Management Of Advanced NSCLC Research Articles

The significance of inflammatory markers in prognosticating the effectiveness and safety of immunotherapy in conjunction with chemotherapy during the primary intervention of advanced non-small cell lung carcinoma

ObjectiveThe aim of this study is to scrutinize the prognostic significance of inflammatory biomarkers concerning the effectiveness and safety of combining PD-1 inhibition with chemotherapy in the management of advanced NSCLC. MethodsWe conducted a retrospective analysis involving 206 NSCLC patients who received treatment at Qingdao Municipal Hospital. The study encompassed the acquisition of baseline clinical attributes and hematological parameters of these patients. The optimal threshold values for PLT and NLR were ascertained based on pre-treatment evaluations, with a particular focus on their association with PFS. Variables linked to PFS were subject to scrutiny through Kaplan-Meier analysis and logistic regression. The Receiver Operating Characteristic (ROC) curve served as the means to determine the ideal cut-off values for categorizing levels of inflammatory markers into high and low classifications. We employed Chi-square tests to evaluate the relationship between elevated and reduced baseline levels of inflammatory markers and irAE. ResultsKaplan-Meier analysis disclosed that patients in the low baseline PLT group and the low NLR group exhibited a substantially more favorable prognosis in contrast to their counterparts in the high baseline PLT and high NLR groups. Multivariate analysis indicated that diminished baseline PLT and NLR levels before treatment independently foretell extended PFS. Chi-square analysis underscored a substantial correlation between baseline WBC, NEUT, LYMPH, MONO, and NLR levels and irAE. ConclusionSubdued baseline PLT and NLR levels may serve as indicators of a more auspicious prognosis in patients contending with advanced NSCLC undergoing the combination of PD-1 inhibition and chemotherapy. Elevated baseline levels of inflammatory markers antedating PD-1 therapy in advanced NSCLC may be intimately interrelated with the occurrence of irAE.

Circulating Tumour DNA (ctDNA) as a Predictor of Clinical Outcome in Non-Small Cell Lung Cancer Undergoing Targeted Therapies: A Systematic Review and Meta-Analysis.

Liquid biopsy (LB) analysis using (ctDNA)/cell-free DNA (cfDNA) is an emerging alternative to tissue profiling in (NSCLC). LB is used to guide treatment decisions, detect resistance mechanisms, and predicts responses, and, therefore, outcomes. This systematic review and meta-analysis evaluated the impact of LB quantification on clinical outcomes in molecularly altered advanced NSCLC undergoing targeted therapies. We searched Embase, MEDLINE, PubMed, and Cochrane Database, between 1 January 2020 and 31 August 2022. The primary outcome was progression-free survival (PFS). Secondary outcomes included overall survival (OS), objective response rate (ORR), sensitivity, and specificity. Age stratification was performed based on the mean age of the individual study population. The quality of studies was assessed using the Newcastle-Ottawa Scale (NOS). A total of 27 studies (3419 patients) were included in the analysis. Association of baseline ctDNA with PFS was reported in 11 studies (1359 patients), while that of dynamic changes with PFS was reported in 16 studies (1659 patients). Baseline ctDNA-negative patients had a trend towards improved PFS (pooled hazard ratio [pHR] = 1.35; 95%CI: 0.83-1.87; p < 0.001; I2 = 96%) than ctDNA-positive patients. Early reduction/clearance of ctDNA levels after treatment was related to improved PFS (pHR = 2.71; 95%CI: 1.85-3.65; I2 = 89.4%) compared to those with no reduction/persistence in ctDNA levels. The sensitivity analysis based on study quality (NOS) demonstrated improved PFS only for good [pHR = 1.95; 95%CI: 1.52-2.38] and fair [pHR = 1.99; 95%CI: 1.09-2.89] quality studies, but not for poor quality studies. There was, however, a high level of heterogeneity (I2 = 89.4%) along with significant publication bias in our analysis. This large systematic review, despite heterogeneity, found that baseline negative ctDNA levels and early reduction in ctDNA following treatment could be strong prognostic markers for PFS and OS in patients undergoing targeted therapies for advanced NSCLC. Future randomised clinical trials should incorporate serial ctDNA monitoring to further establish the clinical utility in advanced NSCLC management.

Plasma Genotyping at the Time of Diagnostic Tissue Biopsy Decreases Time-to-Treatment in Patients With Advanced NSCLC—Results From a Prospective Pilot Study

IntroductionThe availability of targeted therapies has transformed the management of advanced NSCLC; however, most patients do not undergo guideline-recommended tumor genotyping. The impact of plasma-based next-generation sequencing (NGS) performed simultaneously with diagnostic biopsy in suspected advanced NSCLC has largely been unexplored. MethodsWe performed a prospective cohort study of patients with suspected advanced lung cancer on the basis of cross-sectional imaging results. Blood from the time of biopsy was sequenced using a commercially available 74-gene panel. The primary outcome measure was time to first-line systemic treatment compared with a retrospective cohort of consecutive patients with advanced NSCLC with reflex tissue NGS. ResultsWe analyzed the NGS results from 110 patients with newly diagnosed advanced NSCLC: cohorts 1 and 2 included 55 patients each and were well balanced regarding baseline demographics. In cohort 1, plasma NGS identified therapeutically informative driver mutations in 32 patients (58%) (13 KRAS [five KRAS G12C], 13 EGFR, two ERRB2, two MET, one BRAF, one RET). The NGS results were available before the first oncology visit in 85% of cohort 1 versus 9% in cohort 2 (p < 0.0001), with more cohort 1 patients receiving a guideline-concordant treatment recommendation at this visit (74% versus 46%, p = 0.005). Time-to-treatment was significantly shorter in cohort 1 compared with cohort 2 (12 versus 20 d, p = 0.003), with a shorter time-to-treatment in patients with specific driver mutations (10 versus 19 d, p = 0.001). ConclusionsPlasma-based NGS performed at the time of diagnostic biopsy in patients with suspected advanced NSCLC is associated with decreased time-to-treatment compared with usual care.

Challenges in the management of advanced NSCLC among Italian oncologists: a 2019 national survey unfolds regional disparities.

Molecular testing is crucial for the implementation of personalized therapy in patients with lung cancer. Whether routine biomarker testing and access to personalized therapies are limited in some Italian regions is unclear. We conducted a national cross-sectional survey between April and June 2019 among Italian oncologists to determine differences in biomarker testing and access to personalized therapies for lung cancer. Based on GIMBE report n. 3/2018, 32 respondents (37.6%) were defined as belonging to budget deficit regions (BDRs) while 53 (62.4%) were from balanced/positive budget regions (BPRs). Diagnostic assays for EGFR/ALK/ROS1 and PD-L1 were reported to be available in 47/53 (88.7%) and 22/32 (68.85%) centers from BPRs and BDRs, respectively (p=0.04).Liquid biopsy accessibility was wider in BPRs than in BDRs (75.5% (40/53) vs. 50% (16/32), respectively; p=0.03). 84/85 (98.8%) oncologists reported that ⩾75% of eligible patients received first-line targeted therapies. Reason for not administering first-line targeted therapies was defined as clinically-unrelated (molecular testing not available or incomplete, pharmacoeconomic issues) by 25/42 (59.5%) of respondents from BPRs and 21/26 (80.6%) from BDRs (p=0.12). Reason for not administering first-line pembrolizumab was defined as clinically-unrelated by 8/43 (18.6%) of respondents from BPRs and 10/22 (45.4%) from BDRs (p=0.039). Disparities in access to diagnostic assay and first line immunotherapy exist between BPRs and BDRs.

What if Bevacizumab was discontinued! Can IMpower130 be exchanged for IMpower150 for advanced non-squamous NSCLC patients with PD-L1 &lt;50% and without genomic mutations?

There was a radical change in the first-line management of advanced NSCLC with negative genetic oncological drive in the last 5 years. Immune checkpoint inhibition is currently recommended for such a group of patients by major international guidelines devoted to lung cancer, as long as there is no contraindication. The recommendations came as a single agent of immune checkpoint inhibitor, combination of an immune checkpoint inhibitor with chemotherapy with an optional anti-angiogenic agent, or combination between two different immune checkpoint inhibitors; based on the level of expression of programmed death-ligand 1 in the tumour microenvironment and the type of immune checkpoint inhibitor is intended to be used. IMpower150 was a clinical trial that illustrated the effectiveness of the addition of Atezolizumab (immune checkpoint inhibitor) to chemotherapy and Bevacizumab (anti-angiogenic agent) in treatment naïve advanced non-squamous NSCLC patients with no genetic aberrations. In the same trial, there was no significant difference between chemotherapy plus either Atezolizumab or Bevacizumab. Moreover, Atezolizumab experienced other disappointing results in different clinical trials in NSCLC and other malignancies such as triple-negative breast cancer when combined with chemotherapeutic agents that require corticosteroids as pre-medications during therapy. This review evaluates the synergistic anti-neoplastic effect of immune checkpoint inhibitor and anti-angiogenic agent in NSCLC which presented in IMpower150 by Atezolizumab and Bevacizumab, especially this combination is the preferred option for other malignancies such as hepatocellular carcinoma and renal cell carcinoma. Additionally, the review overlooks the impact of corticosteroids on Atezolizumab in different clinical trials, particularly in NSCLC.

Pembrolizumab+chemotherapy versus atezolizumab+chemotherapy+/−bevacizumab for the first-line treatment of non-squamous NSCLC: A matching-adjusted indirect comparison

ObjectivesMultiple immunotherapy and chemotherapy combinations are approved for the management of advanced NSCLC which have not been directly compared in randomized clinical trials. This study indirectly compared the effectiveness of pembrolizumab + chemotherapy versus atezolizumab + chemotherapy+/-bevacizumab for previously untreated non-squamous NSCLC patients without EGFR/ALK aberrations. Materials and methodsA matching-adjusted indirect comparison (MAIC) was conducted using individual patient data (IPD) from KEYNOTE-021 Cohort G (KN021 G) (pembrolizumab + carboplatin + pemetrexed; N = 59) and KEYNOTE-189 (KN189) (pembrolizumab + pemetrexed + platinum chemotherapy; N = 410) and published aggregate data from IMpower 130 (atezolizumab + carboplatin + nab-paclitaxel; N = 451) and IMpower 150 (atezolizumab + carboplatin + paclitaxel + bevacizumab; N = 356). To adjust for cross-trial differences in baseline characteristics, data from patients randomized to pembrolizumab + chemotherapy in KN021 G/KN189 were reweighted to match the baseline characteristics of patients randomized to atezolizumab + chemotherapy from IMpower 130 or atezolizumab + chemotherapy + bevacizumab from IMpower 150. Outcomes included overall survival (OS), blinded independent review-assessed progression-free survival (PFS) and objective response rate (ORR). OS and PFS follow-up were truncated to the trial with shorter follow-up. Sensitivity analyses were conducted without truncation of follow-up of OS and PFS. ResultsAfter matching for cross-trial differences, the effective sample size of pembrolizumab + chemotherapy was 428 and 389 for the IMpower 130 and IMpower 150 comparisons, respectively. The estimated HRs (95 % CIs) of pembrolizumab + chemotherapy versus atezolizumab + chemotherapy were 0.80 (0.67,0.95) and 0.79 (0.67,0.93) with regard to OS and PFS, respectively. For pembrolizumab + chemotherapy versus atezolizumab + chemotherapy + bevacizumab, the estimated HR (95 % CIs) was 0.86 (0.72,1.03) for OS and 0.81 (0.68,0.96) for PFS. For ORR, the estimated risk ratio (95 % CI) and the risk difference (95 % CI) was 0.9 (0.8,1.1) and -3.5 % (-10.0,3.1) for pembrolizumab + chemotherapy versus atezolizumab + chemotherapy, respectively, and 0.8 (0.7,0.9) and -12.2 % (-19.6,-4.8) for pembrolizumab + chemotherapy versus atezolizumab + chemotherapy + bevacizumab, respectively. Findings were consistent across sensitivity analyses for both outcomes. ConclusionMAIC results showed a significantly better OS and PFS for pembrolizumab + chemotherapy compared with atezolizumab + chemotherapy and a significantly better PFS for pembrolizumab + chemotherapy compared with atezolizumab + chemotherapy + bevacizumab.

Epidemiologic Features of NSCLC Gene Alterations in Hispanic Patients from Puerto Rico.

Simple SummaryWe have analyzed the molecular genetic profiles of Hispanic non-small cell lung cancer (NSCLC) patients from Puerto Rico. In addition to the general characteristics, especially on EGFR mutations, we have also reported some novel findings on the incidences of KRAS mutation subgroups, other driver gene alterations, and passenger gene alterations, as well as KRAS/TP53 and KRAS/STK11 co-mutations. Moreover, our study has identified the FGFR2-TACC2 translocation in this population.Targeted therapy has changed the paradigm of advanced NSCLC management by improving the survival rate of patients carrying actionable gene alterations using specific inhibitors. The epidemiologic features of these alterations vary among races. Understanding the racial differences benefits drug development, clinical trial design, and health resource allocation. Compared to Caucasian and Asian populations, current knowledge on Hispanic patients is less and no data of Hispanic patients from Puerto Rico have been reported. We retrieved and analyzed the demographic, clinical, and molecular data of Hispanic NSCLC patients from Puerto Rico with molecular tests performed in the Genoptix Medical Laboratory in Carlsbad, CA, USA between 2011 and 2018. The majority of the NSCLC patients in our study had either adenocarcinoma (75.4%) or squamous cell carcinoma (15.1%). The incidence of EGFR mutations was 24%. They were more common in female and younger patients (<60 years). The deletion of Exon 19 and Exon 21 L858R comprised 55.1% and 31.0% of all EGFR mutations, respectively. The frequency of the T790M mutation was lower compared to that of Hispanic patients reported in the literature (0.5% vs. 2.1%). In addition, 18.7% of the patients were positive for KRAS mutations, which was at the high end of that reported in Hispanic patients. Other driver gene alterations, ALK, MET, RET, ROS1, KRAS, ERBB2, etc., demonstrated similar incidences, as well as gender and age distributions to those previously reported. The KRAS/TP53 and KRAS/STK11 co-mutations were of very low frequencies (3.6%), which could potentially affect the responsiveness to PD1/PD-L1 immunotherapy. Our study demonstrated that the prevalence of NSCLC gene alterations in Hispanic patients from Puerto Rico was comparable to the reported average prevalence in Latin American countries, supporting the intermediate NSCLC gene alteration rate of Hispanic patients between Asian and Caucasian patients. Novel information of the frequencies of KRAS mutation subtypes, driver gene alterations in ROS1, BRAF, and ERBB2, and passenger gene alterations including a rare case with the FGFR2-TACC2 translocation in Hispanic NSCLC patients from Puerto Rico were also described.

Assessment of the psychosocial and economic impact according to sex in non-small cell lung cancer patients: an exploratory longitudinal study

BackgroundLittle is known about the impact of sex on lung cancer patients from the psychological, economic and social perspectives. This study was designed to explore the psychosocial and economic impact according to sex of metastatic non-small cell lung cancer (mNSCLC) in patients and caregivers.MethodsExploratory study of two cohorts of patients starting first-line treatment for mNSCLC. The following questionnaires were administered at baseline, 4 months later and following the first and second disease progression: APGAR, relationship impact scale, DUKE-UNC scale, economic impact in patients and caregiver, and Zarit scale. It was planned to include 1250 patients to get an 80% possibility of detecting as significant (p < 0.05) effect sizes less than 0.19 between men and women. Univariate comparisons were made between the tests applied to men and women. Overall survival was estimated with Kaplan–Meier method. Cox analyses were done to estimate hazard ratios (HRs) with 95% CI.Results333 patients were included. Most families reported to continue being functional despite the lung cancer diagnosis. Regardless of sex, they did not perceive changes in their partner relationship. Most patients felt their social support was normal. Roughly 25% of people reported a worsening in their economic situation, without remarkable differences by sex. Statistically significant differences were found between both groups regarding the caregiver’s relationship to the patient (more parents were the caregiver in females than in males, p < 0.0001) and the caregiver’s employment situation (more employed caregivers in females) (p < 0.0001). Most caregivers of both sexes considered that taking care of their relative did not pose a significant burden.ConclusionsThis study provides a preliminary insight into sex-related characteristics in the management of advanced NSCLC and its impact on the emotional, social and economic burden of patients and their caregivers, and recall the high priority of researching in cancer from a sex perspective. Nevertheless, due to the low recruitment rate and the relevant loss of patients during the follow-up, it was difficult to find differences by sex.Trial registrationClinicalTrials.gov identifier: NCT02336061.Ethics committeeComité Ético de Investigación Clínica del Hospital Clínic de Barcelona, Spain. Reference number: HCB/2014/0705.

Immunotherapy in EGFR-Mutant and ALK-Positive Lung Cancer: Implications for Oncogene-Driven Lung Cancer.

Non-small cell lung cancer (NSCLC) is a heterogeneous disease, commonly defined by genetic alterations in oncogenic drivers. Targeted therapies have transformed the management of oncogene-driven lung cancers, with targeted agents now approved in the United States for 7 distinct molecular alterations. Nonetheless, acquired resistance remains an ongoing challenge, underscoring the need for alternative therapeutic approaches. Immune checkpoint inhibitors targeting the programmed cell death 1 (PD-1) axis have emerged as important therapies in the management of advanced NSCLC, but the role of these agents in patients with oncogenic driver mutations remains unclear. Here, we focus on epidermal growth factor receptor-mutant and anaplastic lymphoma kinase-rearranged NSCLC as paradigms to explore the role of immune checkpoint inhibitors in oncogene-driven NSCLC. We provide an overview of the clinical data examining programmed death ligand 1 (PD-L1) inhibitor monotherapy, PD-(L)1 inhibitors, and tyrosine kinase inhibitor combinations, as well as combinations of PD-(L)1 inhibitors and chemotherapy.

PD01.02 Oncologists’ Management of Advanced NSCLC: a Simulation-Based Performance Assessment

PD01.02 Oncologists’ Management of Advanced NSCLC: a Simulation-Based Performance Assessment

PC07.01 Debate 1: Chemotherapy Will Become a Thing of the past in the Management of Advanced NSCLC - For

PC07.01 Debate 1: Chemotherapy Will Become a Thing of the past in the Management of Advanced NSCLC - For

ISY10-1 - Future perspectives of precision medicine for NSCLC

Over the past decade, significant advances have been made in the management of advanced NSCLC. The dramatic development of individualized therapies have propelled this malignance to the forefront of precision medicine. Nowadays, NSCLC has been divided into several distinct subtypes based on molecular alterations, including EGFR mutations, ALK/ROS1/NTRK translocations, and BRAFV600E mutations et al. Targeted therapy inhibiting specific actionable driver genes has resulting in a significant improvement in response rate and disease control. Targeted therapies for rare oncogenic drivers, including EGFR 20 insertions, HER2 exon 20 mutations, RET fusions, etc., are also under clinical development currently. Notably, due to low frequency of uncommon driver genes, classical randomized-controlled trial may not be the optimal approaches. Innovative biomarker-driven trials, such as Umbrella and Basket trials, may help screening patients effectively and evaluating multiple targeted drugs in matched patients. On the other hand, immune checkpoint blockades (ICBs) by inhibiting the programmed death protein 1/programmed death ligand 1 axis has yielded promising clinical responses in patients with advanced NSCLC, especially for those without EGFR/ALK aberrations. However, the response rate to ICBs is low (about 20%), mainly due to the dynamic expression of PD-L1 on tumor cells or immune cells, degree of mutational/neoantigen load, intratumoral heterogeneity, infiltrated immune cells of tumor microenvironment of NSCLC. Unlike targeted therapy, most single-gene biomarkers are not accurate for predicting ICBs efficacy and multi-omics and holistic approaches are needed. ICBs in combinations with chemotherapy, radiation therapy, or novel immunomodulatory agents are also currently being evaluated. However, the optimal order or duration of these drugs also needs further investigation. Nevertheless, there is still a lot of work to do before the era of precision medicine is truly coming.

Treatment of Complications from Immune Checkpoint Inhibition in Patients with Lung Cancer.

Opinion statementImmune checkpoint inhibitors have revolutionized the management of advanced NSCLC. With the intention of generating an anti-tumor immune response, ICIs can also lead to inflammatory side effects involving a wide variety of organs in the body, termed immune-related adverse events. Although no prospective clinical trial exists to guide recommendations for optimal and more specific immunosuppressive treatments rather than corticosteroids, further studies may lead to a more mechanistic-based approach towards these toxicities in the future. In relation to current practice, we recommend adherence to the recent published guidelines which emphasize the importance of early recognition and administration of temporary immunosuppressive therapy with corticosteroids in most cases, depending on the organ system involved, and the severity of toxicity. Recognition of these toxicities is increasingly important as the use of these agents expand within different indications for patients with lung cancers, and to other tumor types.

P2.07-036 Appropriate Use of Immune Checkpoint Inhibitors in Advanced NSCLC: Effectiveness of Unique Case-Based Education on Clinical Decision-Making

The past several years have witnessed unparalleled changes in treatment for patients with advanced NSCLC. Although these changes present significant hope, it remains unclear if oncologists have been able to stay current on the breadth of practice changes, and effectively incorporate evidence-base into practice. The objective of this study was to evaluate oncologists’ competence regarding the use of immune checkpoint inhibitors (ICI) in the management of advanced NSCLC and the impact of education on narrowing gaps in clinical practices.

Baseline and On-Treatment Characteristics of Serum Tumor Markers in Stage IV Oncogene-Addicted Adenocarcinoma of the Lung.

The role of serum tumor markers in the modern management of advanced NSCLC remains poorly described. A single-center retrospective analysis of available carcinoembryonic antigen, CA125, CA19.9, and CA27.29 levels at baseline and during treatment of stage IV lung adenocarcinoma by oncogenic driver was conducted. A total of 142 patients were analyzed (60 with anaplastic lymphoma kinase gene [ALK] rearrangement, 50 with EGFR mutation, four with ROS1 rearrangement, and 29 with KRAS mutation). Of these, 82% had at least one marker (95% if all four markers were measured), with CA27.29 being the most commonly increased and CA19.9 the rarest. Only CA27.29 differed significantly by oncogene (it was less common in KRAS) (p= 0.016). The median times to nadir during tyrosine kinase inhibitor (TKI) therapy in EGFR and ALK cases were 16.4 and 20 weeks, respectively. Of the 41 patients with EGFR mutation or ALK or ROS1 rearrangement, 24 (59%) demonstrated an initial increase within the first 4 weeks of TKI therapy, 58% of whom then had their levels fall below baseline. An increase in marker level of 10% or more from nadir occurred in 53% of systemic and 22% of central nervous system-only progression. Serum tumor markers are frequently increased in lung adenocarcinoma regardless of driver oncogene. Changes within the first 4 weeks of therapy may be misleading. Progression is associated with marker increases, especially in sites other than the central nervous system.

Monitoring response of PDL-1 directed immunotherapy in patients with advanced NSCLC using serum CEA levels.

e20509 Background: Immunotherapy (IT) response measurements in advanced NSCLC management are evolving. We describe here our retrospective single institutional experience in measuring serum CEA levels as an early response determinant and correlation with radiographic assesment. Methods: Retrospective chart review was performed after obtaining IRB approval. Demographic information, stage, histology, prior treatment, IT agent used, radiographic response assesment and serum CEA levels were recorded. Patients were evaluable if they had elevated baseline serum CEA levels (normal range non smokers: 0-3 ng/ml, smokers 0-5 ng/ml), had recieved at least two cycles of IT and had radiographic response assessment performed. Results: Six eligible patients were identified. Median age 60 yrs; M:F1:5, SCC n=1, Adeno: n=5; Smoking history positive n=4; Stage IV n=6, EGFR mut+ n=2; IT agent used: nivolumab: n=5; atezolizumab: n=1. IT as 1st line of Rx n=1; 2nd line n=3, 3rd line: n=2. On first radiographic assesment: three patients had progressive disease (PD), Two patients had PR, one patient (#1) had an intial PR and subsequently PD with subsequent rise in CEA level to 16.1 corelating with PD on radiographs. Conclusions: Serum CEA levels appear to correlate well with response assesment in patients with advanced NSCLC while being treated with immunotherapy. This small study is hypothesis generating and is currently being evaluated in a larger series. [Table: see text]

Defining the Issues in the Treatment of Elderly Patients With Advanced Non-Small-Cell Lung Cancer

SUMMARY Elderly patients constitute a substantial proportion of patients with advanced NSCLC. Several unresolved issues surround the treatment of elderly patients with NSCLC, including under-representation in clinical trials, the definitions of fit and unfit patients and the appropriate age cut-off for this population. Taken together, these factors have a large impact on the treatment of elderly patients with advanced NSCLC. An urgent need exists to develop new strategies for clinical trial design that may lead to improved outcomes in these patients. This review will address the existing barriers and controversies in the management of advanced NSCLC in the elderly, focusing on cytotoxic chemotherapy regimens. Results of clinical trials conducted in the elderly and those from planned subset analyses for age-unspecified trials will be provided, with a focus on recently reported studies. Outcomes from population databases reporting on this population in a nonclinical trial setting will be reviewed.

Quality of Life Analysis of Esogia-Gfpc-Gecp Trial- a Phase Iii, Randomized, Multicenter Study Comparing in Elderly Patients (≥70 Years) with Stage Iv Nsclc a Treatment Allocation Based on Ps and Age with an Experimental Strategy According to a Comprehensive Geriatric Assessment (Cga)

ABSTRACT Aim: The use of a CGA is recommended to detect a patient's vulnerability but its integration in treatment decision making has never been prospectively evaluated. Our main objective was to test if the use of CGA in the allocation of treatment could improve the management of advanced NSCLC in first line. Methods: Randomized, multicentric, prospective phase III study in patients ≥70 y, PS 0-2 with stage IV NSCLC. Arm A standard algorithm of chemotherapy allocation: carboplatin based doublet in PS ≤ 1 and age ≤75y, docetaxel in PS =2 or age >75y. Arm B treatment allocation based on CGA: carboplatin based doublet for fit patients, mono-therapy for vulnerable patients and BSC for frail patients. Four cycles were given every three weeks. Main endpoint: time to failure free survival (TFFS) Secondary endpoints: overall Response Rate (ORR), overall survival (OS), toxicity, QoL and life expectancy adjusted on QoL. QoL was assessed during treatment by EQ-5D health questionnaire at baseline, weeks 6, 12, 20, 28, and 36. A mixed-effects model was used, to compare the utility score and therefore the QOL between arms A and B. Results: 493 patients were randomized from 01/2010 to 01/2013 by 45 centers. Respectively in arms A and B, 34.4% and 47% of patients received a carboplatin-based doublet, 65.6% and 31.4% received docetaxel and in arm B 21.5% received BSC. Median TFFS was 3.2 m, 95%CI:[2.9; 4.1] for standard arm and 3.1 m, 95%CI:[2.7; 4.4] for experimental arm, p = 0.71. Compliance with QoL was 87% at baseline and respectively 66%, 65%, 54%, 60% and 57% at week 6, 12, 20, 28 and 36. The utility score at each evaluation is superior in the experimental arm than in the standard arm, but this difference is significant only at week 36 (p = 0.02). Using a linear mixed generalized model, the utility score tends to decrease over time and is not significantly different between the two arms (p = 0.85). Life expectancy adjusted on QoL was 130.1 days in standard arm and 133.3 days in experimental arm, p = 0.51. Conclusions: ESOGIA did not show a superiority of a CGA-based treatment allocation. In the experimental arm, more patients received a carboplatin-based doublet and 21% of frail patients received an exclusive BSC management. Despite a trend in favor of CGA arm, there is no significant difference in terms of QoL score and life expectancy adjusted on QoL. Further sudies are needed for GA in NSCLC elderly patients. Disclosure: C. Chouaid: advisory board LILLY; H. Lena: advisory board Lilly. All other authors have declared no conflicts of interest.

Analysis of regulatory T cells in patients of NSCLC with malignant pleural effusion.

e17511 Background: Enrichment of regulatory T (Treg) cells at the affected anatomic site in cancer may suppress the anti-tumor immune response influencing the cancer progression. Understanding of the clinical relevance of Treg mediated suppression of anti-tumor immune response and mechanisms underlying their preferential trafficking to the affected anatomic site is still limited. The aim of this study was to enumerate the frequencies of Treg cells in malignant pleural effusion and peripheral blood of patients with advanced NSCLC and it’s trend after treatment. Methods: Treg frequencies were evaluated in pleural effusion and peripheral blood of the patients with advanced NSCLC (n=27) using flowcytometry and compared with peripheral blood of age and sex matched healthy controls (n=15) and tubercular pleural effusions (n=10). The Treg cells were characterized as CD4+CD25+Foxp3+ T cells gated on CD4+CD25+ T cells. We assessed the effect of treatment response on Treg frequency. We have also looked for the expression of chemokine receptors CCR4 and CCR6 on the Tregs in pleural effusion and peripheral blood of the patients. Results: Compared to healthy controls, frequency of CD4+CD25+Foxp3+ Tregs was significantly increased in peripheral blood of patients with NSCLC (p=0.0036). In pleural effusion of patients, Treg frequency was higher than their corresponding peripheral blood (p=0.025). As compared to tubercular pleural effusion Treg frequency was higher in malignant effusion (p&lt;0.0001). We had 12 patients who completed treatment and in whom response evaluation was available. Treg frequency reduced at the time of response (PR or SD) and increased again at disease progression. Surface expression of CCR4 and CCR6 was higher on Treg cells as compared to non Treg CD4 cells among the patients (p=0.0001; p=0.001 respectively). However, there was no difference in expression of these chemokine receptors on Tregs in pleural fluid and peripheral blood. Conclusions: Tregs are increased in patients of NSCLC, both at disease site and in systemic circulation. This increase may be chemokine receptors mediated. Treg frequency changes with treatment and response. Modulation of Tregs may have therapeutic implication in the management of advanced NSCLC.

US Guidelines for Management of Advanced NSCLC

US Guidelines for Management of Advanced NSCLC