Efficacy of PD-L1 Blockade in Combination With Carboplatin as Immune Induction in Patients With Metastatic Lobular Breast Cancer
abstract
This abstract is available on the publisher's site.
Access this abstract nowInvasive 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.
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Additional Info
Disclosure statements are available on the authors' profiles:
PD-L1 blockade in combination with carboplatin as immune induction in metastatic lobular breast cancer: the GELATO trial
Nat Cancer 2023 Apr 01;4(4)535-549, L Voorwerk, OI Isaeva, HM Horlings, S Balduzzi, M Chelushkin, NAM Bakker, E Champanhet, H Garner, K Sikorska, CE Loo, I Kemper, IAM Mandjes, M de Maaker, JJL van Geel, J Boers, M de Boer, R Salgado, MGJ van Dongen, GS Sonke, KE de Visser, TN Schumacher, CU Blank, LFA Wessels, A Jager, VCG Tjan-Heijnen, CP Schröder, SC Linn, M KokFrom MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
There is a definite need to conduct more studies, specifically among patients with invasive lobular breast cancer (ILC). It is unusual to observe triple-negative disease as a prognostic factor. Typically, ILC is HR+ and HER2−. Perhaps a larger-scale study can be done by opening up this research to more cancer centers in order that a bigger sample size can be obtained. By doing so, clinicians can learn more about the impact of these drug selections on metastatic ILC treatment. Additionally, when compared with invasive ductal carcinoma, ILC is known for usually growing more slowly and traveling to different organs, such as the uterus, ovaries, intestines, and stomach. It would be interesting to determine in a larger study whether or not these drugs are effective in shrinking the tumors in these specific organs.