Non-squamous Cell Lung Cancer Patients Research Articles

Impact of tissue biomarker testing by in-house platform on result times in metastatic non-small cell lung cancer.

49 Background: Biomarker testing for actionable mutations is standard of care for patients diagnosed with metastatic non-small cell, non-squamous cell lung cancer. However, testing via third-party laboratories can take weeks to result, leading to treatment decision delays identified at our own institution. Methods: We conducted a retrospective chart review of metastatic non-small cell, non-squamous cell lung cancer patients treated at Orlando Regional Medical Center before (6/1/2021-5/31/2022) as well as after (1/1/2023-5/31/2023) the initiation of in-house next generation sequencing (NGS) tissue testing using Genexus. Endpoints included average and median time to result of plasma and tissue NGS both before and after initiation of in-house molecular testing. An independent two sample t-test was conducted with p<0.05 considered significant. Results: A total of 49 and 18 patients were included pre and post initiation of in house NGS, respectively. For patients with tissue testing, the average time from collection to result was 31.3 versus 13.9 days (p<0.01), median 29 versus 7 days. For patients who underwent plasma testing (n=49, n=10), average time from collection to result was 13.3 versus 9.6 days (p=0.38), median 9 versus 9 days. Conclusions: Time to comprehensive tissue testing result significantly decreased after the commencement of in-house NGS. Rapid turnaround time allows clinicians to select appropriate first-line treatment without delay in care. Further efforts are needed to expedite molecular testing in all stages of non-small cell lung cancer and evaluate sequential versus concurrent plasma and tissue testing.

Long-term exposure to pemetrexed induces chronic renal dysfunction in patients with advanced and recurrent non-squamous cell lung cancer: a retrospective study

BackgroundPemetrexed (PEM) is administered over a long term to patients with non-squamous cell lung cancer as a maintenance therapy after platinum combination induction chemotherapy. Although decreased renal function owing to long-term PEM exposure has been reported, changes in the renal function of individual patients have not been reported. This study aimed to evaluate serum creatinine (Scr) in individual patients over time and determine whether long-term PEM exposure contributed to increased Scr.MethodsA retrospective study was performed using 90 non-squamous cell lung cancer patients, who had received maintenance therapy with PEM ± bevacizumab (BEV) after carboplatin + PEM ± BEV therapy at the Sapporo Minami-Sanjo Hospital from February 2012 to February 2019. Using Scr at the start of induction chemotherapy as the baseline, we calculated the correlation coefficient (r) of the rate of Scr change in an individual patient and the number of treatment courses to divide patients into two groups for comparison: patients with + 0.4 < r ≦ + 1.0 and an observed positive correlation (the r+0.4< group), and patients with − 1.0 ≦ r ≦ + 0.4 and no observed positive correlation (the r+0.4≧ group).ResultsStatistically significant differences between the r+0.4< group and the r+0.4≧ group were observed for the following parameters: the median cumulative dose of PEM (interquartile range) [9100 (6365, 12,260) mg/body vs. 5600 (4140, 7440) mg/body, P < 0.01]; the number of patients taking nonsteroidal anti-inflammatory drugs at the start of treatment [15 patients (31%) vs. 3 patients (7%), P < 0.01]; and the median number of treatment courses starting from induction chemotherapy [11 (8, 14) courses vs. 8 (6, 11) courses, P < 0.01]. Next, the results of univariate and multivariate analyses demonstrated that the cumulative dose of PEM (≧ 7000 mg/body vs < 7000 mg/body, OR 2.40; 95% CI, 1.22–4.75, P = 0.01) was an independent explanatory variable of the r+0.4< group.ConclusionsLong-term PEM exposure may induce chronic renal dysfunction. Hence, maintaining kidney function during PEM treatment by reducing the use of combination drugs and the risk of other renal dysfunctions, such as dehydration, may help patients continue therapy and contribute to their long-term survival.

Characterizing biomarker testing over time in lung cancer patients using oncology electronic medical records (EMR).

e20056 Background: This study characterizes biomarker testing over time in Non-Small Cell Lung Cancer (NSCLC) patients treated within a clinical setting. There have been tremendous advances in treatments for NSCLC that target specific biomarkers such as epithelial growth factor receptor (EGFR), anaplastic lymphoma kinase (ALK), and the Programmed cell death-ligand 1 (PD-L1) pathway. As we consider using oncology EMR records for future studies, it is critical to understand the extent to which biomarker testing is conducted in routine care, the extent to which testing has increased, and the types of patients for which it is done. Methods: This is a retrospective observational analysis derived from the COTA Oncology EHR database from January 1, 2015 through December 31, 2017. The data sets generated for the study included all relevant, retrospective patient-level, de-identified data available for patients with lung cancer, including EGFR, ALK, and PD-L1 testing regardless of age, gender, and stage at diagnosis. We examined characteristics associated with each type of test received as well as by those who had received all 3 biomarker tests, 1-2 of the tests, or no biomarker testing. Analyses were conducted using SAS V. 9.1 and stratified by data source. Results: There were 1,891 patients in the COTA database. Among newly diagnosed NSCLC patients, EGFR testing has been consistently conducted in patients during the study period (76 – 86%), while ALK testing [44% in 2015Q1 to 74% in 2017Q4] and PD-L1 testing [12% in 2015Q1 to 77% in 2017Q4] have steadily increased each quarter. Overall, testing was more likely to be conducted in non-squamous cell lung cancer patients, Stage IV lung cancer, and those without a history of smoking. For EGFR, testing was more prevalent among women and young age groups ( &lt; 64 years vs. 65 and older). Conclusions: Biomarker testing has rapidly increased for ALK and PD-L1, which correlates with the uptake of new targeted therapies. Further research could be conducted to understand clinical outcomes associated with this increase in testing as well as the impact on healthcare resource utilization.

Concordance between comprehensive cancer genome profiling in plasma and matched tumor specimens.

e23146 Background: The importance and clinical use of liquid biopsies to identify somatic, targetable alterations in the plasma of cancer patients is steadily increasing. However, their concordance with alterations identified in cancer specimens tested in routine diagnostics is not being monitored. In a cohort of non-squamous cell lung cancer patients, our aim was to systematically compare alterations found by a massively parallel sequencing liquid biopsy assay covering 39 cancer related genes (NEOliquid) with alterations identified by routine diagnostics in a certified central pathology laboratory. Methods: Routine Diagnostics: DNA mutational analysis was performed using cobas or Sanger-Sequencing. Rearrangements were identified using immunohistochemistry or FISH. NEOliquid assay: Cell-free DNA from plasma was subjected to hybrid-capture based next-generation sequencing to detect point mutations, small insertions and deletions, copy number alterations and genomic translocations in 39 clinically relevant genes in a single assay. To evaluate and compare the performance of liquid biopsies, we applied the NEOliquid tests on blood samples of 82 non-squamous NSCLC patients and correlated them with results of routine diagnostics of matched tissue samples. Results: Routine diagnostics for lung cancer related oncogenes (EGFR, ALK, ROS1, KRAS, BRAF) identified a total of 50 somatic alterations of which 37 were point mutations, 11 InDels and 2 gene fusions. NEOliquid analysis of the corresponding plasma sample revealed a total of 34 alterations, including 21 targetable driver alterations. Overall, the concordance of mutation calls between routine diagnostic testing and NEOliquid was 97.6%, with a sensitivity of &gt; 70% and a specificity of 100%. Importantly, NEOliquid identified additional clinically relevant genomic alterations, not covered by routine testing. Conclusions: We have shown high concordance of genomic alterations identified from liquid biopsies and tumor tissue specimens. The excellent specificity of actionable alterations identified by NEOliquid offers analytical performance for routine diagnostic use.

Cost-effectiveness of pembrolizumab versus docetaxel for the treatment of previously treated PD-L1 positive advanced NSCLC patients in the United States

Objectives: This analysis aimed to evaluate the cost-effectiveness of pembrolizumab compared with docetaxel in patients with previously treated advanced non-squamous cell lung cancer (NSCLC) with PD-L1 positive tumors (total proportion score [TPS] ≥ 50%). The analysis was conducted from a US third-party payer perspective.Methods: A partitioned-survival model was developed using data from patients from the KEYNOTE 010 clinical trial. The model used Kaplan-Meier (KM) estimates of progression-free survival (PFS) and overall survival (OS) from the trial for patients treated with either pembrolizumab 2 mg/kg or docetaxel 75 mg/m2 with extrapolation based on fitted parametric functions and long-term registry data. Quality-adjusted life years (QALYs) were derived based on EQ-5D data from KEYNOTE 010 using a time to death approach. Costs of drug acquisition/administration, adverse event management, and clinical management of advanced NSCLC were included in the model. The base-case analysis used a time horizon of 20 years. Costs and health outcomes were discounted at a rate of 3% per year. A series of one-way and probabilistic sensitivity analyses were performed to test the robustness of the results.Results: Base case results project for PD-L1 positive (TPS ≥50%) patients treated with pembrolizumab a mean survival of 2.25 years. For docetaxel, a mean survival time of 1.07 years was estimated. Expected QALYs were 1.71 and 0.76 for pembrolizumab and docetaxel, respectively. The incremental cost per QALY gained with pembrolizumab vs docetaxel is $168,619/QALY, which is cost-effective in the US using a threshold of 3-times GDP per capita. Sensitivity analyses showed the results to be robust over plausible values of the majority of inputs. Results were most sensitive to extrapolation of overall survival.Conclusions: Pembrolizumab improves survival, increases QALYs, and can be considered as a cost-effective option compared to docetaxel in PD-L1 positive (TPS ≥50%) pre-treated advanced NSCLC patients in the US.

Predictive factors for a long-term response duration in non-squamous cell lung cancer patients treated with pemetrexed.

BackgroundPemetrexed is widely used for the treatment of advanced non-squamous non-small-cell lung cancer (NSCLC). However, factors that can predict the benefits of pemetrexed therapy have not yet been defined.MethodsWe compared the clinical and molecule pathological characteristics of good and poor responders among a cohort of 1,848 non-squamous NSCLC patients who had received at least two cycles of pemetrexed therapy between November 2006 and February 2015. Among these cases, 92 good responders who were the top 5 % in terms of progression-free survival (PFS) and 222 poor responders who had progressive disease after only 2 cycles of therapy were selected for the analysis.ResultsThe median PFS of the good responders was 29.9 months (range; 20.9–90.0) and the median number of cycle was 37 (range; 18–129). Although 53.5 % of patients showed stable disease (SD), this response was sustained (median PFS in SD, 29.6 months). A never-smoking status was related to better survival outcome, whereas EGFR mutation, two or more metastatic sites, and intra-abdominal metastasis were each associated with a poor PFS. ALK translocation showed a tendency for a positive impact on response to pemetrexed, whereas metastatic lesion to liver, adrenal gland or bone showed a tendency for a negative impact despite not reaching our threshold for statistical significance.ConclusionsPredictive factors, such as smoking status, the status of genetic alteration and tumor burden, should be considered when administering pemetrexed therapy for non-squamous NSCLC.