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

Leonie Voorwerk; Olga I. I. Isaeva; Hugo M. M. Horlings; Sara Balduzzi; Maksim Chelushkin; Noor A. M. Bakker; Elisa Champanhet; Hannah Garner; Karolina Sikorska; Claudette E. 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. S. Sonke; Karin E. E. de Visser; Ton N. N. Schumacher; Christian U. U. Blank; Lodewyk F. A. Wessels; Agnes Jager; Vivianne C. G. Tjan-Heijnen; Carolien P. Schroder; Sabine C. 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. I. Isaeva, Hugo M. M. Horlings, Sara Balduzzi, Maksim Chelushkin, Noor A. M. Bakker, Elisa Champanhet, Hannah Garner, Karolina Sikorska, Claudette E. 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. S. Sonke, Karin E. E. de VisserTon N. N. Schumacher, Christian U. U. Blank, Lodewyk F. A. Wessels, Agnes Jager, Vivianne C. G. Tjan-Heijnen, Carolien P. Schroder, Sabine C. C. Linn, Marleen Kok^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

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 (), 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	28
Journal	Nature Cancer
Volume	4
Issue number	4
DOIs	https://doi.org/10.1038/s43018-023-00542-x
Publication status	Published - 1 Apr 2023

Keywords

LOCALLY RECURRENT
CARCINOMA
EXPRESSION
IMMUNOTHERAPY
CHEMOTHERAPY
MULTICENTER
SIGNATURES
SURVIVAL
FEATURES
CRITERIA

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Cite this

Voorwerk, L., Isaeva, O. I. I., Horlings, H. M. M., Balduzzi, S., Chelushkin, M., Bakker, N. A. M., Champanhet, E., Garner, H., Sikorska, K., Loo, C. E. 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. 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(4), 535–549. https://doi.org/10.1038/s43018-023-00542-x

@article{7980364ba2f546a1b5502bf6e650af85,

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 (), 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.",

keywords = "LOCALLY RECURRENT, CARCINOMA, EXPRESSION, IMMUNOTHERAPY, CHEMOTHERAPY, MULTICENTER, SIGNATURES, SURVIVAL, FEATURES, CRITERIA",

author = "Leonie Voorwerk and Isaeva, {Olga I. I.} and Horlings, {Hugo M. 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. 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. S.} and {de Visser}, {Karin E. E.} and Schumacher, {Ton N. N.} and Blank, {Christian U. U.} and Wessels, {Lodewyk F. A.} and Agnes Jager and Tjan-Heijnen, {Vivianne C. G.} and Schroder, {Carolien P.} and Linn, {Sabine C. C.} and Marleen Kok",

year = "2023",

month = apr,

day = "1",

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

language = "English",

volume = "4",

pages = "535–549",

journal = "Nature Cancer",

issn = "2662-1347",

publisher = "Nature Publishing Group",

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}

Voorwerk, L, Isaeva, OII, Horlings, HMM, Balduzzi, S, Chelushkin, M, Bakker, NAM, Champanhet, E, Garner, H, Sikorska, K, Loo, CEE, Kemper, I, Mandjes, IAM, de Maaker, M, van Geel, JJL, Boers, J, de Boer, M, Salgado, R, van Dongen, MGJ, Sonke, GSS, de Visser, KEE, Schumacher, TNN, Blank, CUU, Wessels, LFA, Jager, A, Tjan-Heijnen, VCG, Schroder, CP, Linn, SCC & 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, no. 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: the GELATO trial

AU - Voorwerk, Leonie

AU - Isaeva, Olga I. I.

AU - Horlings, Hugo M. 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. 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. S.

AU - de Visser, Karin E. E.

AU - Schumacher, Ton N. N.

AU - Blank, Christian U. U.

AU - Wessels, Lodewyk F. A.

AU - Jager, Agnes

AU - Tjan-Heijnen, Vivianne C. G.

AU - Schroder, Carolien P.

AU - Linn, Sabine C. C.

AU - Kok, Marleen

PY - 2023/4/1

Y1 - 2023/4/1

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 (), 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 (), 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.

KW - LOCALLY RECURRENT

KW - CARCINOMA

KW - EXPRESSION

KW - IMMUNOTHERAPY

KW - CHEMOTHERAPY

KW - MULTICENTER

KW - SIGNATURES

KW - SURVIVAL

KW - FEATURES

KW - CRITERIA

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

IS - 4

ER -