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

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; Schroder, CP; Linn, SC; Kok, M

Author(s): 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; Schroder, CP; Linn, SC; Kok, M;
Details: Publication Year 2023-04,Volume 4,Issue #4,Page 535-549
Journal Title: Nature Cancer
Publication Type: Research article
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.
Publisher: Springer Nature
Keywords: Animals; Humans; Mice; B7-H1 Antigen; Carboplatin/therapeutic use; *Carcinoma, Lobular/drug therapy/pathology; *Triple Negative Breast Neoplasms/drug therapy/pathology
Department(s): Laboratory Research
PubMed ID: 37038006
Publisher's Version: https://doi.org/10.1038/s43018-023-00542-x
Open Access at Publisher's Site: https://doi.org/10.1038/s43018-023-00542-x
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2023-08-07 07:16:22

Last Modified: 2023-08-07 07:17:40