{"entity":{"id":"paper-cheng-adriatic-durvalumab-limited-stage-sclc-nejm-2024","kind":"paper","name":"Durvalumab after chemoradiotherapy in limited-stage small-cell lung cancer","aka":[],"tldr":"ADRIATIC gave immunotherapy after chemoradiotherapy for limited-stage small-cell lung cancer and lifted median survival from 33.4 to 55.9 months, the largest gain the disease has seen.","summary":"The ADRIATIC investigators, reported by Cheng, Spigel, Cho and colleagues with Senan as senior author, randomised patients with limited-stage small-cell lung cancer who had not progressed after concurrent platinum-based chemoradiotherapy to durvalumab 1500 mg (264), durvalumab with tremelimumab 75 mg (200) or placebo (266), every four weeks for up to 24 months. Randomisation was stratified by disease stage and receipt of prophylactic cranial irradiation, and the durvalumab-tremelimumab group remained blinded at this report.\n\nIt is the PACIFIC design transplanted into small-cell disease, and it worked better. A 22-month gain in median overall survival is without precedent in this cancer.","asOf":"2026-09-25","links":[{"label":"N Engl J Med 2024","url":"https://doi.org/10.1056/NEJMoa2404873"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/39268857/"},{"label":"ClinicalTrials.gov NCT03703297","url":"https://clinicaltrials.gov/study/NCT03703297"}],"tags":["lung-evidence"],"related":["paper-turrisi-twice-daily-thoracic-radiotherapy-limited-sclc-nejm-1999","paper-spigel-pacific-five-year-survival-jco-2022","paper-paz-ares-caspian-durvalumab-es-sclc-lancet-2019"],"cancers":["lung-cancer","sclc","limited-stage-sclc"],"sections":["immunotherapy","radiation"],"technologies":["radiotherapy","checkpoint-inhibitor"],"targets":["pd1"],"drugs":["durvalumab","tremelimumab"],"companies":["astrazeneca"],"institutions":[],"pathways":["immune-checkpoint"],"terms":["chemoradiation","prophylactic-cranial-irradiation"],"trials":["adriatic"],"people":[],"bottlenecks":["b-immunotherapy-response","b-rare-cancers","b-biomarker-validation"],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2024,"doi":"10.1056/NEJMoa2404873","pmid":"39268857","authors":"Cheng Y, Spigel DR, Cho BC, et al.","paperType":"rct","findings":["Median overall survival 55.9 months (95 percent confidence interval 37.3 to not reached) with durvalumab against 33.4 months (25.5 to 39.9) with placebo: hazard ratio for death 0.73 (98.321 percent confidence interval 0.54 to 0.98; P equals 0.01).","Median progression-free survival 16.6 months (10.2 to 28.2) against 9.2 months (7.4 to 12.9): hazard ratio 0.76 (97.195 percent confidence interval 0.59 to 0.98; P equals 0.02).","Maximum grade 3 or 4 adverse events in 24.4 percent on durvalumab and 24.2 percent on placebo.","Adverse events led to discontinuation in 16.4 percent and 10.6 percent, and to death in 2.7 percent and 1.9 percent.","Grade 3 or 4 pneumonitis or radiation pneumonitis in 3.1 percent on durvalumab and 2.6 percent on placebo."],"whatItMeans":"The biggest single advance in small-cell lung cancer since twice-daily radiotherapy in 1999, and the strongest argument that the disease responds to immunotherapy when it is given at a lower tumour burden.","caveats":["Only patients who completed chemoradiotherapy without progressing were randomised, so the population is selected.","The durvalumab plus tremelimumab arm was still blinded, so the contribution of CTLA-4 blockade is unknown.","No biomarker selects who benefits, and 24 months of treatment is given to everybody, including those already cured."],"changedPractice":true,"participants":730},"route":"/key-papers/paper-cheng-adriatic-durvalumab-limited-stage-sclc-nejm-2024/","neighbours":{"paper":[{"id":"paper-paz-ares-caspian-durvalumab-es-sclc-lancet-2019","kind":"paper","name":"Durvalumab plus platinum-etoposide versus platinum-etoposide in first-line treatment of extensive-stage small-cell lung cancer (CASPIAN)","route":"/key-papers/paper-paz-ares-caspian-durvalumab-es-sclc-lancet-2019/"},{"id":"paper-spigel-pacific-five-year-survival-jco-2022","kind":"paper","name":"Five-year survival outcomes from the PACIFIC trial: durvalumab after chemoradiotherapy in stage III non-small-cell lung cancer","route":"/key-papers/paper-spigel-pacific-five-year-survival-jco-2022/"},{"id":"paper-turrisi-twice-daily-thoracic-radiotherapy-limited-sclc-nejm-1999","kind":"paper","name":"Twice-daily compared with once-daily thoracic radiotherapy in limited small-cell lung cancer treated concurrently with cisplatin and etoposide","route":"/key-papers/paper-turrisi-twice-daily-thoracic-radiotherapy-limited-sclc-nejm-1999/"}],"cancer":[{"id":"limited-stage-sclc","kind":"cancer","name":"Limited-stage small-cell lung cancer","route":"/cancers/limited-stage-sclc/"},{"id":"lung-cancer","kind":"cancer","name":"Lung cancer (all types)","route":"/cancers/lung-cancer/"},{"id":"sclc","kind":"cancer","name":"Small-cell lung cancer","route":"/cancers/sclc/"}],"section":[{"id":"immunotherapy","kind":"section","name":"Immunotherapy","route":"/fronts/immunotherapy/"},{"id":"radiation","kind":"section","name":"Radiation Therapy","route":"/fronts/radiation/"}],"term":[{"id":"chemoradiation","kind":"term","name":"Chemoradiation (chemoradiotherapy, CRT)","route":"/terms/chemoradiation/"},{"id":"immune-checkpoint","kind":"term","name":"Immune checkpoint","route":"/terms/immune-checkpoint/"},{"id":"radiotherapy","kind":"term","name":"Radiotherapy","route":"/terms/radiotherapy/"}],"technology":[{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"},{"id":"prophylactic-cranial-irradiation","kind":"technology","name":"Prophylactic cranial irradiation vs MRI surveillance","route":"/technologies/prophylactic-cranial-irradiation/"}],"target":[{"id":"pd1","kind":"target","name":"PD-1","route":"/targets/pd1/"}],"drug":[{"id":"durvalumab","kind":"drug","name":"Durvalumab","route":"/drugs/durvalumab/"},{"id":"tremelimumab","kind":"drug","name":"Tremelimumab","route":"/drugs/tremelimumab/"}],"company":[{"id":"astrazeneca","kind":"company","name":"AstraZeneca","route":"/companies/astrazeneca/"}],"trial":[{"id":"adriatic","kind":"trial","name":"ADRIATIC","route":"/trials/adriatic/"}],"bottleneck":[{"id":"b-biomarker-validation","kind":"bottleneck","name":"Biomarkers are not validated or standardised","route":"/bottlenecks/b-biomarker-validation/"},{"id":"b-immunotherapy-response","kind":"bottleneck","name":"No one can predict who responds to immunotherapy","route":"/bottlenecks/b-immunotherapy-response/"},{"id":"b-rare-cancers","kind":"bottleneck","name":"Rare and paediatric cancers without markets","route":"/bottlenecks/b-rare-cancers/"}],"journal":[{"id":"nejm","kind":"journal","name":"New England Journal of Medicine","route":"/journals/nejm/"}],"roadmap":[{"id":"lung-cancer-evidence-roadmap","kind":"roadmap","name":"Lung cancer roadmap: from Doll and Hill and the naming of tobacco, through the cytotoxic plateau, computed tomography screening, EGFR and ALK, immunotherapy by PD-L1, the perioperative trials and PACIFIC, to DLL3 in small-cell disease and a 2032 registry watch","route":"/roadmaps/lung-cancer-evidence-roadmap/"}]}}