IMpassion132 double-blind randomised phase III trial of chemotherapy with or without atezolizumab for early relapsing unresectable locally advanced or metastatic triple-negative breast cancer

Basit Öğe Kaydı
dc.contributor.authorDent, R.
dc.contributor.authorAndré, F.
dc.contributor.authorGonçalves, A.
dc.contributor.authorMartin, M.
dc.contributor.authorSchmid, P.
dc.contributor.authorSchütz, F.
dc.contributor.authorKümmel, S.
dc.contributor.authorSwain, S.M.
dc.contributor.authorBilici, Ahmet
dc.contributor.authorLoirat, D.
dc.contributor.authorVillalobos, Valencia R.
dc.contributor.authorIm, S. A.
dc.contributor.authorPark, Y. H.
dc.contributor.authorDe Laurentis, M.
dc.contributor.authorColleoni, M.
dc.contributor.authorGuarneri, V.
dc.contributor.authorBianchini, G.
dc.contributor.authorLi, H.
dc.contributor.authorKirchmayer Machackova, Z.
dc.contributor.authorMouta, J.
dc.contributor.authorDeurloo, R.
dc.contributor.authorGan, X.
dc.contributor.authorFan, M.
dc.contributor.authorMani, A.
dc.contributor.authorSwat, A.
dc.contributor.authorCortés, J.
dc.date.accessioned2024-07-02T10:48:33Z
dc.date.available2024-07-02T10:48:33Z
dc.date.issued2024
dc.departmentİstanbul Medipol Üniversitesi, Tıp Fakültesi, Tıbbi Onkoloji Anabilim Dalı
dc.departmentİstanbul Medipol Üniversitesi, Tıp Fakültesi, Dahili Tıp Bilimleri Bölümü, İç Hastalıkları Ana Bilim Dalı
dc.description.abstractBackground: Immune checkpoint inhibitors improve the efficacy of first-line chemotherapy for patients with programmed death-ligand 1 (PD-L1)-positive unresectable locally advanced/metastatic triple-negative breast cancer (aTNBC), but randomised data in rapidly relapsing aTNBC are scarce. Patients and methods: IMpassion132 (NCT03371017) enrolled patients with aTNBC relapsing <12 months after last chemotherapy dose (anthracycline and taxane required) or surgery for early TNBC. PD-L1 status was centrally assessed using SP142 before randomisation. Initially patients were enrolled irrespective of PD-L1 status. From August 2019, enrolment was restricted to PD-L1-positive (tumour immune cell ?1%) aTNBC. Patients were randomised 1:1 to placebo or atezolizumab 1200 mg every 21 days with investigator-selected chemotherapy until disease progression or unacceptable toxicity. Stratification factors were chemotherapy regimen (carboplatin plus gemcitabine or capecitabine monotherapy), visceral (lung and/or liver) metastases and (initially) PD-L1 status. The primary endpoint was overall survival (OS), tested hierarchically in patients with PD-L1-positive tumours and then, if positive, in the modified intent-to-treat (mITT) population (all-comer patients randomised pre-August 2019). Secondary endpoints included progression-free survival (PFS), objective response rate (ORR) and safety. Results: Among 354 patients with rapidly relapsing PD-L1-positive aTNBC, 68% had a disease-free interval of <6 months and 73% received carboplatin/gemcitabine. The OS hazard ratio was 0.93 (95% confidence interval 0.73-1.20, P = 0.59; median 11.2 months with placebo versus 12.1 months with atezolizumab). mITT and subgroup results were consistent. Median PFS was 4 months across treatment arms and populations. ORRs were 28% with placebo versus 40% with atezolizumab. Adverse events (predominantly haematological) were similar between arms and as expected with atezolizumab plus carboplatin/gemcitabine or capecitabine following recent chemotherapy exposure. Conclusions: OS, which is dismal in patients with TNBC relapsing within <12 months, was not improved by adding atezolizumab to chemotherapy. A biology-based definition of intrinsic resistance to immunotherapy in aTNBC is urgently needed to develop novel therapies for these patients in next-generation clinical trials.
dc.description.sponsorshipRoche Holding
dc.identifier.citationDent, R., André, F., Gonçalves, A., Martin, M., Schmid, P., Schütz, F. ... Cortés, J. (2024). IMpassion132 double-blind randomised phase III trial of chemotherapy with or without atezolizumab for early relapsing unresectable locally advanced or metastatic triple-negative breast cancer. Annals of Oncology, 35(7), 630-642. http://dx.doi.org/10.1016/j.annonc.2024.04.001
dc.identifier.doi10.1016/j.annonc.2024.04.001
dc.identifier.endpage642
dc.identifier.issn0923-7534
dc.identifier.issn1569-8041
dc.identifier.issue7
dc.identifier.pmid38755096
dc.identifier.scopus2-s2.0-85194586344
dc.identifier.scopusqualityQ1
dc.identifier.startpage630
dc.identifier.urihttp://dx.doi.org/10.1016/j.annonc.2024.04.001
dc.identifier.urihttps://hdl.handle.net/20.500.12511/12688
dc.identifier.volume35
dc.identifier.wosWOS:001296652200001
dc.identifier.wosqualityQ1
dc.indekslendigikaynakScopus
dc.indekslendigikaynakPubMed
dc.institutionauthorBilici, Ahmet
dc.language.isoen
dc.relation.ispartofAnnals of Oncologyen_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanı
dc.rightsAttribution-NonCommercial-NoDerivatives 4.0 International*
dc.rightsinfo:eu-repo/semantics/openAccess
dc.rights.urihttps://creativecommons.org/licenses/by-nc-nd/4.0/*
dc.subjectDisease-Free Interval
dc.subjectImmune Checkpoint
dc.subjectPD-L1
dc.subjectPrognosis
dc.subjectRapid Relapse
dc.subjectTriple-Negative Breast Cancer
dc.titleIMpassion132 double-blind randomised phase III trial of chemotherapy with or without atezolizumab for early relapsing unresectable locally advanced or metastatic triple-negative breast cancer
dc.typeArticle

Dosyalar

Orijinal paket
Listeleniyor 1 - 1 / 1
Küçük Resim
İsim:
Bilici-Ahmet-2024.pdf
Boyut:
1000.3 KB
Biçim:
Adobe Portable Document Format
Açıklama:
Tam Metin / Full Text
İndir
Lisans paketi
Listeleniyor 1 - 1 / 1
Küçük Resim Yok
İsim:
license.txt
Boyut:
1.44 KB
Biçim:
Item-specific license agreed upon to submission
Açıklama:
İndir

Koleksiyon

Makale Koleksiyonu
Makale Koleksiyonu
PubMed İndeksli Yayınlar Koleksiyonu
Scopus İndeksli Yayınlar Koleksiyonu
WoS İndeksli Yayınlar Koleksiyonu