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
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...
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| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
July 2024
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| In: |
Annals of oncology
Year: 2024, Volume: 35, Issue: 7, Pages: 630-642 |
| ISSN: | 1569-8041 |
| DOI: | 10.1016/j.annonc.2024.04.001 |
| Online Access: | Verlag, kostenfrei, Volltext: https://doi.org/10.1016/j.annonc.2024.04.001 Verlag, kostenfrei, Volltext: https://www.sciencedirect.com/science/article/pii/S0923753424001078 
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| Author Notes: | R. Dent, F. André, A. Gonçalves, M. Martin, P. Schmid, F. Schütz, S. Kümmel, S.M. Swain, A. Bilici, D. Loirat, R. Villalobos Valencia, S.-A. Im, Y.H. Park, M. De Laurentis, M. Colleoni, V. Guarneri, G. Bianchini, H. Li, Z. Kirchmayer Machackova, J. Mouta, R. Deurloo, X. Gan, M. Fan, A. Mani, A. Swat & J. Cortés |
| Summary: | 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. |
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| Item Description: | Online verfügbar: 15. Mai 2024, Artikelversion: 21. Juni 2024 Gesehen am 12.11.2024 |
| Physical Description: | Online Resource |
| ISSN: | 1569-8041 |
| DOI: | 10.1016/j.annonc.2024.04.001 |