TY - BOOK AU - Swain, Sandra M TI - 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 SN - 0923-7534 PY - 2024/// KW - *Antibodies, Monoclonal, Humanized KW - *Antineoplastic Combined Chemotherapy Protocols KW - *Gemcitabine KW - *Neoplasm Recurrence, Local KW - *Triple Negative Breast Neoplasms KW - Adult KW - Aged KW - Antibodies, Monoclonal, Humanized/ad [Administration & Dosage] KW - Antibodies, Monoclonal, Humanized/ae [Adverse Effects] KW - Antineoplastic Combined Chemotherapy Protocols/ae [Adverse Effects] KW - Antineoplastic Combined Chemotherapy Protocols/tu [Therapeutic Use] KW - B7-H1 Antigen/ai [Antagonists & Inhibitors] KW - B7-H1 Antigen/me [Metabolism] KW - Capecitabine/ad [Administration & Dosage] KW - Carboplatin/ad [Administration & Dosage] KW - Deoxycytidine/aa [Analogs & Derivatives] KW - Deoxycytidine/ad [Administration & Dosage] KW - Deoxycytidine/tu [Therapeutic Use] KW - Double-Blind Method KW - Female KW - Humans KW - Immune Checkpoint Inhibitors/ad [Administration & Dosage] KW - Immune Checkpoint Inhibitors/ae [Adverse Effects] KW - Middle Aged KW - Neoplasm Recurrence, Local/dt [Drug Therapy] KW - Neoplasm Recurrence, Local/pa [Pathology] KW - Progression-Free Survival KW - Triple Negative Breast Neoplasms/dt [Drug Therapy] KW - Triple Negative Breast Neoplasms/pa [Pathology] KW - Automated KW - Associate Dean for Research Development KW - Clinical Trial, Phase III KW - Journal Article KW - Multicenter Study KW - Randomized Controlled Trial N1 - Available online from MWHC library: 1996 - present, Available in print through MWHC library: 1999 - 2006 N2 - 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; 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. Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved; 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 UR - https://dx.doi.org/10.1016/j.annonc.2024.04.001 ER -