297MO - Patterns of disease progression with durvalumab (D) after concurrent chemoradiotherapy (cCRT) in limited-stage small-cell lung cancer (LS-SCLC): Results from ADRIATIC

Background

At the first planned interim analysis of the phase III ADRIATIC study, D consolidation significantly improved overall and progression-free survival vs placebo (P), in patients (pts) with LS-SCLC and no progression after cCRT. We report exploratory analyses to characterise patterns of disease progression.

Methods

Pts with stage I–III LS-SCLC (stage I/II inoperable) and no progression after cCRT were randomised to D, D + tremelimumab (arm still blinded), or P, stratified by disease stage and prophylactic cranial irradiation (PCI) use. First site of progression (RECIST 1.1 by BICR) was classified as intrathoracic (IT; any lesion within lungs) and/or extrathoracic (ET; lesions outside the lung, including chest wall/diaphragm). Pts with only IT progression were censored in time to ET progression or death analyses and vice versa. In time to progression to brain/CNS or death analyses, pts with ET progression in other locations only or IT progression only were censored.

Results

At data cutoff (15 Jan 2024), 139/264 (52.7%) and 169/266 (63.5%) pts in the D and P arms, respectively, had progression or death. Time to IT progression or death and ET progression or death were prolonged with D vs P (Table). The rate of IT progression was similar with D and P but ET progression was lower with D. ET lesions at first progression occurred in 19.7% vs 29.7% of pts in the D and P arms, respectively, and mostly in a single organ (18.9% vs 28.6%); the most common site was the brain/CNS (6.8% vs 12.4%). Rates of first progression with brain/CNS metastases were lower with D vs P for pts who received PCI (2.8% [4/142] vs 6.3% [9/143]) and no PCI (11.5% [14/122] vs 19.5% [24/123]). Time to brain/CNS metastases or death is in the table.Table 297M0

NR, not reached; PD, progression; PFS, progression-free survival.

Counted in both time to IT and ET PD.

By Kaplan–Meier.

Conclusions

Findings suggest D consolidation reduced the rate of ET metastases and prolonged time to progression or death for IT and ET metastases, including brain/CNS metastases. D reduced brain/CNS metastases regardless of PCI use.

Clinical trial identification

NCT03703297.

Editorial acknowledgement

Medical writing support for the development of the abstract, under the direction of the authors, was provided by Connor Keating of Ashfield MedComms (Manchester, UK) an Inizio company, and funded by AstraZeneca.

Legal entity responsible for the study

AstraZeneca.

Funding

AstraZeneca.

Disclosure

S. Senan: Financial Interests, Personal, Advisory Board: AstraZeneca, MSD; Non-Financial Interests, Personal, Principal Investigator: AstraZeneca; Financial Interests, Personal, Invited Speaker: MSD, AstraZeneca; Financial Interests, Personal, Officer: ETOP IBCSG Partners Foundation; Financial Interests, Institutional, Funding: AstraZeneca; Financial Interests, Personal, Advisory Role: MSD. D.R. Spigel: Financial Interests, Institutional, Research Grant: AbbVie, Agios, Amgen, AnHeart Therapeutics, Apollomics, Arcus, Arrys Therapeutics, Ascendis Pharma, Asher Biotherapeutics, Astellas, AstraZeneca, Bayer, BeiGene, BioNTech, Blueprint Medicine, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Chugai, Cyteir Therapeutics, Daiichi Sankyo, Denovo Biopharma, Eisai, Elevation Oncology, Ellipses Pharma, EMD Serono, Endeavor, Erasca, Faeth Therapeutics, Foundation Bio, FujiFilm Pharmaceuticals, G1 Therapeutics, Roche/Genentech, Gilead Sciences, GSK, GRAIL, Hutchinson MediPharma, Incyte, Ipsen, Janssen, Janux Therapeutics, Jazz Pharmaceuticals, Kronos Bio, Lilly, Loxo Oncology, Lyell Immunopharma, MacroGenics, MedImmune, Merck, Millennium Pharmaceuticals, Moderna, Molecular Template, Monte Rosa Therapeutics, Nektar, Novartis, Novocure, Oncologie, Peloton Therapeutics, Phanes Therapeutics, PTC Therapeutics, PureTech Health, Razor Genomics, Repare Therapeutics, Rgenix, SeaGen, Shenzhen Chipscreen Biosciences, Strata Oncology, Stemline Therapeutics, Synthekine, Taiho, Takeda Pharmaceuticals, Tango Therapeutics, Tarveda, Tizona Therapeutics, Verastem, Zai Laboratory; Financial Interests, Institutional, Advisory Role: AbbVie, Amgen, AstraZeneca, Circle Pharma, Daiichi Sankyo, GSK, Jazz Pharmaceuticals, Lyell, MedImmune, ModeX Therapeutics, Novartis, Novocure, Roche/Genentech. B.C. Cho: Financial Interests, Personal, Advisory Board: KANAPH Therapeutic Inc, Bridgebio therapeutics, Cyrus therapeutics, Guardant Health, J INTS Bio, Therapex Co., Ltd; Financial Interests, Personal and Institutional, Full or part-time Employment: Yonsei University Health System; Financial Interests, Personal, Invited Speaker: ASCO, AstraZeneca, Guardant, Roche, ESMO, IASLC, Korean Cancer Association, Korean Society of Medical Oncology, Korean Society of Thyroid-Head and Neck Surgery, Korean Cancer Study Group, Novartis, MSD, The Chinese Thoracic Oncology Society, Pfizer, Zaila; Financial Interests, Institutional, Licensing Fees: Champions Oncology, Crown Bioscience, Imagen, PearlRiver Bio GmbH; Financial Interests, Personal, Member of Board of Directors: J INTS BIO; Financial Interests, Personal, Other, Founder: DAAN Biotherapeutics; Financial Interests, Institutional, Research Grant: GI Innovation, AstraZeneca, Champions Oncology, CJ bioscience, Cyrus, Janssen, MSD, Dong-A ST, Yuhan, ImmuneOncia, Therapex, JINTSbio, Vertical Bio AG; Financial Interests, Personal, Advisory Role: BeiGene, Novartis, AstraZeneca, Boehringer Ingelheim, Roche, BMS, CJ, Cyrus therapeutics, Ono, Yuhan, Pfizer, Eli Lilly, Janssen, Takeda, MSD, Gilead, Amgen, Daiichi Sankyo, Regeneron, Sanofi, AnHeart Therapeutics, Seagen, Harpoon Therapeutics, GSK, ArriV; Financial Interests, Personal, Stocks/Shares: TheraCanVac Inc, Gencurix Inc, Bridgebio therapeutics, KANAPH Therapeutic Inc, Cyrus therapeutics, Interpark Bio Convergence Corp., J INTS BIO. K. Laktionov: Financial Interests, Personal, Advisory Role: AstraZeneca/Roche/ Biocad/Pfizer/Amgen; Financial Interests, Personal, Speaker’s Bureau: AstraZeneca/Roche/ Biocad/Pfizer/Amgen/ Swixx BioPharma. Y. Zenke: Financial Interests, Personal, Advisory Board: AstraZeneca, Boehringer Ingelheim; Financial Interests, Institutional, Funding: AstraZeneca, Merck, Novocure, Daiichi Sankyo; Financial Interests, Personal, Speaker’s Bureau: AstraZeneca, Chugai pharmaceutical, Boehringer Ingelheim, Eli Lilly, MSD, Ono pharmaceutical, Novartis, Takeda pharmaceutical, Pfizer, Daiichi Sankyo pharmaceutical, Taiho pharmaceutical, Bristol Myers Squibb, Nippon Kayaku, Amgen, Kyowa Kirin, Guardant health. K.H. Lee: Other, Personal and Institutional, Funding: Merck; Financial Interests, Personal, Advisory Role: Pfizer, AstraZeneca, BMS, MSD, J&J, Eli Lilly, Boehringer Ingelheim, Daiichi Sankyo, Amgen, Takeda, Yuhan. A.F. Navarro Mendivil: Financial Interests, Personal, Advisory Board: MSD; AstraZeneca; Pfizer; Financial Interests, Personal, Advisory Role: Hengenix Biotech; MedSIR; Oryzon Genomics; Boehringer Ingelheim; Janssen; Financial Interests, Personal, Invited Speaker: Roche; Takeda; BMS; AstraZeneca; Boehringer Ingelheim; Adium; Tecnofarma; Regeneron; Eczacibasi; Financial Interests, Institutional, Principal Investigator: BMS, Roche, Celgene, PharmaMar, AstraZeneca, MSD, Amgen, Ipsen, Daiichi Sankyo, Debiopharm; Financial Interests, Personal, Other, Steering committee member: Amgen; Financial Interests, Personal, Other, Travel support to scientific meetings: Roche, Pfizer, Takeda, Janssen. I. Okamoto: Financial Interests, Personal, Funding: AstraZeneca; Non-Financial Interests, Personal, Other, Steering committee member: AstraZeneca. S. Sezgin Goksu: Financial Interests, Personal, Advisory Board: AstraZeneca, Novartis, Gilead; Financial Interests, Personal, Invited Speaker: AstraZeneca, Gilead; Financial Interests, Personal and Institutional, Principal Investigator: AstraZeneca, BMS, MSD, Lilly. A. Badzio: Financial Interests, Personal, Invited Speaker: MSD, AstraZeneca; Financial Interests, Personal, Principal Investigator: AstraZeneca. M. Zemanova: Financial Interests, Personal, Advisory Board: Roche, Astellas, MSD, AstraZeneca, BMS, Accord; Other, Personal, Other, Travel fee: MSD, AstraZeneca; Financial Interests, Personal, Invited Speaker: AstraZeneca; Financial Interests, Personal, Principal Investigator: AstraZeneca, Pfizer, Daiichi Sankyo, Iteos, Henlius, MSD, Novocure; Financial Interests, Personal, Advisory Role: Roche, Amgen, BMS, MSD, Pfizer, Pierre Fabre. N. Reinmuth: Financial Interests, Personal and Institutional, Advisory Board: Bristol Myers Squibb, AstraZeneca, Pfizer, Boehringer Ingelheim, MSD Oncology, Takeda, and Amgen; Financial Interests, Personal and Institutional, Invited Speaker: AstraZeneca, Bristol Myers Squibb, Roche, Merck Sharp & Dohme, Pfizer, Boehringer Ingelheim, Takeda, Amgen, Lilly, AbbVie, Merck KGaA, Sanofi Aventis GmbH, and Janssen Oncology; Financial Interests, Personal and Institutional, Speaker’s Bureau: AstraZeneca, Bristol Myers Squibb, Roche, Merck Sharp & Dohme, Pfizer, Boehringer Ingelheim, Takeda, Amgen, Lilly, AbbVie, Merck KGaA, Sanofi Aventis GmbH, and Janssen Oncology. P. Iyengar: Financial Interests, Personal, Advisory Board: AstraZeneca, Novocure, Pfizer, Johnson & Johnson; Financial Interests, Institutional, Research Grant: Incyte. L. Paz-Ares: Financial Interests, Personal, Research Grant: MSD, AstraZeneca, Pfizer, BMS; Financial Interests, Personal, Other, Consulting fees: Lilly, MSD, Roche, PharmaMar, Merck, AstraZeneca, Novartis, Servier, Amgen, Pfizer, Sanofi, Bayer, BMS, Mirati, GSK, Janssen, Takeda, Daiichi Sankyo; Financial Interests, Personal, Speaker’s Bureau: AstraZeneca, Janssen, Merck, Mirati. J. Chen: 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. P. Chugh: Financial Interests, Institutional, Full or part-time Employment: AstraZeneca; Financial Interests, Personal, Stocks/Shares: AstraZeneca. Y. Chen: Financial Interests, Personal, Advisory Board: AstraZeneca, Bristol Myers Squibb, AbbVie; Financial Interests, Institutional, Funding: AstraZeneca, Merck, Bristol Myers Squibb, Amgen, Daiichi Sankyo, Roche/Genentech, Junshi Shanghai, AbbVie, Eli Lilly; Financial Interests, Personal, Advisory Role: AstraZeneca, Amgen, Takeda, Jazz Pharmaceutical, Pfizer, Bristol Myers Squibb. All other authors have declared no conflicts of interest.