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 Visser; Ton N Schumacher; Christian U Blank; Lodewyk F A Wessels; Agnes Jager; Vivianne C G Tjan-Heijnen; Carolien P Schröder; Sabine C Linn; Marleen Kok

doi:10.1038/s43018-023-00542-x

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 journal › Article › Academic › peer-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 language	English
Pages (from-to)	535-549
Number of pages	15
Journal	Nature Cancer
Volume	4
DOIs	https://doi.org/10.1038/s43018-023-00542-x
Publication status	Published - Apr-2023

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PD-L1 blockade in combination with carboplatin as immune induction in metastatic lobular breast cancerFinal publisher's version, 6.77 MBLicence: CC BY

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Voorwerk, L., Isaeva, O. I., Horlings, H. M., Balduzzi, S., Chelushkin, M., Bakker, N. A. M., Champanhet, E., Garner, H., Sikorska, K., Loo, C. E., Kemper, I., Mandjes, I. A. M., de Maaker, M., van Geel, J. J. L., Boers, J., de Boer, M., Salgado, R., van Dongen, M. G. J., Sonke, G. S., ... Kok, M. (2023). PD-L1 blockade in combination with carboplatin as immune induction in metastatic lobular breast cancer: the GELATO trial. Nature Cancer, 4, 535-549. https://doi.org/10.1038/s43018-023-00542-x

@article{01a4579e0b1a474691a251bc622d82d2,

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

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. ",

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

note = "{\textcopyright} 2023. The Author(s).",

year = "2023",

month = apr,

doi = "10.1038/s43018-023-00542-x",

language = "English",

volume = "4",

pages = "535--549",

journal = "Nature Cancer",

issn = "2662-1347",

publisher = "Springer Nature",

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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 2023, 'PD-L1 blockade in combination with carboplatin as immune induction in metastatic lobular breast cancer: the GELATO trial', Nature Cancer, vol. 4, pp. 535-549. https://doi.org/10.1038/s43018-023-00542-x

TY - JOUR

T1 - PD-L1 blockade in combination with carboplatin as immune induction in metastatic lobular breast cancer

T2 - the GELATO trial

AU - Voorwerk, Leonie

AU - Isaeva, Olga I

AU - Horlings, Hugo M

AU - Balduzzi, Sara

AU - Chelushkin, Maksim

AU - Bakker, Noor A M

AU - Champanhet, Elisa

AU - Garner, Hannah

AU - Sikorska, Karolina

AU - Loo, Claudette E

AU - Kemper, Inge

AU - Mandjes, Ingrid A M

AU - de Maaker, Michiel

AU - van Geel, Jasper J L

AU - Boers, Jorianne

AU - de Boer, Maaike

AU - Salgado, Roberto

AU - van Dongen, Marloes G J

AU - Sonke, Gabe S

AU - de Visser, Karin E

AU - Schumacher, Ton N

AU - Blank, Christian U

AU - Wessels, Lodewyk F A

AU - Jager, Agnes

AU - Tjan-Heijnen, Vivianne C G

AU - Schröder, Carolien P

AU - Linn, Sabine C

AU - Kok, Marleen

PY - 2023/4

Y1 - 2023/4

N2 - 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.

AB - 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.

U2 - 10.1038/s43018-023-00542-x

DO - 10.1038/s43018-023-00542-x

M3 - Article

C2 - 37038006

SN - 2662-1347

VL - 4

SP - 535

EP - 549

JO - Nature Cancer

JF - Nature Cancer

ER -

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

Abstract

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