Poster viewing and lunch

37P - Enhanced tumor-immunity drives resistance to CDK4/6 inhibitors in advanced breast cancer (ID 257)

Lecture Time
12:15 - 12:15
Session Name
Poster viewing and lunch
Room
Exhibition area
Date
Fri, 12.05.2023
Time
12:15 - 13:00
Speakers
  • Milana A. Bergamino (L'Hospitalet de Llobregat, Spain)
Authors
  • Milana A. Bergamino (L'Hospitalet de Llobregat, Spain)
  • Sviatoslav Checkhun (Badalona, Spain)
  • Angelica Ferrando Diez (Badalona, Spain)
  • Beatriz Cirauqui Cirauqui (Badalona, Ba, Spain)
  • Iris Teruel-Garcia (Badalona, Spain)
  • Margarita Romeo Marin (Badalona, Ba, Spain)
  • Vanesa Quiroga (Badalona, Spain)
  • Anna Pous (Badalona, Spain)
  • Assumpcio Lopez Paradis (Badalona, Spain)
  • Eva Riveira-Muñoz (Badalona, Spain)
  • Ester Ballana (Badalona, Spain)
  • Mireia Margeli Vila (Badalona, Spain)

Abstract

Background

Cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) have led to a paradigm shift in the treatment of hormone receptor-positive (HR+)/HER2- advanced breast cancer (ABC). Prior data has suggested a key role of tumor immunity in CDK4/6i success. We investigate immune-mediated resistance to CDK4/6i treatment.

Methods

63 samples from 55 patients with HR+HER2- ABC treated with CDK4/6i were recruited (34 primary, 21 metastatic (M1) and 8 paired biopsies). Gene expression (GE) was assessed using NanoString Breast Cancer 360™, including intrinsic subtype (IS). Patients were stratified in good/poor responders (GR/PR), considering hormone sensitivity and progression-free survival (PFS) data from pivotal studies (GR n=38, 66.5%). Multiple t-tests comparisons were used to identify GE differences and Kaplan Meier and Cox regression models for survival.

Results

GE comparisons between primary and M1 biopsies showed significantly higher expression of immune-related features and oestrogen receptor (ER)-signalling in primary biopsies (T.test; p-value<0.05). GE profiles between response groups were compared to identify mechanisms of resistance to CDK4/6i. Most tumors were luminal A or B (n=23, 36.5% each). The IS were not significantly associated with response (Chi-square p>0.05). High GE of tumor-immunity related signatures such as macrophages, PD-L2, inflammatory-chemokines, IDO1, and T-regs were associated with reduced efficacy of CDK4/6i (mean log2FC 0.5; p<0.05). Survival analysis in first-line CDK4/6i confirmed longer PFS within patients with luminal tumours (p=0.02). Type of M1 (visceral or non-visceral) and type of response (PR vs GR) were also associated with significantly shorter PFS and overall survival (OS) (p<0.05), remaining as independent predictors after adjustment by the standard clinico-pathological variables. High expression of macrophages signature (HR: 3.14; p=0.03) and other genes related to immunity/inflammation (CD68, CD163, CCR1 or CDC25B) were also associated with worse OS (HR 1.8-6.1; p-value<0.05).

Conclusions

Immune function plays a key role in tumor evolution and CDK4/6i efficacy. Further investigation of immune-tumor crosstalk and the role of immunotherapy in this setting is needed to improve CDK4/6i efficacy.

Legal entity responsible for the study

ICO Badalona.

Funding

Investigational grants: 1) ISCIII-FIS (CM20/00027 and MSII19/00012). Dates 2020- 2022; 2) ISCIII-FIS (PI17/00624 and PI21/00642). Dates: 2020-2023. Collaborations: 1) Pfizer grant (Pfizer, SA; Spain). Dates 2020-2023; 2) NanoString Translational Research Request. Dates: 13/01/2020-10/12/2022.

Disclosure

M.A. Bergamino: Financial Interests, Personal, Sponsor/Funding: ESAI, Novartis. E. Felip Falgas: Financial Interests, Personal, Sponsor/Funding: Novartis, Pfeizzer, Lilly, Roche. A. Ferrando Diez: Financial Interests, Personal, Invited Speaker: MSD; Financial Interests, Personal, Sponsor/Funding: MSD, Lilly, Roche, Merck. M. Romeo Marin: Financial Interests, Personal, Sponsor/Funding: GSK; Financial Interests, Personal, Research Grant: MSD, Clovis; Financial Interests, Personal, Speaker’s Bureau: AZ. A. Pous: Financial Interests, Personal, Sponsor/Funding: Lilly, Roche. M. Margeli Vila: Financial Interests, Personal, Sponsor/Funding: Novartis, Pfizer, Lilly, Gilead, PiereFabre; Financial Interests, Institutional, Research Grant: Pfizer. All other authors have declared no conflicts of interest.

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