7P Peripheral blood-based biomarkers of prognosis and treatment response in patients with non-small cell lung cancer treated with PD-1 inhibitors

BackgroundImmune checkpoint blockade (ICB) targeting programmed cell death protein 1 and cytotoxic T lymphocyte-associated protein 4 has achieved modest clinical activity as salvage therapy in relapsed small cell lung cancer (SCLC). We conducted this signal-finding study to assess the efficacy of ICB with or without radiation in relapsed SCLC.MethodsPatients with relapsed SCLC and ≤2 previous lines of therapy were randomized to (1) arm A: durvalumab (D) 1500 mg/tremelimumab (T) 75 mg (intravenously every 4 weeks without stereotactic body radiation therapy (SBRT)) or (2) arm B: immune-sensitizing SBRT to one selected tumor site (9 Gy × 3 fractions) followed by D/T. Treatment continued until progression or a maximum of 12 months. The co-primary endpoints of the study were overall response rate (ORR) and progression-free survival (PFS). We evaluated circulating lymphocyte repertoire in serial peripheral blood samples and tumor infiltrating lymphocytes (TILs) from on-treatment biopsies as pharmacodynamic markers.ResultsEighteen patients were randomized to arms A and B (n=9 each): median age 70 years; 41.2% women. The median PFS and ORR were 2.1 months and 0% in arm A and 3.3 months and 28.6% in arm B. The median overall survival (OS) was 2.8 months in arm A and 5.7 months in arm B (p=0.3772). Pooled efficacy of D/T±SBRT in 15 Response evaluation criteria in solid tumors (RECIST) evaluable patients across both arms showed the best ORR in terms of partial response in 13.3%, stable disease in 26.6% and progressive disease in 60.0%; the overall median PFS and OS were 2.76 and 3.9 months. The most common adverse events were grade 1 fatigue (66%) and grade 1 elevated amylase (56%) in arm A, and grade 1 fatigue (56%) and pain (44%) in arm B. There was a significant increase in activated CD8(+)ICOS+ T cells (p=0.048) and a reduction in naïve T cells (p=0.0454) in peripheral blood following treatment, along with a significant amount of activated CD8+ICOS+ T cells in TILs from responders.ConclusionsThe D/T combination with and without SBRT was safe but did not show sufficient efficacy signal in relapsed SCLC. Changes in peripheral blood lymphocyte and TILs were consistent with an immunologic response.Trial registration numberNCT02701400.

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Serum human epididymis protein 4 is associated with the treatment response of concurrent chemoradiotherapy and prognosis in patients with locally advanced non-small cell lung cancer

Clinical & Translational Oncology ◽

10.1007/s12094-015-1375-y ◽

2015 ◽

Vol 18 (4) ◽

pp. 375-380 ◽

Cited By ~ 8

Author(s):

W.-G. Lan ◽

Y.-Z. Hao ◽

D.-H. Xu ◽

P. Wang ◽

Y.-L. Zhou ◽

...

Keyword(s):

Lung Cancer ◽

Small Cell Lung Cancer ◽

Treatment Response ◽

Cell Lung Cancer ◽

Concurrent Chemoradiotherapy ◽

Locally Advanced ◽

Small Cell ◽

Small Cell Lung ◽

Human Epididymis Protein 4 ◽

Human Epididymis

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The clinical significance of tertiary lymphoid structure and its relationship with peripheral blood characteristics in patients with surgically resected non-small cell lung cancer: a single-center, retrospective study

Cancer Immunology Immunotherapy ◽

10.1007/s00262-021-03067-3 ◽

2021 ◽

Author(s):

Mitsuro Fukuhara ◽

Satoshi Muto ◽

Sho Inomata ◽

Hikaru Yamaguchi ◽

Hayato Mine ◽

...

Keyword(s):

Lung Cancer ◽

Retrospective Study ◽

Small Cell Lung Cancer ◽

Clinical Significance ◽

Cell Lung Cancer ◽

Peripheral Blood ◽

Small Cell ◽

Single Center ◽

Small Cell Lung ◽

Blood Characteristics

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Changes of Tumor Size and Tumor Contrast Enhancement during Radiotherapy for Non-small-cell Lung Cancer May Be Suggestive of Treatment Response

Journal of Radiation Research ◽

10.1269/jrr.11176 ◽

2012 ◽

Vol 53 (2) ◽

pp. 326-332 ◽

Cited By ~ 3

Author(s):

Hiroshi OKADA ◽

Shigeto HONTSU ◽

Sachiko MIURA ◽

Isao ASAKAWA ◽

Tetsuro TAMAMOTO ◽

...

Keyword(s):

Lung Cancer ◽

Small Cell Lung Cancer ◽

Treatment Response ◽

Contrast Enhancement ◽

Cell Lung Cancer ◽

Tumor Size ◽

Small Cell ◽

Small Cell Lung

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Monitoring Treatment Response to Erlotinib in EGFR-mutated Non–small-cell Lung Cancer Brain Metastases Using Serial O-(2-[18F]fluoroethyl)-L-tyrosine PET

Clinical Lung Cancer ◽

10.1016/j.cllc.2018.10.011 ◽

2019 ◽

Vol 20 (2) ◽

pp. e148-e151 ◽

Cited By ~ 3

Author(s):

Diana S.Y. Abdulla ◽

Matthias Scheffler ◽

Vanessa Brandes ◽

Maximilian Ruge ◽

Sabine Kunze ◽

...

Keyword(s):

Lung Cancer ◽

Brain Metastases ◽

Small Cell Lung Cancer ◽

Treatment Response ◽

Cell Lung Cancer ◽

Small Cell ◽

Small Cell Lung ◽

Monitoring Treatment ◽

Egfr Mutated ◽

Monitoring Treatment Response

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Detection of micrometastases in peripheral blood of non-small cell lung cancer with a refined immunomagnetic nanoparticle enrichment assay

International Journal of Nanomedicine ◽

10.2147/ijn.s24731 ◽

2011 ◽

pp. 2175 ◽

Cited By ~ 6

Author(s):

Qing Li ◽

Hui Qi ◽

Han-Xin Zhou ◽

Chun-Yan Deng ◽

...

Keyword(s):

Lung Cancer ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Peripheral Blood ◽

Small Cell ◽

Small Cell Lung

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Circulating mRNA Expression of astrocyte-Elevated Gene-1 Associated with Treatment Response and Survival in Non-Small Cell Lung Cancer Patients Treated with Pemetrexed

10.21203/rs.3.rs-472588/v1 ◽

2021 ◽

Author(s):

You-Lung Chang ◽

Yen-Fu Chen ◽

Ying-Yin Chen ◽

Shih-Chieh Chang ◽

Cheng-Yu Chang ◽

...

Keyword(s):

Lung Cancer ◽

Small Cell Lung Cancer ◽

Mrna Expression ◽

Treatment Response ◽

Cell Lung Cancer ◽

Advanced Nsclc ◽

Small Cell ◽

Small Cell Lung ◽

Cox Regression Analysis ◽

Nsclc Patients

Abstract Backgrounds: Astrocyte-elevated gene-1 (AEG-1) functions as an oncogene and regulates angiogenesis in non-small cell lung cancer (NSCLC). In this prospective study, we assessed the values of plasma AEG-1 mRNA expression by liquid biopsy associated with tumor response and survival in NSCLC patients treated with pemetrexed. Methods: Patients diagnosed advanced NSCLC were enrolled to be treated with pemetrexed combined platinum as first-line chemotherapy. All patients underwent blood sampling before any cancer treatment (C0) and at first response evaluation after two cycles (C2) treatments. Response to chemotherapy and survival were assessed. Plasma mRNA was extracted from peripheral blood mononuclear cell (PBMC) and quantification of RNA was performed by real-time PCR.Results: A total of 50 patients with advanced NSCLC were included and 13 of 50 patients combined with bevacizumab. In patient groups of SD (n = 13) and PD (n = 10), the plasma mRNA of AEG-1, thymidylate synthase (TS) and CK19 were elevated significantly at C2 compared to patients in treatment response group (PR, n = 27) (PR v.s. SD or PD, AEG-1: 1.22 ± 0.80 v.s. 4.51 ± 15.45, p = 0.043). NSCLC patients had elevated AEG-1 (AEG-1 ≥ 2) after 2-cycle chemotherapy had shorter PFS and OS (high AEG-1 v.s. low AEG-1, median, PFS: 5.5 v.s. 11.9 months, p = 0.021; OS: 25.9 v.s. 40.8 months, p = 0.019, respectively). In Cox regression analysis, increased plasma mRNA expression of AEG-1indicated poor prognosis in survival.Conclusion: Circulating mRNA concentration of AEG-1 could be a predictive and prognostic biomarker in NSCLC patients treated with pemetrexed. Increased expression of AEG-1 contributed to the chemoresistance and caused lung cancer progression.

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