1760MO - Impact of immune checkpoint blockade therapy according to CD274 copy number alterations: A retrospective study in the ProfiLER cohort

Background

Immune checkpoint therapy has led to important clinical advances in cancer treatment. Effectiveness of blocking the PD-L1/PD-1 signaling pathway was first correlated to PD-L1 expression with a predictive power that varies substantially between studies. Exploratory analyses of the SAFIR02-Breast study identified CD274 (PD-L1 gene) gain/amplification as a potential predictive biomarker for immune checkpoint blockade drugs (ICBDs) response in triple negative breast cancer patients. In order to determine if CD274 gain/amplification could be an agnostic predictive biomarker, we collected CD274 copy number alterations (CNA) and ICBDs treatment status in the ProfiLER cohort.

Methods

Among the 2962 patients included in the ProfiLER cohort, we selected (i) the subgroup of 285 patients whose tumour had CD274 amplification/gain and (ii) the subgroup of 144 who received ICBD and for which we had the CD274 copy number alteration (CNA) status. Then we assessed in the first group tumour evolution as a function of exposition to ICBD, and, in the second group, we compared clinical response to ICBD according to CD274 CNA.

Results

In the 285 patients with CD274 gain/amplification, median overall survival (OS) from metastatic relapse was 36.7 months in those who received ICBDs and 28 months in those who did not; hazard ratio (HR) 1.52, 95 % confidence interval (CI) [1.05-2.18], p=0.024. Among the 144 patients who did receive ICBD and for which we had the somatic CD274 CNA status, median OS was 15.2 months in the CD274 gain/amplification group compared with 9.7 months in the CD274 normal/loss group; HR 0.63, 95% CI [0.42-0.95], p=0.026. In the most prevalent cohort; head and neck carcinoma (n = 90); median OS was 28.6 months in the CD274 gain/amplification subgroup as compared with 9.1 months in the CD274 normal/loss subgroup; HR 0.40, 95% CI [0.21-0.76], p=0.004.

Conclusions

In this retrospective study, CD274 CNA gain/amplification is associated with OS improvement when patients are treated with ICBD. Further prospective studies are needed to confirm CD274 gain/amplification as a predictive biomarker for ICBDs response.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

Centre Léon Berard.

Funding

Has not received any funding.

Disclosure

P. Heudel: Non-Financial Interests, Other: Pfizer; Financial Interests, Research Grant: Novartis; Financial Interests, Research Grant: Roche; Non-Financial Interests, Other: Novartis; Financial Interests, Other: Mylan; Financial Interests, Other: Pierre Fabre; Financial Interests, Other: Seagen; Financial Interests, Other: Amgen; Non-Financial Interests, Other: AstraZeneca. O. Tredan: Financial Interests, Other, personal fees: Roche; Financial Interests, Other, personal fees: MSD-Merck; Financial Interests, Other, personal fees: AstraZeneca; Financial Interests, Other, personal fees: Pfizer; Financial Interests, Other, personal fees: Lilly; Financial Interests, Other, personal fees: Seagen; Financial Interests, Other, personal fees: Daiichi Sankyo; Financial Interests, Other, personal fees: Eisai; Financial Interests, Other, personal fees: Pierre Fabre; Financial Interests, Research Grant: Roche; Financial Interests, Research Grant: MSD-Merck; Financial Interests, Research Grant: BMS. T. Filleron: Non-Financial Interests, Other, Consulting: Cellectics. F. André: Financial Interests, Invited Speaker, and research funding: Roche; Financial Interests, Invited Speaker, and research funding: AstraZeneca; Financial Interests, Invited Speaker, and research funding: Daiichi; Financial Interests, Invited Speaker, and research funding: Pfizer; Financial Interests, Invited Speaker, and research funding: Novartis; Financial Interests, Invited Speaker, and research funding: Lilly. T. Bachelot: Financial Interests, Invited Speaker, and research funding: Roche; Financial Interests, Invited Speaker, and research funding: Novartis; Financial Interests, Invited Speaker, and research funding: Pfizer; Financial Interests, Invited Speaker, and research funding: Seattle Genetic; Financial Interests, Invited Speaker, and research funding: Lilly; Financial Interests, Invited Speaker, and research funding: AstraZeneca. All other authors have declared no conflicts of interest.