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

Invasive lobular breast cancer (ILC) is the second most common histological breast cancer subtype but published data on trials specific for ILC are so far lacking. Translational research revealed that a subset of ILCs may be immune-related and more sensitive to DNA-damaging agents such as platinum. In murine ILC models, synergy between immune checkpoint blockade and platinum has been observed. Here, we tested this concept in the phase II, GELATO-trial (NCT03147040), in which patients with metastatic ILC were treated with weekly carboplatin (AUC 1.5) as immune induction treatment for 12 weeks and atezolizumab (PD-L1 blockade; every three weeks) from the third week onwards until disease progression. Four out of 23 evaluable patients had a partial response (17%, 95%CI 5-39%) and two patients had stable disease for at least 24 weeks, resulting in a clinical benefit rate of 26% (95%CI 10-48%). Out of these six patients, four patients had triple-negative ILC (TN-ILC). In serial biopsies of metastatic lesions, we observed higher CD8 T-cell infiltration, expression of immune checkpoints, and exhausted T cells upon carboplatin/PD-L1 blockade. This is the first report of a clinical trial specifically for ILC and we demonstrate promising anti-tumor activity of atezolizumab with carboplatin as immune induction, in particular for TN-ILC. While activity of carboplatin/PD-L1 blockade in classical ER+ ILC was limited, our translational data yield important insights for the design of highly needed clinical trials in ILC.

Type: Other
Archiver: European Genome-Phenome Archive (EGA)

4 Datasets 1 Publication

Click on a Dataset ID in the table below to learn more, and to find out who to contact about access to these data

Dataset ID	Description	Technology	Samples
EGAD00001009834	RNA-Seq data of 46 matched lobular breast cancer metastatic samples obtained from 21 unique patients from GELATO clinical trial assayed at three timepoints: at baseline (directly after patient randomization), pre-atezolizumab (after induction treatment with carboplatin for two weeks) and on atezolizumab (after two cycles of atezolizumab combined with carboplatin). The included raw transcriptome sequencing data in fastq format was generated using Illumina NovaSeq 6000 from fresh frozen material.	Illumina NovaSeq 6000	46
EGAD00001009835	RNA-Seq data of 10 lobular breast cancer primary tumors and 3 local recurrences obtained from 11 unique patients from GELATO clinical trial. The included raw transcriptome sequencing data in fastq format was generated using Illumina NovaSeq 6000 from archived FFPE material.	Illumina NovaSeq 6000	13
EGAD00001009836	Paired-end whole exome sequencing of 10 lobular breast cancer primary tumors, 3 local recurrences and matched normal samples obtained from 10 unique patients from the GELATO clinical trial. The included raw sequencing data in fastq format was generated using Illumina NovaSeq 6000 from archived FFPE material (tumor data) and fresh frozen material (matched normal data).	Illumina NovaSeq 6000	23
EGAD00001009837	Paired-end whole exome sequencing of 19 lobular breast cancer metastatic tumors and matched normal samples obtained from 19 unique patients from the GELATO clinical trial. The included raw sequencing data in fastq format was generated using Illumina NovaSeq 6000 from fresh frozen material.	Illumina NovaSeq 6000	38

Publications	Citations
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, Schröder CP, Linn SC, Kok M. Nat Cancer 4: 2023 535-549	7

Publications

Citations

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, Schröder CP, Linn SC, Kok M. Nat Cancer 4: 2023 535-549