PD-L1 immune cell expression levels and clinical outcomes in advanced triple-negative breast cancer treated with atezolizumab.

Authors

null

Tanja Ovcaricek

Division of Medical Oncology, Institute of Oncology Ljubljana, Ljubljana, Slovenia

Tanja Ovcaricek , Luka Dobovisek , Gorana Gasljevic , Dimitar Stefanovski , Simona Borstnar

Organizations

Division of Medical Oncology, Institute of Oncology Ljubljana, Ljubljana, Slovenia, Department of Pathology, Institute of Oncology Ljubljana, Ljubljana, Slovenia

Research Funding

No funding received

Background: Treatment with immune checkpoint inhibitors (ICI) has become a standard of care for metastatic PD-L1 positive TNBC patients and PD-L1 has emerged as an important predictive biomarker. Predictive differences of PD-L1 were found in response to immunotherapy in different studies. Alterations in DNA repair pathways (aDDR) have also been investigated as a predictive biomarker for ICI due to the increased mutations and neoantigen production. Real-world data regarding outcomes of treatment of metastatic (m)TNBC patients (pts) with ICI and predictive value of PD-L1 and aDDR is lacking. In this study PD-L1 and aDDR were evaluated for association with clinical benefit of treatment with atezolizumab and nab-paclitaxel (A+nP) in PD-L1 positive mTNBC patients treated in routine clinical practice. Methods: Medical records from 41 PD-L1 positive mTNBC patients consecutively treated with A+nP at Oncology Institute Ljubljana between April 2019 and October 2021 were collected for the present study. PD-L1 expression was assessed on immune cells (IC) as percentage of tumor area using VENTANA SP142 PD-L1 IHC assay (<1% [PD-L1 negative] vs. ≥1% [PD-L1 positive). Patients were divided into 2 subgroups based on PD-L1 status, high (PD-L1≥ 5%) and low (PD-L1 ≥1% and <5%). Germline alteration status in DDR genes was determined on blood samples. We used Kaplan-Meier survival curves to calculate median (m) PFS and OS . The prognostic impact of PD-L1exspresion levels and aDDR was calculated using Cox model. Results: Median follow up of the study was 22 months. Majority of patients had low PD-L1 status (25/41, 61%) and 54% of evaluable patients (15/28) were found to harbor deleterious alterations in DDR genes, of them BRCA1 in 9 pts, BRCA2 in 2 pts, and PALB2, CHEK2, CHD1, RAD51D in 1 pts. Median PFS in the entire cohort was 8.26 months; 95% CI (3.54-12.98) and mOS 20.49 months; 95% CI (11.3-29.7). Significant survival benefit was observed among patients with high PD-L1 status treated with A+nP. No difference in survival was found in patients harbouring germline mutations (aDDR positive) versus without mutations (Table). Conclusions: PD-L1 positive mTNBC patients with high PD-L1 status (≥5%) had almost three times less risk of progression and death compared to low PD-L1 status (≥1% and <5%). Presence of aDDR showed no effect on disease outcome.

Outcomes with A+nP according to PD-L1 and aDDR status.

mPFS PD-L1 low vs high
4.1 vs 12.8 months, p=0.012, HR: 2.96 (95% CI 1.22-7.17)
mOS PD-L1 low vs high
18.4 vs 25.9 months, p=0.041, HR: 2.79 (95% CI 1.00-7.77)
mPFS aDDR negative vs positive
4.1 vs 5.9 months, p=0.82, HR: 0.90 (0.49-2.10)
mOS aDDR negative vs positive
18.4 vs 13.1 months, p=0.61, HR: 0.78 (0.30-2.02)

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Abstract Details

Meeting

2022 ASCO Annual Meeting

Session Type

Publication Only

Session Title

Breast Cancer—Metastatic

Track

Breast Cancer

Sub Track

Triple-Negative

Citation

J Clin Oncol 40, 2022 (suppl 16; abstr e13066)

DOI

10.1200/JCO.2022.40.16_suppl.e13066

Abstract #

e13066

Abstract Disclosures

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