Evaluation of Omics-Based Strategies for the Management of Advanced Lung Cancer

PURPOSE: Omic-informed therapy is being used more frequently for patients with non–small-cell lung cancer (NSCLC) being treated on the basis of evidence-based decision-making. However, there is a lack of a standardized framework to evaluate those decisions and understand the association between omics-based management strategies and survival among patients. Therefore, we compared outcomes between patients with lung adenocarcinoma who received omics-driven targeted therapy versus patients who received standard therapeutic options. PATIENTS AND METHODS: This was a retrospective study of patients with advanced NSCLC adenocarcinoma (N = 798) at City of Hope who received genomic sequencing at the behest of their treating oncologists. A thoracic oncology registry was used as a clinicogenomic database to track patient outcomes. RESULTS: Of 798 individuals with advanced NSCLC (median age, 65 years [range, 22-99 years]; 60% white; 50% with a history of smoking), 662 patients (83%) had molecular testing and 439 (55%) received targeted therapy on the basis of the omic-data. A fast-and-frugal decision tree (FFT) model was developed to evaluate the impact of omics-based strategy on decision-making, progression-free survival (PFS), and overall survival (OS). We calculated that the overall positive predictive value of the entire FFT strategy for predicting decisions regarding the use of tyrosine kinase inhibitor–based targeted therapy was 88% and the negative predictive value was 96%. In an adjusted Cox regression analysis, there was a significant correlation with survival benefit with the FFT omics-driven therapeutic strategy for both PFS (hazard ratio [HR], 0.56; 95% CI, 0.42 to 0.74; P < .001) and OS (HR, 0.51; 95% CI, 0.36 to 0.71; P < .001) as compared with standard therapeutic options. CONCLUSION: Among patients with advanced NSCLC who received care in the academic oncology setting, omics-driven therapy decisions directly informed treatment in patients and was correlated with better OS and PFS.

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Impact of COPD treatment on survival in patients with advanced non-small cell lung cancer

10.21203/rs.3.rs-741440/v1 ◽

2021 ◽

Author(s):

Hyunji Jo ◽

Sojung Park ◽

Nam Eun Kim ◽

So Young Park ◽

Yon Ju Ryu ◽

...

Keyword(s):

Lung Cancer ◽

Treatment Group ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Advanced Nsclc ◽

Small Cell ◽

Newly Diagnosed ◽

Small Cell Lung ◽

Cox Regression Analysis ◽

The Impact

Abstract Background Chronic obstructive pulmonary disease (COPD) is associated with a poor prognosis in patients with non-small cell lung cancer (NSCLC). However, the impact of COPD treatment on the survival of patients with advanced NSCLC remains uncertain. Methods We retrospectively investigated COPD patients among patients newly diagnosed with advanced NSCLC between September 2005 and August 2019 at a university hospital. The diagnosis of COPD was made by forced expiratory volume in 1 second (FEV1)/forced vital capacity < 0.7 with spirometry performed within one year before and after the diagnosis of NSCLC. The clinical characteristics, lung function, and survival outcomes were analyzed and compared between patients who did and did not receive COPD treatment. Results Among 221 patients with advanced NSCLC and COPD, 124 received treatment for COPD and 97 did not receive treatment for COPD. A total of 190 (86.0%) patients were newly diagnosed with COPD at the time of diagnosis of advanced NSCLC. FEV1 and FEV1 % predicted values were greater in the no-treatment group than in the COPD treatment group (P < 0.001). The median overall survival (OS) of the treatment group was 10.7 months while that of the no-treatment group was 8.7 months (P = 0.007). In multivariate Cox regression analysis, COPD treatment was independently associated with improved OS after adjustment for sex, age, body mass index, FEV1, lung cancer stage, and chemotherapy (hazard ratio, 0.71; 95% confidence interval, 0.53–0.95; P = 0.021). Conclusion COPD treatment was associated with improved OS in patients with advanced NSCLC and COPD. Therefore, pretreatment spirometry and maximal treatment for COPD may offer a chance of optimal management for patients with advanced NSCLC.

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Pemetrexed Versus Pemetrexed and Carboplatin As Second-Line Chemotherapy in Advanced Non–Small-Cell Lung Cancer: Results of the GOIRC 02-2006 Randomized Phase II Study and Pooled Analysis With the NVALT7 Trial

Journal of Clinical Oncology ◽

10.1200/jco.2012.43.6758 ◽

2012 ◽

Vol 30 (36) ◽

pp. 4501-4507 ◽

Cited By ~ 31

Author(s):

Andrea Ardizzoni ◽

Marcello Tiseo ◽

Luca Boni ◽

Andrew D. Vincent ◽

Rodolfo Passalacqua ◽

...

Keyword(s):

Lung Cancer ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Advanced Nsclc ◽

Pooled Analysis ◽

Small Cell ◽

Second Line ◽

Small Cell Lung ◽

Platinum Based Chemotherapy ◽

The Impact

Purpose To compare efficacy of pemetrexed versus pemetrexed plus carboplatin in pretreated patients with advanced non–small-cell lung cancer (NSCLC). Patients and Methods Patients with advanced NSCLC, in progression during or after first-line platinum-based chemotherapy, were randomly assigned to receive pemetrexed (arm A) or pemetrexed plus carboplatin (arm B). Primary end point was progression-free survival (PFS). A preplanned pooled analysis of the results of this study with those of the NVALT7 study was carried out to assess the impact of carboplatin added to pemetrexed in terms of overall survival (OS). Results From July 2007 to October 2009, 239 patients (arm A, n = 120; arm B, n = 119) were enrolled. Median PFS was 3.6 months for arm A versus 3.5 months for arm B (hazard ratio [HR], 1.05; 95% CI, 0.81 to 1.36; P = .706). No statistically significant differences in response rate, OS, or toxicity were observed. A total of 479 patients were included in the pooled analysis. OS was not improved by the addition of carboplatin to pemetrexed (HR, 90; 95% CI, 0.74 to 1.10; P = .316; P heterogeneity = .495). In the subgroup analyses, the addition of carboplatin to pemetrexed in patients with squamous tumors led to a statistically significant improvement in OS from 5.4 to 9 months (adjusted HR, 0.58; 95% CI, 0.37 to 0.91; P interaction test = .039). Conclusion Second-line treatment of advanced NSCLC with pemetrexed plus carboplatin does not improve survival outcomes as compared with single-agent pemetrexed. The benefit observed with carboplatin addition in squamous tumors may warrant further investigation.

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Higher predictive value of tumour and node [18F]-FDG PET metabolic volume and TLG in advanced lung cancer under chemotherapy

Nuclear Medicine Communications ◽

10.1097/mnm.0000000000000145 ◽

2014 ◽

Vol 35 (9) ◽

pp. 908-915 ◽

Cited By ~ 7

Author(s):

Anaïs Olivier ◽

Gregory Petyt ◽

Alexis Cortot ◽

Arnaud Scherpereel ◽

Claude Hossein-Foucher

Keyword(s):

Lung Cancer ◽

Predictive Value ◽

Fdg Pet ◽

Advanced Lung Cancer ◽

18F Fdg ◽

Metabolic Volume

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Therapeutic Options for the Treatment of Advanced Lung Cancer: Introduction

Seminars in Thoracic and Cardiovascular Surgery ◽

10.1053/j.semtcvs.2008.09.006 ◽

2008 ◽

Vol 20 (3) ◽

pp. 183 ◽

Cited By ~ 1

Author(s):

Valerie W. Rusch ◽

Christopher G. Azzoli ◽

Kenneth E. Rosenzweig

Keyword(s):

Lung Cancer ◽

Therapeutic Options ◽

Advanced Lung Cancer

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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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The predictive value of MAP2K1/2 mutations for efficiency of immunotherapy in melanoma.

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.15_suppl.e21587 ◽

2021 ◽

Vol 39 (15_suppl) ◽

pp. e21587-e21587

Author(s):

Ting Ye ◽

Jieying Zhang ◽

Xinyi Liu ◽

Mengmei Yang ◽

Yuhan Zhou ◽

...

Keyword(s):

Overall Survival ◽

Predictive Value ◽

Cox Regression ◽

Treatment Options ◽

Objective Response ◽

Progression Free Survival ◽

Driver Mutations ◽

Cox Regression Analysis ◽

Melanoma Patients ◽

The Impact

e21587 Background: Immunotherapies targeting immune checkpoint receptors have become the cornerstone of systemic treatment options for malignant melanoma. The response to these immunotherapies may correlate with driver mutations. MAP2K1/2 genes are mutated in approximately 10% of melanomas, however, the impact of MAP2K1/2 gene alterations on the efficiency of immunotherapy has not been clarified. Methods: Six metastatic melanoma clinical cohorts treated with ICIs were included to investigate the association between clinical efficacy of immunotherapy and MAP2K1/2 mutations. Survival analyses were conducted in cohorts receiving two kinds of ICB agents, namely anti-CTLA-4 or anti-PD-1. RNA expression profiling from these cohorts and from the TCGA melanoma cohort were used to explore the potential mechanism related to immune activation. Results: In an independent anti-CTLA-4-treated cohort (n = 110), we found that MAP2K1/2 mutations are predictive of high objective response rate (17.6% vs 1.3%, p = 0.0185) and long progression-free survival [median OS, 49.2 months vs 8.3 months; hazard ratio (HR) = 0.37; 95% CI, 0.15–0.91; p = 0.0307] and overall survival (median PFS, 19.4 months vs 2.8 months; HR = 0.2; 95% CI, 0.05–0.83; p = 0.0262). This predictive value was further validated in a pooled anti-CTLA-4-treated cohort (n = 235) in terms of overall survival (median OS, 49.3 months vs 22.0 months; HR = 0.44; 95% CI, 0.22–0.91; p = 0.0255). However, no correlation between MAP2K1/2 mutations and overall survival was observed in the anti-PD-1-treated cohort (n = 285). Subgroup Cox regression analysis indicated that MAP2K-mutated patients receive less benefit from the anti-PD-1 monotherapy than from the anti-CTLA-4 treatment (median OS, 27.0 months vs 49.3 months; HR = 3.26; 95% CI, 1.18–9.02; p = 0.0225), which was contrary to the result obtained for the total population. Furthermore, transcriptome profiling analysis revealed that MAP2K-mutated tumors are enriched in CD8+ T cells, B cells, and neutrophil cells and also express high levels of CD33 and IL10, which might be the underlying mechanism for melanoma patients with MAP2K1/2-mutated benefit more from anti-CTLA-4 treatment. Conclusions: We identified mutations in MAP2K1/2 genes as the independent predictive factors for anti-CTLA-4 therapy in melanoma patients and found that anti-CTLA-4 treatment in patient harbouring MAP2K1/2 mutations might be more effective than the anti-PD-1 therapy.

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Impact of Cancer Cachexia on Treatment With PD-1/PD-L1 Inhibitors Plus Chemotherapy in Advanced Non-small-Cell Lung Cancer

10.21203/rs.3.rs-524527/v1 ◽

2021 ◽

Author(s):

Taichi Miyawaki ◽

Tateaki Naito ◽

Michitoshi Yabe ◽

Hiroaki Kodama ◽

Naoya Nishioka ◽

...

Keyword(s):

Lung Cancer ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Cancer Cachexia ◽

Advanced Nsclc ◽

Group Performance ◽

Objective Response ◽

Small Cell ◽

Small Cell Lung ◽

The Impact

Abstract PurposeProgrammed cell death-1 (PD-1)/programmed death-ligand 1 (PD-L1) inhibitors plus chemotherapy has become the standard first-line treatment in patients with advanced non-small-cell lung cancer (NSCLC). However, few studies have explicitly focused on the impact of cancer cachexia on the efficacy of PD-1/PD-L1 inhibitors plus chemotherapy. Thus, we evaluated the clinical implications of cancer cachexia on the survival outcomes in patients who received this treatment.MethodsWe conducted a retrospective review of medical records of patients with advanced NSCLC treated with PD-1/PD-L1 inhibitors plus chemotherapy from December 2018 to December 2020. Cancer cachexia was diagnosed as an unintentional weight loss of 5% or more over six months. We evaluated the progression-free survival (PFS) and overall survival (OS) for patients with or without cancer cachexia who received PD-1/PD-L1 inhibitors plus chemotherapy.ResultsAmong the 80 included patients, 37 (46%) had cancer cachexia. Cachectic patients had a lower objective response rate (30 vs 51%, P <0.05), poorer PFS (2.3 vs 12.0 months, P <0.05), and poorer OS (10.8 vs 23.9 months, P <0.05) than non-cachectic patients. The Cox proportional-hazard ratios (95% confidence interval) of cancer cachexia were 1.77 (1.01–3.10) for PFS and 2.90 (1.40–6.00) for OS, with adjustments for Eastern Cooperative Oncology Group performance status, PD-L1 tumour proportion score, histology, and central nervous system metastases. ConclusionPre-treatment cancer cachexia may reduce treatment efficacy and shorten survival time in patients receiving PD-1/PD-L1 inhibitors plus chemotherapy. Early evaluation and intervention for cancer cachexia might improve oncological outcomes in patients with advanced NSCLC.

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Clinical outcomes of patients with HER2-mutant advanced lung cancer: chemotherapies versusHER2-directed therapies

Therapeutic Advances in Medical Oncology ◽

10.1177/1758835920936090 ◽

2020 ◽

Vol 12 ◽

pp. 175883592093609

Author(s):

Jiebai Zhou ◽

Ning Ding ◽

Xiaobo Xu ◽

Yong Zhang ◽

Maosong Ye ◽

...

Keyword(s):

Lung Cancer ◽

Targeted Therapy ◽

Clinical Outcomes ◽

Disease Diagnosis ◽

Advanced Lung Cancer ◽

Insertion Mutation ◽

Targeted Agents ◽

First Line ◽

Line Therapy ◽

Exon 20

Background: Lung cancer is now the leading cause of cancer mortality worldwide for both men and women. In non-small cell lung cancer (NSCLC), matching a specifically targeted drug to the identified driver mutation in each patient resulted in dramatically improved therapeutic efficacy, often in conjunction with decreased toxicity. Mutations in HER2 have been identified as an oncogenic driver gene for NSCLC. This retrospective study was conducted to better understand the clinical outcomes of advanced lung cancer patients harboring HER2 mutations treated with chemotherapies and HER2-targeted agents, as well as the optimal clinical choice. Methods: Patients who were diagnosed with advanced lung cancer (stage IIIB/IV) and had undergone molecular testing at Zhongshan Hospital, Fudan University, Shanghai, China from April 2016 to December 2018 were reviewed. For patients that had HER2 mutant advanced lung cancer, we analyzed their clinical and molecular features and clinical outcomes, including overall survival (OS), progression-free survival (PFS), disease control rate (DCR) and objective response rate (ORR). Results: We identified 44 patients harboring HER2 mutations. Their median age was 56 years, with the majority being women ( n = 24), never smokers ( n = 32), and having the adenocarcinoma genotype ( n = 42). Amongst the HER2 mutations present, a 12 base pair in-frame insertion in exon 20 with p.771insAYVM was the most common subtype in patients with known detail variants of HER2 mutation (9/27). The median OS from the date of advanced disease diagnosis was 9.9 months with 24 deaths, and a median follow-up of 12.7 months for survivors. For patients with a known HER2 exon 20 insertion mutation, OS tended to be superior (though not statistically) in the first-line HER2-TKI group to that in the group receiving chemotherapy (10.8 versus 9.8 months, p = 0.40). However, patients that received first-line chemotherapy had a median PFS of 5.9 months, numerically longer than that of the HER2-TKI group (4.6 months, p = 0.63). Patients who received HER2-targeted therapy as first-line therapy had an improved OS (10.8 versus 10.1 months, p = 0.30) and PFS (4.6 versus 2.8 months, p = 0.36) relative to those who received HER2-targeted therapy as subsequent-line therapy, although they did not meet the threshold for statistical significance. Furthermore, patients with AYVM mutation were associated with poor clinical outcomes. Conclusion: Pemetrexed-based chemotherapy remains an important component of care for patients with HER2-mutant NSCLC. HER2-TKI given as an initial therapy may bring more clinical benefits than when given as a subsequent-line therapy. Refining the patient population based on patterns of HER2 variants may help improve the efficacy of anti- HER2 treatment in lung cancer. Developing highly effective and tolerable HER2-targeted agents is urgently needed for this population.

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P1.16-07 Real World Evidence of the Impact of Immunotherapy in Patients with Advanced Lung Cancer

Journal of Thoracic Oncology ◽

10.1016/j.jtho.2019.08.1233 ◽

2019 ◽

Vol 14 (10) ◽

pp. S588

Author(s):

C. Pettengell ◽

J. Law ◽

L. Le ◽

M. Sung ◽

S. Lau ◽

...

Keyword(s):

Lung Cancer ◽

Real World ◽

Advanced Lung Cancer ◽

Real World Evidence ◽

The Impact

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The Association Between Medicare Low-Income Subsidy and Anticancer Treatment Uptake in Advanced Lung Cancer

JNCI Journal of the National Cancer Institute ◽

10.1093/jnci/djz183 ◽

2019 ◽

Vol 112 (6) ◽

pp. 637-646 ◽

Cited By ~ 3

Author(s):

Yi-Ting Chou ◽

Joel F Farley ◽

Thomas E Stinchcombe ◽

Amber E Proctor ◽

Jennifer Elston Lafata ◽

...

Keyword(s):

Lung Cancer ◽

Confidence Interval ◽

Low Income ◽

Advanced Nsclc ◽

Statistical Tests ◽

Advanced Lung Cancer ◽

Part D ◽

Treatment Uptake ◽

Anticancer Treatment ◽

Out Of Pocket Costs

Abstract Background High out-of-pocket costs may impact anticancer treatment uptake. The Low-Income Subsidy (LIS) program can reduce patient out-of-pocket cost for Medicare Part D–covered treatments. We examined whether the LIS increased uptake and reduced time to initiate orally administered anticancer drugs in patients with advanced non–small cell lung cancer (NSCLC). Methods Using Surveillance, Epidemiology and End Results (SEER)-Medicare data, we identified older adults (aged 65 years and older) diagnosed with advanced NSCLC from 2007 through 2013 and categorized them as full LIS, partial LIS, or non-LIS. We used propensity-score weighted (IPTW) Cox proportional hazards regression to assess the likelihood of and time to initiate Part D treatments. Part B medication uptake was our negative control because supplemental insurance reduces out-of-pocket costs for those drugs. All statistical tests were two-sided. Results Among 19 746 advanced NSCLC patients, approximately 10% initiated Part D treatments. Patients with partial or no LIS were less likely to initiate Part D treatments than were those with full subsidies (partial LIS vs full LIS HRIPTW = 0.77, 95% confidence interval = 0.62 to 0.97; non-LIS vs full LIS HRIPTW = 0.87, 95% confidence interval = 0.79 to 0.95). Time to initiate Part D treatments was also slightly shorter among full-LIS patients (full LIS mean [SD] = 10.8 [0.04] months; partial LIS mean [SD] = 11.3 [0.08] months; and non-LIS mean [SD] = 11.1 [0.03] months, P < .001). Conversely, patients with partial or no LIS had shorter time to initiation of Part B drugs. Conclusions Patients receiving the full LIS had higher orally administered anticancer treatment uptake than patients without LIS. Notably, patients with partial LIS had the lowest treatment uptake, likely because of their low incomes combined with high expected out-of-pocket spending. High out-of-pocket costs for Part D medications may be a barrier to treatment use for patients without full LIS.

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