000			05764nam a22007697a 4500
008			240807s20242024 xxu||||| |||| 00| 0 eng d
022			_a0923-7534
024			_aS0923-7534(24)00107-8 [pii]
040			_aOvid MEDLINE(R)
099			_a38755096
245			_aIMpassion132 double-blind randomised phase III trial of chemotherapy with or without atezolizumab for early relapsing unresectable locally advanced or metastatic triple-negative breast cancer.
251			_aAnnals of Oncology. 35(7):630-642, 2024 Jul.
252			_aAnn Oncol. 35(7):630-642, 2024 Jul.
253			_aAnnals of oncology : official journal of the European Society for Medical Oncology
260			_c2024
260			_fFY2024
260			_p2024 Jul
265			_sppublish
265			_tMEDLINE
266			_d2024-08-07
266			_z2024/05/16 22:00
501			_aAvailable online from MWHC library: 1996 - present, Available in print through MWHC library: 1999 - 2006
520			_aBACKGROUND: 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.
520			_aCONCLUSIONS: 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. Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.
520			_aPATIENTS 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.
520			_aRESULTS: 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.
546			_aEnglish
650			_a*Antibodies, Monoclonal, Humanized
650			_a*Antineoplastic Combined Chemotherapy Protocols
650			_a*Gemcitabine
650			_a*Neoplasm Recurrence, Local
650			_a*Triple Negative Breast Neoplasms
650			_aAdult
650			_aAged
650			_aAntibodies, Monoclonal, Humanized/ad [Administration & Dosage]
650			_aAntibodies, Monoclonal, Humanized/ae [Adverse Effects]
650			_aAntineoplastic Combined Chemotherapy Protocols/ae [Adverse Effects]
650			_aAntineoplastic Combined Chemotherapy Protocols/tu [Therapeutic Use]
650			_aB7-H1 Antigen/ai [Antagonists & Inhibitors]
650			_aB7-H1 Antigen/me [Metabolism]
650			_aCapecitabine/ad [Administration & Dosage]
650			_aCarboplatin/ad [Administration & Dosage]
650			_aDeoxycytidine/aa [Analogs & Derivatives]
650			_aDeoxycytidine/ad [Administration & Dosage]
650			_aDeoxycytidine/tu [Therapeutic Use]
650			_aDouble-Blind Method
650			_aFemale
650			_aHumans
650			_aImmune Checkpoint Inhibitors/ad [Administration & Dosage]
650			_aImmune Checkpoint Inhibitors/ae [Adverse Effects]
650			_aMiddle Aged
650			_aNeoplasm Recurrence, Local/dt [Drug Therapy]
650			_aNeoplasm Recurrence, Local/pa [Pathology]
650			_aProgression-Free Survival
650			_aTriple Negative Breast Neoplasms/dt [Drug Therapy]
650			_aTriple Negative Breast Neoplasms/pa [Pathology]
650			_zAutomated
656			_aAssociate Dean for Research Development
657			_aClinical Trial, Phase III
657			_aJournal Article
657			_aMulticenter Study
657			_aRandomized Controlled Trial
700			_aSwain, Sandra M _bMSH =656 \\ _aMedStar Health
790			_aDent R, Andre F, Goncalves A, Martin M, Schmid P, Schutz F, Kummel S, Swain SM, Bilici A, Loirat D, Villalobos Valencia R, Im SA, Park YH, De Laurentis M, Colleoni M, Guarneri V, Bianchini G, Li H, Kirchmayer Machackova Z, Mouta J, Deurloo R, Gan X, Fan M, Mani A, Swat A, Cortes J
856			_uhttps://dx.doi.org/10.1016/j.annonc.2024.04.001 _zhttps://dx.doi.org/10.1016/j.annonc.2024.04.001
942			_cART _dArticle
999			_c14577 _d14577