Genomic landscape and peripheral blood biomarkers of advanced triple-negative breast cancer treated with immune checkpoint blockade: An exploratory analysis of the TQB2450-Ib-07 trial.

Authors

Yiqun Han

Yiqun Han

National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences, Beijing, China

Yiqun Han , Jiayu Wang , Tao Sun , Quchang Ouyang , Jianwen Li , Binghe Xu

Organizations

National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences, Beijing, China, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China, Liaoning Cancer Hospital, Shenyang, China, Department of Breast Cancer Medical Oncology, Hunan Cancer Hospital, Changsha, China, Geneplus-Beijing Institute, Beijing, China

Research Funding

Pharmaceutical/Biotech Company

Background: Immune checkpoint inhibitor (ICI) has emerged as a novel therapeutic option for advanced triple-negative breast cancer (aTNBC). However, no robust biomarker indicative of clinical outcomes has been identified. Herein, we portraited the genomic landscape and explored the biomarkers for patients with aTNBC receiving ICI-based therapy. Methods: This is a prospective, multicenter, phase 1b clinical trial (NCT03855358) to assess the efficacy and safety profiles of TQB2450, a humanized monoclonal PD-L1 antibody, plus anlotinib in pretreated TNBC. Eligible patients undergo liquid biopsy at baseline and the timepoint of disease progression. NGS-based assay was performed based on circulating tumor DNA (ctDNA) in the bloodstream. Meanwhile, results of laboratory blood tests were dynamically collected and blood markers, including neutrophil to lymphocyte ratio (NLR), lymphocyte to monocyte ratio (LMR), and platelet to lymphocyte ratio (PLR), were successively evaluated. The primary endpoints were progression-free survival (PFS) and clinical efficacy assigned via guidelines for response criteria for use in trials testing immunotherapies (iRECIST). Results: Between May 29, 2019, and December 31, 2020, 34 patients with aTNBC were enrolled. Gene alternations primarily comprised mutation, amplification, or deletion of TP53, MLL3, DNMT3A, PI3KCA, EP300, PTEN, LRP1B, MDM2, and NCOR1. The median maximum somatic allele frequency (MSAF) was 9.97% significantly indicative of PFS, which was 3.58 months for the MSAF-high group and 13.34 months for the MSAF-low group (P = 3e-04), respectively. Else, a strong association was also signified between MSAF and tumor shrinkage (CR/PR vs. SD/PD, P = 0.012). For blood tumor mutation burden (bTMB), the median was 6.72 muts/Mb, which the bTMB-low group was suggestive of a better PFS (11.09 months vs. 5.52 months, P = 0.007), yet no obvious association existing in terms of clinical response. Dynamic analysis revealed that a decline in MSAF was significantly associated with a better PFS (7.10 months vs. 2.74 months, P = 0.018), while no correlations were detected between bTMB and PFS. Based on NLR week 2/0 of 0.95, PFS was significantly worse in the NLR-low group (11.0 months vs. 3.5 months, P = 0.006) and likely distinguished the clinical response (CR/PR vs. SD vs. PD, P = 0.049; non-PD vs. PD, P = 0.022). Moreover, NLR week 2/0 could notably foretell the clinical response for patients with aTNBC with the AUC of 0.82 (0.61-1.00). No comparable utilities were identified regarding LMR and PLR. Conclusions: For aTNBC treated with ICI, MSAF tended to be a robust indicator for both PFS and clinical response. NLR week 2/0 presented a favorable profile indicative of PFS as well as a strong predictor for clinical responsiveness of patients with aTNBC receiving immune checkpoint blockade. Clinical trial information: NCT03855358.

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Abstract Details

Meeting

2022 ASCO Annual Meeting

Session Type

Poster Session

Session Title

Breast Cancer—Metastatic

Track

Breast Cancer

Sub Track

Triple-Negative

Clinical Trial Registration Number

NCT03855358

Citation

J Clin Oncol 40, 2022 (suppl 16; abstr 1080)

DOI

10.1200/JCO.2022.40.16_suppl.1080

Abstract #

1080

Poster Bd #

458

Abstract Disclosures

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