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PD-L1 blockade in combination with carboplatin as immune induction in metastatic lobular breast cancer: the GELATO trial.

Authors :
Voorwerk L
Isaeva OI
Horlings HM
Balduzzi S
Chelushkin M
Bakker NAM
Champanhet E
Garner H
Sikorska K
Loo CE
Kemper I
Mandjes IAM
de Maaker M
van Geel JJL
Boers J
de Boer M
Salgado R
van Dongen MGJ
Sonke GS
de Visser KE
Schumacher TN
Blank CU
Wessels LFA
Jager A
Tjan-Heijnen VCG
Schröder CP
Linn SC
Kok M
Source :
Nature cancer [Nat Cancer] 2023 Apr; Vol. 4 (4), pp. 535-549. Date of Electronic Publication: 2023 Apr 10.
Publication Year :
2023

Abstract

Invasive lobular breast cancer (ILC) is the second most common histological breast cancer subtype, but ILC-specific trials are lacking. Translational research revealed an immune-related ILC subset, and in mouse ILC models, synergy between immune checkpoint blockade and platinum was observed. In the phase II GELATO trial ( NCT03147040 ), patients with metastatic ILC were treated with weekly carboplatin (area under the curve 1.5 mg ml <superscript>-1</superscript> min <superscript>-1</superscript> ) as immune induction for 12 weeks and atezolizumab (PD-L1 blockade; triweekly) from the third week until progression. Four of 23 evaluable patients had a partial response (17%), and 2 had stable disease, resulting in a clinical benefit rate of 26%. From these six patients, four had triple-negative ILC (TN-ILC). We observed higher CD8 <superscript>+</superscript> T cell infiltration, immune checkpoint expression and exhausted T cells after treatment. With this GELATO trial, we show that ILC-specific clinical trials are feasible and demonstrate promising antitumor activity of atezolizumab with carboplatin, particularly for TN-ILC, and provide insights for the design of highly needed ILC-specific trials.<br /> (© 2023. The Author(s).)

Details

Language :
English
ISSN :
2662-1347
Volume :
4
Issue :
4
Database :
MEDLINE
Journal :
Nature cancer
Publication Type :
Academic Journal
Accession number :
37038006
Full Text :
https://doi.org/10.1038/s43018-023-00542-x