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

Autor: Voorwerk L; Division of Tumor Biology and Immunology, The Netherlands Cancer Institute, Amsterdam, the Netherlands., Isaeva OI; Division of Tumor Biology and Immunology, The Netherlands Cancer Institute, Amsterdam, the Netherlands., Horlings HM; Department of Pathology, The Netherlands Cancer Institute, Amsterdam, the Netherlands., Balduzzi S; Department of Biometrics, The Netherlands Cancer Institute, Amsterdam, the Netherlands., Chelushkin M; Division of Tumor Biology and Immunology, The Netherlands Cancer Institute, Amsterdam, the Netherlands.; Division of Molecular Carcinogenesis, The Netherlands Cancer Institute, Amsterdam, the Netherlands., Bakker NAM; Division of Tumor Biology and Immunology, The Netherlands Cancer Institute, Amsterdam, the Netherlands.; Oncode Institute, Utrecht, the Netherlands., Champanhet E; Division of Tumor Biology and Immunology, The Netherlands Cancer Institute, Amsterdam, the Netherlands., Garner H; Division of Tumor Biology and Immunology, The Netherlands Cancer Institute, Amsterdam, the Netherlands.; Oncode Institute, Utrecht, the Netherlands., Sikorska K; Department of Biometrics, The Netherlands Cancer Institute, Amsterdam, the Netherlands., Loo CE; Department of Radiology, The Netherlands Cancer Institute, Amsterdam, the Netherlands., Kemper I; Department of Medical Oncology, The Netherlands Cancer Institute, Amsterdam, the Netherlands., Mandjes IAM; Department of Biometrics, The Netherlands Cancer Institute, Amsterdam, the Netherlands., de Maaker M; Division of Molecular Pathology, The Netherlands Cancer Institute, Amsterdam, the Netherlands., van Geel JJL; Department of Medical Oncology, University Medical Center Groningen, Groningen, the Netherlands., Boers J; Department of Medical Oncology, University Medical Center Groningen, Groningen, the Netherlands., de Boer M; Department of Medical Oncology, GROW, Maastricht University Medical Center, Maastricht, the Netherlands., Salgado R; Department of Pathology, GZA-ZNA hospitals, Antwerp, Belgium.; Division of Research, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia., van Dongen MGJ; Department of Medical Oncology, The Netherlands Cancer Institute, Amsterdam, the Netherlands., Sonke GS; Department of Medical Oncology, The Netherlands Cancer Institute, Amsterdam, the Netherlands., de Visser KE; Division of Tumor Biology and Immunology, The Netherlands Cancer Institute, Amsterdam, the Netherlands.; Oncode Institute, Utrecht, the Netherlands.; Department of Immunology, Leiden University Medical Center, Leiden, the Netherlands., Schumacher TN; Oncode Institute, Utrecht, the Netherlands.; Division of Molecular Oncology and Immunology, The Netherlands Cancer Institute, Amsterdam, the Netherlands.; Department of Hematology, Leiden University Medical Center, Leiden, the Netherlands., Blank CU; Department of Medical Oncology, The Netherlands Cancer Institute, Amsterdam, the Netherlands.; Division of Molecular Oncology and Immunology, The Netherlands Cancer Institute, Amsterdam, the Netherlands., Wessels LFA; Division of Molecular Carcinogenesis, The Netherlands Cancer Institute, Amsterdam, the Netherlands.; Oncode Institute, Utrecht, the Netherlands., Jager A; Department of Medical Oncology, Erasmus Medical Center, Rotterdam, the Netherlands., Tjan-Heijnen VCG; Department of Medical Oncology, GROW, Maastricht University Medical Center, Maastricht, the Netherlands., Schröder CP; Department of Medical Oncology, The Netherlands Cancer Institute, Amsterdam, the Netherlands.; Department of Medical Oncology, University Medical Center Groningen, Groningen, the Netherlands., Linn SC; Department of Medical Oncology, The Netherlands Cancer Institute, Amsterdam, the Netherlands.; Division of Molecular Pathology, The Netherlands Cancer Institute, Amsterdam, the Netherlands.; Department of Pathology, University Medical Center Utrecht, Utrecht, the Netherlands., Kok M; Division of Tumor Biology and Immunology, The Netherlands Cancer Institute, Amsterdam, the Netherlands. m.kok@nki.nl.; Department of Medical Oncology, The Netherlands Cancer Institute, Amsterdam, the Netherlands. m.kok@nki.nl.
Jazyk: angličtina
Zdroj: Nature cancer [Nat Cancer] 2023 Apr; Vol. 4 (4), pp. 535-549. Date of Electronic Publication: 2023 Apr 10.
DOI: 10.1038/s43018-023-00542-x
Abstrakt: 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.
(© 2023. The Author(s).)
Databáze: MEDLINE
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