dc.contributor.author | Dent, R. | |
dc.contributor.author | André, F. | |
dc.contributor.author | Gonçalves, A. | |
dc.contributor.author | Martin, M. | |
dc.contributor.author | Schmid, P. | |
dc.contributor.author | Schütz, F. | |
dc.contributor.author | Kümmel, S. | |
dc.contributor.author | Swain, S.M. | |
dc.contributor.author | Bilici, Ahmet | |
dc.contributor.author | Loirat, D. | |
dc.contributor.author | Villalobos, Valencia R. | |
dc.contributor.author | Im, S. A. | |
dc.contributor.author | Park, Y. H. | |
dc.contributor.author | De Laurentis, M. | |
dc.contributor.author | Colleoni, M. | |
dc.contributor.author | Guarneri, V. | |
dc.contributor.author | Bianchini, G. | |
dc.contributor.author | Li, H. | |
dc.contributor.author | Kirchmayer Machackova, Z. | |
dc.contributor.author | Mouta, J. | |
dc.contributor.author | Deurloo, R. | |
dc.contributor.author | Gan, X. | |
dc.contributor.author | Fan, M. | |
dc.contributor.author | Mani, A. | |
dc.contributor.author | Swat, A. | |
dc.contributor.author | Cortés, J. | |
dc.date.accessioned | 2024-07-02T10:48:33Z | |
dc.date.available | 2024-07-02T10:48:33Z | |
dc.date.issued | 2024 | en_US |
dc.identifier.citation | Dent, 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 | en_US |
dc.identifier.issn | 0923-7534 | |
dc.identifier.uri | http://dx.doi.org/10.1016/j.annonc.2024.04.001 | |
dc.identifier.uri | https://hdl.handle.net/20.500.12511/12688 | |
dc.description.abstract | Background: 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. | en_US |
dc.language.iso | eng | en_US |
dc.rights | info:eu-repo/semantics/openAccess | en_US |
dc.rights | Attribution-NonCommercial-NoDerivatives 4.0 International | * |
dc.rights.uri | https://creativecommons.org/licenses/by-nc-nd/4.0/ | * |
dc.subject | Disease-Free Interval | en_US |
dc.subject | Immune Checkpoint | en_US |
dc.subject | PD-L1 | en_US |
dc.subject | Prognosis | en_US |
dc.subject | Rapid Relapse | en_US |
dc.subject | Triple-Negative Breast Cancer | en_US |
dc.title | 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 | en_US |
dc.type | article | en_US |
dc.relation.ispartof | Annals of Oncology | en_US |
dc.department | İstanbul Medipol Üniversitesi, Tıp Fakültesi, Tıbbi Onkoloji Anabilim Dalı | en_US |
dc.department | İstanbul Medipol Üniversitesi, Tıp Fakültesi, Dahili Tıp Bilimleri Bölümü, İç Hastalıkları Ana Bilim Dalı | en_US |
dc.identifier.volume | 35 | en_US |
dc.identifier.issue | 7 | en_US |
dc.identifier.startpage | 630 | en_US |
dc.identifier.endpage | 642 | en_US |
dc.relation.publicationcategory | Makale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanı | en_US |
dc.identifier.doi | 10.1016/j.annonc.2024.04.001 | en_US |
dc.institutionauthor | Bilici, Ahmet | |
dc.identifier.scopus | 2-s2.0-85194586344 | en_US |
dc.identifier.pmid | 38755096 | en_US |
dc.identifier.scopusquality | Q1 | en_US |