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

Leonie Voorwerk, Olga I Isaeva, Hugo M Horlings, Sara Balduzzi, Maksim Chelushkin, Noor A M Bakker, Elisa Champanhet, Hannah Garner, Karolina Sikorska, Claudette E Loo, Inge Kemper, Ingrid A M Mandjes, Michiel de Maaker, Jasper J L van Geel, Jorianne Boers, Maaike de Boer, Roberto Salgado, Marloes G J van Dongen, Gabe S Sonke, Karin E de VisserTon N Schumacher, Christian U Blank, Lodewyk F A Wessels, Agnes Jager, Vivianne C G Tjan-Heijnen, Carolien P Schröder, Sabine C Linn, Marleen Kok*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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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 -1 min -1) 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 + 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.

Original languageEnglish
Pages (from-to)535-549
Number of pages15
JournalNature Cancer
Volume4
DOIs
Publication statusPublished - Apr-2023

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