, Takeda, Pfizer, PharmaMar; Financial Interests, Personal, Coordinating PI: Amgen; Financial Interests, Other, Member: AACR, ASCO, ESMO; Financial Interests, Other, Foundation Board Member: AECC; Financial Interests, Other, President. 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.