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

Nat Cancer. 2023 Apr;4(4):535-549. doi: 10.1038/s43018-023-00542-x. Epub 2023 Apr 10.

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.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • B7-H1 Antigen
  • Carboplatin / therapeutic use
  • Carcinoma, Lobular* / drug therapy
  • Carcinoma, Lobular* / pathology
  • Humans
  • Triple Negative Breast Neoplasms* / drug therapy
  • Triple Negative Breast Neoplasms* / pathology

Substances

  • B7-H1 Antigen
  • Carboplatin

Associated data

  • ClinicalTrials.gov/NCT03147040