Efficacy and safety of first-line maintenance therapy with lurbinectedin plus atezolizumab in extensive-stage small-cell lung cancer (IMforte): a randomised, multicentre, open-label, phase 3 trial

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dc.contributor.authorPaz-Ares, Luis
dc.contributor.authorBorghaei, Hossein
dc.contributor.authorLiu, Stephen V.
dc.contributor.authorPeters, Solange
dc.contributor.authorHerbst, Roy S.
dc.contributor.authorStencel, Katarzyna
dc.contributor.authorMajem, Margarita
dc.contributor.authorŞendur, Mehmet Ali Nahit
dc.contributor.authorCzyzewicz, Grzegorz
dc.contributor.authorCaro, Reyes Bernabe
dc.contributor.authorLee, Ki Hyeong
dc.contributor.authorJohnson, Melissa L.
dc.contributor.authorKaradurmuş, Nuri
dc.contributor.authorGrohe, Christian
dc.contributor.authorBaka, Sofia
dc.contributor.authorCsoszi, Tibor
dc.contributor.authorAhn, Jin Seok
dc.contributor.authorCalifano, Raffaele
dc.contributor.authorYang, Tsung-Ying
dc.contributor.authorKemal, Yasemin
dc.contributor.authorBallinger, Marcus
dc.contributor.authorCuchelkar, Vaikunth
dc.contributor.authorGraupner, Vilma
dc.contributor.authorLin, Ya-Chen
dc.contributor.authorChakrabarti, Debasis
dc.contributor.authorBhatt, Kamalnayan
dc.contributor.authorCai, George
dc.contributor.authorIannone, Robert
dc.contributor.authorReck, Martin
dc.contributor.authorIMforte investigators
dc.date.accessioned2025-08-14T17:45:52Z
dc.date.available2025-08-14T17:45:52Z
dc.date.issued2025
dc.departmentFakülteler, Tıp Fakültesi, Dahili Tıp Bilimleri Bölümü, İç Hastalıkları Ana Bilim Dalı
dc.descriptionFunding agency : Menarini Korea ; Novartis Korea ; Pfizer ; Takeda Pharmaceutical Company Ltd ; Roche Holding ; AstraZeneca ; GlaxoSmithKline ; Merck & Company ; OSE Immunotherapeutics, PharmaMar ; BioNTech ; Bristol Myers Squibb, F Hoffmann-La Roche ; PharmaMar ; BeiGene ; European Organisation for Research and Treatment of Cancer Lung Group ; Daiichi Sankyo, F Hoffmann-La Roche ; Novartis ; Gilead Sciences ; Amgen ; BeiGene, Bristol Myers Squibb ; Boehringer Ingelheim ; Daiichi Sankyo Company Limited ; Eli Lilly ; Mirati ; Sanofi.
dc.description.abstractBackground: Despite improved efficacy with first-line immune checkpoint inhibitors plus platinum-based chemotherapy for extensive-stage small-cell lung cancer (ES-SCLC), survival remains poor. In this study, we aimed to compare lurbinectedin plus atezolizumab and atezolizumab alone as maintenance therapies in patients with ES-SCLC without progression after induction therapy with atezolizumab, carboplatin, and etoposide. Methods: IMforte was a randomised, open-label, phase 3 trial done at 96 hospitals and medical centres in 13 countries (Belgium, Germany, Greece, Hungary, Italy, Mexico, Poland, South Korea, Spain, Taiwan, Türkiye, the UK, and the USA). Eligible patients were aged 18 years or older with treatment-naive ES-SCLC. Patients received four 21-day cycles of induction treatment (atezolizumab, carboplatin, and etoposide). After completing induction treatment, eligible patients without disease progression were randomly assigned (1:1) using permuted blocks (Interactive Voice/Web Response System) to receive maintenance treatment intravenously every 3 weeks with lurbinectedin (3·2 mg/m2; with granulocyte colony-stimulating factor prophylaxis) plus atezolizumab (1200 mg) or atezolizumab (1200 mg). The two primary endpoints were independent review facility-assessed (IRF) progression-free survival and overall survival, measured from randomisation into the maintenance phase. Efficacy endpoints were assessed in the full analysis set, which included all patients who were randomly assigned to maintenance phase treatment, regardless of whether they received their assigned study treatment. Safety was assessed in all patients who received at least one dose of lurbinectedin or atezolizumab, and was analysed according to the treatment received. This study is registered with ClinicalTrials.gov, NCT05091567, and is closed for recruitment. Findings: Between Nov 17, 2021, and Jan 11, 2024, 895 patients were screened for enrolment, of whom 660 (74%) were enrolled into the induction phase. Between May 24, 2022, and April 30, 2024, 483 (73%) of 660 patients entered the maintenance phase and were randomly assigned to lurbinectedin plus atezolizumab (n=242) or atezolizumab (n=241). At the data cutoff (July 29, 2024), IRF progression-free survival was longer in the lurbinectedin plus atezolizumab group than the atezolizumab group (stratified hazard ratio [HR] 0·54 [95% CI 0·43–0·67]; p<0·0001), as was overall survival (stratified HR 0·73 [0·57–0·95]; p=0·017). 92 (38%) of 242 patients in the lurbinectedin plus atezolizumab group and 53 (22%) of 240 patients in the atezolizumab group had grade 3–4 adverse events. The most common grade 3–4 events in the lurbinectedin plus atezolizumab group were anaemia (20 [8%] of 242 patients), decreased neutrophil count (18 [7%] patients), and decreased platelet count (18 [7%] patients) and the most common events in the atezolizumab group were hyponatremia (five [2%] of 240 patients), dyspnoea (four [2%] patients), and pneumonia (four [2%] patients). Grade 5 adverse events occurred in 12 (5%) of 242 patients in the lurbinectedin plus atezolizumab group and six (3%) of 240 patients in the atezolizumab group. The incidence of myelosuppressive toxicities (eg, neutropenia and leukopenia) was higher in the lurbinectedin plus atezolizumab group than the atezolizumab group. Interpretation: IRF progression-free survival and overall survival were longer in the lurbinectedin plus atezolizumab group than the atezolizumab group for patients with ES-SCLC, albeit with a higher incidence of adverse events. Lurbinectedin plus atezolizumab represents a novel therapeutic option for first-line maintenance treatment in this setting. Funding: F Hoffmann-La Roche and Jazz Pharmaceuticals.
dc.identifier.citationPaz-Ares, L., Borghaei, H., Liu, S. V., Peters, S., Herbst, R. S., Stencel, K., ... & Reck, M. (2025). Efficacy and safety of first-line maintenance therapy with lurbinectedin plus atezolizumab in extensive-stage small-cell lung cancer (IMforte): a randomised, multicentre, open-label, phase 3 trial. The Lancet.
dc.identifier.doi10.1016/S0140-6736(25)01011-6
dc.identifier.endpage2143
dc.identifier.issn0140-6736
dc.identifier.issn1474-547X
dc.identifier.issue10495
dc.identifier.pmid40473449
dc.identifier.scopus2-s2.0-105007684682
dc.identifier.scopusqualityQ1
dc.identifier.startpage2129
dc.identifier.urihttps://hdl.handle.net/20.500.12939/5916
dc.identifier.volume405
dc.identifier.wosWOS:001513202700019
dc.identifier.wosqualityQ1
dc.indekslendigikaynakPubMed
dc.indekslendigikaynakWeb of Science
dc.indekslendigikaynakScopus
dc.institutionauthorKemal, Yasemin
dc.language.isoen
dc.publisherElsevier
dc.relation.ispartofLancet
dc.relation.publicationcategoryDiğer
dc.rightsinfo:eu-repo/semantics/closedAccess
dc.subjectAdult
dc.subjectAged
dc.subjectAntibodies
dc.subjectMonoclonal
dc.subjectHumanized
dc.subjectAntineoplastic Combined Chemotherapy Protocols
dc.subjectCarbolines
dc.subjectCarboplatin
dc.subjectEtoposide
dc.subjectFemale
dc.subjectHeterocyclic Compounds
dc.subject4 or More Rings
dc.subjectHumans
dc.subjectLung Neoplasms
dc.subjectMaintenance Chemotherapy
dc.subjectMale
dc.subjectMiddle Aged
dc.subjectProgression-Free Survival
dc.subjectSmall Cell Lung Carcinoma
dc.subjectTreatment Outcome
dc.subjectatezolizumab
dc.subjectcarboplatin
dc.subjectetoposide
dc.subjectgranulocyte colony stimulating factor
dc.subjectlurbinectedin
dc.subjectantineoplastic agent
dc.subjectcarboline derivative
dc.subjectfused heterocyclic rings
dc.subjectmonoclonal antibody
dc.subjectaged
dc.subjectanemia
dc.subjectArticle
dc.subjectcancer survival
dc.subjectclinical outcome
dc.subjectcontrolled study
dc.subjectdisease exacerbation
dc.subjectdrug efficacy
dc.subjectdrug safety
dc.subjectdyspnea
dc.subjectECOG Performance Status
dc.subjectextensive stage small cell lung cancer
dc.subjectfemale
dc.subjecthuman
dc.subjecthyponatremia
dc.subjectlung cancer
dc.subjectlymphocytopenia
dc.subjectmaintenance therapy
dc.subjectmajor clinical study
dc.subjectmale
dc.subjectmulticenter study
dc.subjectneutropenia
dc.subjectoverall response rate
dc.subjectoverall survival
dc.subjectphase 3 clinical trial
dc.subjectpneumonia
dc.subjectprogression free survival
dc.subjectrandomized controlled trial
dc.subjectthrombocytopenia
dc.subjecttreatment response
dc.subjectadult
dc.subjectclinical trial
dc.subjectdrug therapy
dc.subjectlung tumor
dc.subjectmaintenance chemotherapy
dc.subjectmiddle aged
dc.subjectmortality
dc.subjectpathology
dc.subjectprocedures
dc.subjectsmall cell lung cancer
dc.subjecttreatment outcome
dc.titleEfficacy and safety of first-line maintenance therapy with lurbinectedin plus atezolizumab in extensive-stage small-cell lung cancer (IMforte): a randomised, multicentre, open-label, phase 3 trial
dc.typeOther

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