Predictive value of mRNA expression and dynamic changes from immune related biomarkers in liquid biopsies before and after start of pembrolizumab in stage IV non-small cell lung cancer (NSCLC)

e15053 Background: With the introduction of targeted therapies and immunotherapy, molecular diagnostics gained a more profound role in the management of non-small cell lung cancer (NSCLC). Currently, tissue biopsies (TB) are used as primary source for molecular testing and generally require an invasive procedure. The introduction of liquid biopsies (LB) not only decreases patient burden, but it also allows for more frequent testing. Which might be of value in the monitoring of treatment response. This study aimed to systematically search for studies reporting on the use of LB, the correlation between LB and TB, and finally the predictive value in the management of NSCLC. Methods: A systematic literature search was performed using Scopus and PubMed, including results published in English after 01-01-2014. Articles were included when 1) describing the predictive value of a LB with regard to overall and/or progression-free survival, or 2) describing the validity of a marker by comparing LBs to TBs regarding sensitivity, specificity, or concordance. Results: 1705 articles were identified in the search, 1323 articles were excluded after title and abstract screening, leaving 382 articles for full-text evaluation. Of the 137 articles included after full-text evaluation, 78 articles described the validity, and 65 articles described the predictive value of LBs. In studies describing the predictive value of LBs, the majority of articles reported on the predictive value of biomarkers in relation to targeted therapies (n = 31). In studies describing the validity of LBs, the majority of studies report on EGFR mutations including, exon 19 deletion (n = 23) and L858R (n = 26). Looking at the validity of LBs, we saw a large variation in reported sensitivity (range 20-100%), specificity (range 30-100%), and concordance (range 40-99%). Conclusions: Although a variety of blood-based biomarkers has been investigated, most studies have limited their evaluation to sensitivity and specificity of liquid biopsies to determine EGFR mutation status compared to tissue and the subsequent targeting of EGFR tyrosine kinase inhibitors based on the mutation status found in LBs of NSCLC patients. The first adoption of LBs in practice is expected to involve the detection of EGFR mutations by LB analysis in addition to TBs.

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The predictive value of BRCA1 and RAP80 mRNA expression in advanced non-small-cell lung cancer patients treated with platinum-based chemotherapy

Annals of Oncology ◽

10.1093/annonc/mdt063 ◽

2013 ◽

Vol 24 (4) ◽

pp. 1130-1132 ◽

Cited By ~ 11

Author(s):

L. Bonanno ◽

C. Costa ◽

M. Majem ◽

A. Favaretto ◽

M. Rugge ◽

...

Keyword(s):

Lung Cancer ◽

Small Cell Lung Cancer ◽

Mrna Expression ◽

Cancer Patients ◽

Cell Lung Cancer ◽

Predictive Value ◽

Small Cell ◽

Small Cell Lung ◽

Lung Cancer Patients ◽

Platinum Based Chemotherapy

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Cost and survival analysis before and after implementation of Dana-Farber Clinical Pathways for Patients with Stage IV Non-Small Cell Lung Cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.8_suppl.3 ◽

2017 ◽

Vol 35 (8_suppl) ◽

pp. 3-3

Author(s):

Yichen Zhang ◽

Belen Fraile ◽

Carole Kathleen Dalby ◽

Tom Nguyen ◽

Julia Nagle ◽

...

Keyword(s):

Lung Cancer ◽

Small Cell Lung Cancer ◽

Clinical Outcomes ◽

Cell Lung Cancer ◽

Clinical Pathways ◽

Stage Iv ◽

Small Cell ◽

Cost Of Care ◽

Small Cell Lung ◽

Before And After

3 Background: Oncologists face challenges associated with increasing cost and medical complexity. The Dana-Farber Cancer Institute (DFCI) has created a customized clinical pathways program that seeks to prospectively support and guide medical decision-making across our network. It also allows the Institute to track and learn from the medical decisions made. We have analyzed cost and outcomes data from before and after the implementation of Dana-Farber Pathways in our thoracic oncology program. Methods: Our lung cancer group created a customized clinical pathway for the treatment of non-small cell lung cancer (NSCLC). We partnered with Via Oncology to provide a web-based platform for real-time pathway navigation and post-treatment data aggregation. DFCI Pathways for NSCLC went live in January 2014. We identified all patients who were diagnosed with and treated for stage IV NSCLC in 2012 (pre-pathways) and 2014 (post-pathways). Demographics, clinical characteristics, treatments, and clinical outcomes were captured. Costs of care for each patient were determined for one year from the time of diagnosis. Results: We identified a total of 160 Stage IV NSCLC patients diagnosed in 2012, and 210 patients diagnosed in 2014. The pretreatment group had more women (61% vs. 50%) but was otherwise similarly matched in terms of smoking status and presence of targetable changes in EGFR and ALK. The total 12-month cost of care (adjusted for age, sex, race, distance to DFCI, clinical trial enrollment, and EGFR and ALK status) demonstrated a $15,013 savings after the implementation of pathways ($67,050 pre, $52,037 post). Clinical outcomes were not compromised, with no significant difference in median overall survival (10.7 months pre, 11.2 months post; p = 0.08). Conclusions: In an era where comparative outcomes analysis and value assessment are increasingly important, the implementation of a clinical pathways program can provide a means to harness and deploy institutional expertise and track and learn from care decisions. Patients treated after the implementation of a clinical pathways program in lung cancer saw preserved clinical outcomes and a significant decrease in cost of care.

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Dynamic changes in circulating PD-1+CD8+ T lymphocytes for predicting treatment response to PD-1 blockade in patients with non-small cell lung cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.15_suppl.e21690 ◽

2020 ◽

Vol 38 (15_suppl) ◽

pp. e21690-e21690

Author(s):

Chang Gon Kim ◽

Min Hee Hong ◽

Kyung Hwan Kim ◽

Kyoung-Ho Pyo ◽

Chun-Feng Xin ◽

...

Keyword(s):

Lung Cancer ◽

T Lymphocytes ◽

Small Cell Lung Cancer ◽

Treatment Response ◽

Predictive Value ◽

Validation Cohort ◽

Small Cell ◽

Small Cell Lung ◽

Discovery Cohort ◽

Dynamic Changes

e21690 Background: The predictive value of dynamic changes in the expression of programmed cell death-1 (PD-1) among circulating CD8+ T lymphocytes for treatment response to PD-1 inhibitors has not been explored in non-small-cell lung cancer (NSCLC). This study aimed to investigate whether dynamic changes in PD-1+CD8+ T lymphocytes have predictive value with respect to durable clinical benefit (DCB) and survival after PD-1 blockade. Methods: Patients with recurrent and/or metastatic NSCLC treated with PD-1 inhibitors were enrolled between March 2016 and August 2018 (discovery cohort; n = 94). Peripheral blood was obtained immediately before and after one cycle of treatment with PD-1 blockade. Phenotyping of circulating CD8+ T lymphocytes was conducted using multi-color flow cytometry. Predictive values of dynamic changes in circulating PD-1+CD8+ T lymphocytes during the first cycle were validated in an independent cohort (validation cohort; n = 54) of a prospective trial with PD-1 inhibitor (NCT03486119). Results: Circulating PD-1+CD8+ T lymphocytes were enriched with effector/memory populations with elevated expression of activation- and exhaustion-related markers. Reduction in the frequency of PD-1+ cells among CD8+ T lymphocytes after one cycle of treatment was associated with a higher probability of DCB and superior survival outcomes in the discovery cohort. Similar results were obtained in analysis of tumor antigen NY-ESO-1-specific CD8+ T lymphocytes and in the validation cohort. Conclusions: Dynamic changes in circulating PD-1+CD8+ T lymphocytes predict clinical and survival benefit from PD-1 blockade treatment in NSCLC. Thus, tracking these changes may be useful for identifying NSCLC patients who will optimally benefit from the treatment.

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Liquid biopsies for the front line therapy decision in non-small cell lung cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.15_suppl.e21103 ◽

2021 ◽

Vol 39 (15_suppl) ◽

pp. e21103-e21103

Author(s):

Kayla Brice ◽

Luis E. Raez ◽

Katerine Dumais ◽

Delia Wietecha ◽

Alejandro Lopez-Cohen ◽

...

Keyword(s):

Lung Cancer ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Stage Iv ◽

Treatment Decision ◽

Small Cell ◽

Front Line ◽

Small Cell Lung ◽

Liquid Biopsies ◽

Final Treatment

e21103 Background: Current literature has demonstrated non-inferiority of liquid biopsies relative to tissue genotyping to identify detectable biomarkers in patients with metastatic non-small cell lung cancer (NSCLC). However, liquid biopsies have the ability to report next generation sequencing (NGS) results faster than tissue NGS. Tissue NGS has the disadvantage that depends on the amount of tumor available after the original pathology report is issued and it is not infrequent that there is an insufficient sample for NGS (QNS). Another major disadvantage is that the results of tissue NGS usually take longer than blood NGS due to the process of requesting and shipping tissue. This study aimed to illustrate that liquid biopsies can be the new standard in front line decision making for patients with stage IV NSCLC when compared with tissue NGS. Methods: This was a retrospective review of adult patients within the Memorial Cancer Institute who were diagnosed with stage IV NSCLC and received, at the same time, a tissue and liquid biopsy between July 1, 2015 and June 30, 2020. Patients were excluded if biopsies were not performed within one month apart or the treatment decision was not determined. Data collected utilizing the electronic medical record included: demographics, biopsy turnaround time, biopsy type used to make the final treatment decision, insufficient tissue samples, date of disease progression and death, and detection of genomic biomarkers. Descriptive statistics and logistic regression analysis were calculated for all demographic and clinical outcomes. Results: One hundred and thirty-one patients were evaluated. Of the evaluated patients, 53% were female, 47% were men, 74% had a smoking history and 26% never smoked. Non-Hispanic Whites were 56%, Hispanics 29%, and African Americans 8%. The average age at diagnosis was 66 ± 13 years of age. Of the 122 tumors where genomic biomarkers were detected by liquid NGS, 75% had actionable genetic aberrations (EGFR, ALK, ROS-1, NTRK 1-3, BRAFv600, RET, METexon14skipping). While only 53% had actionable genetic alterations out of 111 tumors with detectable mutations by tissue NGS. Final treatment decisions were made in 70% of the patients based on the results of the liquid NGS that generally arrived first and only 30% of the treatment decisions on the tissue NGS. The median time to start therapy was 9 days with liquid NGS vs 33.5 days with tissue NGS. More than 90% of the patients with an actionable mutation with liquid NGS were able to start therapy within 11 ± 5 days. Progression free survival was similar for patients in which the treatment decision was based on liquid NGS vs tissue NGS (p = 0.99). Conclusions: In patients with stage IV NSCLC, NGS done by liquid biopsies may be used as the standard of care to make the front line therapeutic decision in patients with NSCLC. A prospective study with a larger sample is probably needed to validate these results.

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