Virtual Library
Start Your Search
K. Syrigos
Author of
-
+
MTE19 - Monitoring of Treatment Outcome in Clinical Trials and in Routine Practice (Ticketed Session) (ID 313)
- Event: WCLC 2016
- Type: Meet the Expert Session (Ticketed Session)
- Track: Chemotherapy/Targeted Therapy/Immunotherapy
- Presentations: 1
- Moderators:
- Coordinates: 12/06/2016, 07:30 - 08:30, Stolz 1
-
+
MTE19.02 - Monitoring of Treatment Outcome in Clinical Trials and in Routine Practice (ID 6575)
08:00 - 08:30 | Author(s): K. Syrigos
- Abstract
- Presentation
Abstract:
Monitoring of treatment efficacy and treatment-related toxicity –both in the real-world and the clinical trial setting- is a crucial, complex and constantly evolving aspect in the field of modern personalized oncology. The expansion of our lung cancer armamentarium, due to continuous implementation of novel (and costly) targeted and immunotherapeutic agents, along with their companion diagnostics, has inevitably led not only to substantial improvements in clinical outcomes, but also to increasing demands for a more accurate prediction and prevention of toxicities and more robust evaluation of cost-effectiveness. Furthermore, transition to targeted therapies displaying modes of action and biologic behavior vastly distinct to those of traditional cytotoxic agents, has necessitated the need to revisit our concept of what constitutes “tumor response” in lung cancer treatment (and solid tumors in general). Vital issues that need to be urgently -albeit concertedly- addressed include –but are not limited to- the need to adapt response evaluation criteria, monitoring tools and techniques to this rapidly changing landscape of lung cancer treatment and to increase our focus towards a patient-centered standard of care. Monitoring of treatment efficacy using imaging modalities Monitoring of tumor size changes -as evidenced on quantitative imaging modalities such as CT and MRI scans and typically assessed by the unidimensional RECIST criteria- remains the cornerstone of treatment response evaluation and decision-making in oncology practice and a strong surrogate endpoint for overall survival in clinical trials. Limitations of this approach are, nevertheless, significant and increasingly recognized. First, measurement inaccuracies and considerable inter-observer variability should be pointed out. Second, considerable time and cycles of cytotoxic drugs are needed prior to the appearance of any clinically meaningful tumor size changes on standard imaging studies, meaning that a reduction of tumor volume alone may not represent an early indicator of treatment response. Third, antitumor activity of targeted agents, which may not necessarily result in significant tumor size modification, cannot be accurately assessed or predicted with the use of these conventional strategies; multiparametric imaging –evaluating both anatomical and functional parameters of tumors-is thus required for optimal assessment of tumor behavior (stability, progression or regression). Within this context, functional imaging modalities (i.e. dynamic contrast-enhanced MRI, diffusion weighted imaging or FDG-PET and FLT-PET ) with the potential to visualize physiologic changes in the molecular level, have been investigated for their ability to influence decision-making by predicting or monitoring response to molecularly targeted agents or their value as surrogate outcome measures in the trial setting. Notably, FDG-PET is increasingly used for the evaluation of treatment response (mainly with PET response criteria /PERCIST) in lung cancer, while it is generally acknowledged that combined use of both RESIST and PERSIST criteria might lead to increased accuracy of prediction of treatment response in the earlier treatment stages. Evidently, earlier recognition of tolerance to treatment is vital for reduction of unnecessary toxicity and increase of cost-effectiveness. The barriers of complexity, high cost and limited availability, with regard to the above functional imaging techniques, should nevertheless also be emphasized. Evaluation of response to immune checkpoint inhibitors represents an emerging challenge in the field of immuno-oncology; since the specific patterns of tumor response to these agents cannot be accurately described using conventional imaging criteria, immune-related response criteria (irRC) were first defined in 2009, so as to provide a “common language”, enabling the application of a unified assessment of response to immunotherapy. Controversy with regard to the use of bidimensional measurements (according to the WHO criteria) in the irRC nevertheless ensued; immune-related RECIST 1.1 criteria are now increasingly used in clinical studies. Immune-related response evaluation remains to be implemented in routine practice and seems to represent an emerging endpoint in clinical trials. Monitoring of treatment efficacy using non-imaging modalities Monitoring of response to biomarker-driven therapies targeting specific molecular alterations in the lung cancer genome remains a major challenge in the field of personalized oncology, mainly due to shortage of tissue for the performance of genetic profiling of tumors. Liquid biopsies –detecting circulating tumor cells/CTCs and fragments of cell-free circulating tumor DNA/ctDNA- carry much promise for becoming an excellent and non-invasive alternative to tissue-based testing for the identification of genetic mutations with prognostic or therapeutic relevance. As a blood-based biomarker, ctDNA analysis offers the potential of serial investigations at any time point during the course of treatment, and thus of real-time dynamic monitoring of treatment response and early identification of acquired resistance to treatment or even early detection of recurrence (ideally prior to visible tumor size changes on imaging). The first liquid biopsy test approved by the FDA as a companion diagnostic, cobas[®] EGFR Mutation Test v2, is now increasingly used in routine practice for EGFR mutation testing in patients with advanced non-small cell lung cancer, expanding the access of this population to potential disease-modifying treatments. Comprehensive molecular profiling of tumors using next-generation sequencing (NGS) analysis of ctDNA is another major advancement in personalized lung cancer oncology, with tremendous potential for monitoring of dynamic tumor behavior in response to targeted therapy. Other simple and innovative tools for monitoring of treatment response are also being explored. For example, recent data showed that breath analysis using nanoarray technology may represent a quick and patient-friendly monitoring tool for earlier recognition of treatment failure and thus potentially serve as a surrogate marker for response to lung cancer therapy. Monitoring of treatment-related toxicity Subjective toxicity -which cannot be assessed by current toxicity scales- is frequently under-reported in clinical trials, with important negative implications on drug safety evaluations and patient care in general. Recent data highlight the need to improve the current system of toxicity assessment in the trial setting, mainly via implementation of patient-reported outcomes (PROs). Self-reported (and, ideally, real-time) monitoring of toxicity is increasingly investigated in the setting of routine oncology practice as well. As of yet it remains to be firmly established whether this system may significantly contribute to earlier identification and better management of adverse events, improved patient-physician communication and higher quality of life. Suggested reading 1.Nishino M, Hatabu H, Johnson BE, McLoud TC. State of the art: response assessment in lung cancer in the era of genomic medicine. Radiology 2014; 271: 6-27. 2.Bennett CW, Berchem G, Kim YJ, El-Khoury V. Cell-free DNA and next-generation sequencing in the service of personalized medicine for lung cancer. Oncotarget 2016; doi: 10.18632/oncotarget.11717. 3.Nishino M, Giobbie-Hurder A, Gargano M, Suda M, Ramaiya NH, Hodi FS. Developing a common language for tumor response to immunotherapy: immune-related response criteria using unidimensional measurements. Clin Cancer Res 2013; 19: 3936-43. 4.Di Maio M, Basch E, Bryce J, Perrone F. Patient-reported outcomes in the evaluation of toxicity of anticancer treatments. Nat Rev Clin Oncol 2016; 13: 319-25.
Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.
-
+
OA23 - EGFR Targeted Therapies in Advanced NSCLC (ID 410)
- Event: WCLC 2016
- Type: Oral Session
- Track: Advanced NSCLC
- Presentations: 1
- Moderators:O.T. Brustugun, S. Lu
- Coordinates: 12/07/2016, 14:20 - 15:50, Stolz 2
-
+
OA23.03 - Second-Line Afatinib for Advanced Squamous Cell Carcinoma of the Lung: Analysis of Afatinib Long-Term Responders in the Phase III LUX-Lung 8 Trial (ID 4711)
14:40 - 14:50 | Author(s): K. Syrigos
- Abstract
- Presentation
Background:
Squamous cell carcinoma (SCC) of the lung is a genetically complex and difficult-to-treat cancer. In LUX-Lung 8, afatinib (40mg/day) significantly improved OS (median 7.9 vs 6.8 months, HR=0.81 [95% CI, 0.69‒0.95], p=0.008), PFS (2.6 vs 1.9 months, HR=0.81 [0.69‒0.96], p=0.010) and DCR versus erlotinib (150mg/day) in patients with relapsed/refractory SCC of the lung (n=795). Notably, 12-month (36 vs 28%; p=0.016) and 18-month survival (22 vs 14%; p=0.016) was significantly higher with afatinib than erlotinib, indicating that some patients derive prolonged benefit from afatinib. Here, we present post-hoc analysis of baseline characteristics and efficacy/safety of afatinib in long-term responders (treatment for ≥12 months). Hypothesis-generating analysis of archived tumor samples and blood serum was undertaken to identify possible molecular/clinical biomarkers.
Methods:
Tumor samples were retrospectively analyzed using FoundationOne[TM] next-generation sequencing (NGS); EGFR expression was determined by immunohistochemistry. Pre-treatment serum samples were analyzed with VeriStrat[®], a MALDI-TOF mass spectrometry test, and classified as VeriStrat-Good or VeriStrat-Poor-risk.
Results:
15/398 patients treated with afatinib were long-term responders. Median duration of treatment was 16.6 months (range: 12.3‒25.8). Patient characteristics were similar to the overall dataset (median age: 65 years [range: 54‒81]; male: 80.0%; Asian: 13.3%; ECOG 0/1: 40.0%/60.0%; best response to chemotherapy CR or PR/SD: 53.3%/46.7%; current and ex-smokers: 80.0%). Median PFS was 16.2 months (range: 2.8‒24.0); median OS was 23.1 months (range: 12.9‒31.5). The most common treatment-related AEs (all grade/grade 3) were: diarrhea (73.3%/6.7%); rash/acne (66.7%/6.7%); stomatitis (13%/7%). AEs generally occurred soon after treatment onset (median onset, days [range]: diarrhea 11 [5‒48]; rash/acne 17 [9‒107]; stomatitis 15 [11‒19]). Four patients required a dose reduction to 30mg/day due to treatment-related AEs (diarrhea, rash, stomatitis, diarrhea/rash). NGS was undertaken in 9 patients and details will be presented at the meeting. Genomic aberrations in the ErbB/FGF gene families were identified in 44.4%/55.6% of long-term responders (overall dataset: 29.4%/58.0%). Of 14 patients assessed by VeriStrat, 85.7% were VeriStrat-Good (overall dataset: 61.6%). Immunohistochemistry data was available for two patients; one overexpressed EGFR (≥10% positive cells; H-score ≥200)
Conclusion:
Baseline characteristics of long-term responders to afatinib were similar to the overall dataset. In this sub-group, afatinib conferred a survival benefit of nearly 2 years. Afatinib was well tolerated with predictable and transient AEs that occurred soon after treatment onset. The dataset was too small to identify any clear NGS/VeriStrat predictive signals. Further studies are required to predict long-term response to afatinib.
Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.
-
+
P1.04 - Poster Session with Presenters Present (ID 456)
- Event: WCLC 2016
- Type: Poster Presenters Present
- Track: Pulmonology
- Presentations: 1
- Moderators:
- Coordinates: 12/05/2016, 14:30 - 15:45, Hall B (Poster Area)
-
+
P1.04-021 - Medical Thoracoscopy for the Diagnosis and Management of Pleural Effusions: Results of a Retrospective Analysis (ID 4057)
14:30 - 14:30 | Author(s): K. Syrigos
- Abstract
Background:
Medical thoracoscopy is a minimally invasive procedure utilized mainly by pulmonologists for the diagnosis and management of pleural effusions. The aim of this study was to evaluate the efficacy and safety of medical thoracoscopy when performed by a combined team of pulmonologists and thoracic surgeons in a tertiary university hospital.
Methods:
This is a retrospective cohort analysis of all patients with pleural effusion whο underwent medical thoracoscopy at “LAIKO” Athens General Hospital from June 2013 to December 2014.
Results:
Our study population included 36 patients, 18 males and 18 females, with a mean age of 61 years. All patients were submitted to medical thoracoscopy for the diagnostic evaluation of pleural effusion. Twenty-six patients (26/36, 72.2%) presented with an undiagnosed pleural effusion, six (16.7%) with known malignant, recurrent pleural effusion, three (8.3%) with parapneumonic effusion/empyema and one (2.8%) with idiopathic pleural effusion due to nephritic syndrome. Eighteen patients (18/36, 50%) underwent drainage and pleural biopsy, 9 patients (9/36, 25%) underwent drainage, pleural biopsy and talc pleurodesis, 6 patients (6/36, 16.7%) underwent drainage and talc pleurodesis due to known malignant pleural effusion and 3 patients (3/36, 8.3%) underwent drainage of their parapneumonic effusion/empyema. Among all patients (n=27) who underwent diagnostic pleural biopsy, 2 patients (7.4%) were diagnosed with primary non-small cell lung cancer, 4 (14.8%) with malignant pleural mesothelioma, 3 (11.1%) with metastatic disease of non-thoracic primary origin and 3 (11.1%) with lymphoma, while 1 patient each (3.7%) was diagnosed with tuberculosis, systemic lupus eryhtematosus, chronic inflammation, chronic pleural fibrosis and nephritic syndrome. In 3 patients (3/27, 11.1%) the biopsy was negative. Medical thoracoscopy was non-diagnostic in one patient only (1/27, 3.7%), thus producing a diagnostic yield of 97.3%. With the notable exception of one patient (1/36, 2.8%) who died due to empyema and subsequent sepsis, the remaining post procedural complications were mild, and included subcutaneous emphysema in 6 cases (6/36, 16.7%) and minor bleeding in 3 cases (3/36, 8.3%).
Conclusion:
When performed by a combined team of pulmonologists and thoracic surgeons in a tertiary level hospital, medical thoracoscopy is a relatively safe and efficacious technique for the diagnosis and management of pleural effusions in patients unable to undergo or not requiring surgical intervention.
-
+
P1.05 - Poster Session with Presenters Present (ID 457)
- Event: WCLC 2016
- Type: Poster Presenters Present
- Track: Early Stage NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 12/05/2016, 14:30 - 15:45, Hall B (Poster Area)
-
+
P1.05-074 - Factors Predicting Discordance between Clinical and Surgical-Pathologic Staging in Operable Non-Small Cell Lung Cancer (ID 4083)
14:30 - 14:30 | Author(s): K. Syrigos
- Abstract
Background:
Accurate clinical staging is of the utmost importance for the optimal management of patients with non-small cell lung cancer (NSCLC). The aim of this study was to identify factors associated with discordance between clinical and pathologic staging in patients with operable NSCLC.
Methods:
The medical records of 85 patients with early-stage NSCLC, who had been submitted to thoracotomy followed by surgical resection of the primary tumor and systematic lymph node dissection, were retrospectively reviewed. All patients were staged according to the 7th edition of the TNM staging system. The presence of postoperative upstaging or downstaging was correlated with various demographic and clinicopathological factors, including age, sex, smoking history, tumor histology, tumor size and location.
Results:
Discordance between clinical and surgical-pathologic staging was found in 45/85 cases (52.9%), and the majority of these patients were upstaged (35/85 cases, 41.2%). Patients with IIB and IB clinical stage had the highest (77.8%) and lowest (48.1%) probability of discordance, respectively. With regard to T stage, disagreement between clinical and surgical-pathologic T stage was noted in 22/85 patients (25.9%), including 16 upstaged patients (16/85, 18.8%) and 6 downstaged patients (6/85, 7.1%). Nodal status was altered postoperatively in 39/85 cases (45.9%), including 29 upstaged patients (29/85, 34.1%) and 10 downstaged patients (10/85, 11.8%). The rate of unsuspected mediastinal lymph node involvement (pathologic stage N2) was 14.1% (12/85 patients), despite negative mediastinoscopy findings. Age was the only statistically significant factor independently associated with staging discordance (odds ratio 0.93; 95% confidence interval, 0.87 to 0.99).
Conclusion:
Postoperative upstaging or downstaging was observed in a relatively high percentage of our patient population, and was significantly and independently correlated with patient’s age. These observations warrant confirmation in larger prospective series of patients with early-stage NSCLC.
-
+
P2.01 - Poster Session with Presenters Present (ID 461)
- Event: WCLC 2016
- Type: Poster Presenters Present
- Track: Biology/Pathology
- Presentations: 1
- Moderators:
- Coordinates: 12/06/2016, 14:30 - 15:45, Hall B (Poster Area)
-
+
P2.01-075 - Prognostic Value of Angiogenesis and Cell Adhesion Biomarkers in Non-small Cell Lung Cancer (ID 4890)
14:30 - 14:30 | Author(s): K. Syrigos
- Abstract
Background:
Previous data on the prognostic value of vascular endothelial growth factor (VEGF), E-cadherin and CD44 in non-small cell lung cancer (NSCLC) remain limited and largely controversial. The primary aim of this study was to further investigate these proteins, along with other well-studied biomarkers of prognosis, as predictors of overall survival (OS) in NSCLC.
Methods:
Formalin-fixed and paraffin-embedded tissue specimens from 77 surgical and 41 autopsy cases, were retrieved and evaluated by immunohistochemistry (IHC) for the expression of VEGF, E-cadherin, CD44, p53, Ki-67 and thyroid transcription factor -1 (TTF-1). Immunohistochemical findings were correlated with gender, age, primary tumor location/side, tumor histology and grade and disease stage at diagnosis. The association of clinicopathologic variables and IHC results with overall survival (OS) was assessed –only in the surgical subgroup- by univariate and multivariate Cox regression analysis.
Results:
Mean age of all cases (N=118) was 64.8 years (SD=11.1 years), while the majority were men (104/118, 88.1%). Adenocarcinoma was the predominant histological type (38.1%), while most cases (62.6%) had stage II disease at diagnosis. E-cadherin and CD44 expression were significantly correlated with lower tumor grade and disease stage at diagnosis, both in the total sample and in the surgical and autopsy subgroups. Positive VEGF expression was also correlated with lower grade and stage, in the total sample and the autopsy subgroup, but not in the surgical subset of cases. Positive E-cadherin and CD44 expression were associated with improved OS, both in univariate analysis (p=0.006 and p=0.011, respectively), as well as in the multivariate model, after adjusting for sex, age, tumor location, histology, grade and stage (HR=0.08, 95% CI: 0.09-0.65, p=0.019 and HR=0.07, 95% CI: 0.09-0.63, p=0.017, respectively).
Conclusion:
Our study findings suggest that positive E-cadherin and CD44 immunostaining may represent independent predictors of an improved survival in NSCLC. Larger prospective studies are nevertheless warranted to confirm the independent prognostic value of these candidate biomarkers.
-
+
P2.03b - Poster Session with Presenters Present (ID 465)
- Event: WCLC 2016
- Type: Poster Presenters Present
- Track: Advanced NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 12/06/2016, 14:30 - 15:45, Hall B (Poster Area)
-
+
P2.03b-065 - Serum and Bronchoalveolar Lavage Levels of Adiponectin in Advanced Non-Small Cell Lung Cancer: Results of a Prospective Study (ID 4085)
14:30 - 14:30 | Author(s): K. Syrigos
- Abstract
Background:
Adiponectin (APN) is a major adipokine systhesized by the adipose tissue. A significant body of preclinical evidence has documented the involvement of APN in molecular pathways with a key role in carcinogenesis, while some, but not all, previous clinical studies have suggested the potential value of this molecule as a biomarker of diagnosis and/or prognosis in various malignancies, mainly including obesity-related solid tumors. The main objective of this study was to further explore the prognostic implications of APN levels in the serum and bronchoalveolar lavage of patients with advanced non-small cell lung cancer (NSCLC).
Methods:
Twenty-nine (29) consecutive newly diagnosed NSCLC patients with stage IV disease were prospectively enrolled. Serum and BAL levels of APN were obtained at baseline (before initiation of any therapeutic intervention) and assayed by enzyme-linked immunoassay (ELISA). Serum and BAL levels of APN were correlated with standard clinicopathologic parameters, including gender, age, body mass index (BMI), weight loss, size, histology and grade of the primary tumor, pathologic nodal status and performance status (PS). The association of each study variable with overall survival (OS) was assessed by univariate and multivariate Cox regression analyses.
Results:
Mean age of patients was 65.6 years (SD=10.1 years), while the majority were male (24/29 cases, 82.8%). The predominant histological type was adenocarcinoma (18/29 cases, 62.1% ). PS was 0 and ≥1 in 17/29 (58.6%) and 12/29 (41.4%) patients, respectively. Weight loss more than 10% was noted in 10/29 patients (34.5%). Median serum and BAL APN levels were 911.5 ng/ml and 17710 ng/ml, respectively. No statistically significant correlations were observed between the serum or BAL levels of APN and the clinicopathologic parameters evaluated. Univariate Cox regression analysis showed that APN levels were not significantly associated with survival. The only prognostic factor identified, both by univariate and multivariate survival analysis, was PS.
Conclusion:
The results of our prospective cohort failed to reveal any significant associations between serum or BAL levels of APN and several prognostic parameters (including OS) in stage IV NSCLC, thus confirming most previous observations.
-
+
P2.06 - Poster Session with Presenters Present (ID 467)
- Event: WCLC 2016
- Type: Poster Presenters Present
- Track: Scientific Co-Operation/Research Groups (Clinical Trials in Progress should be submitted in this category)
- Presentations: 2
- Moderators:
- Coordinates: 12/06/2016, 14:30 - 15:45, Hall B (Poster Area)
-
+
P2.06-022 - First-Line Durvalumab plus Tremelimumab vs Platinum-Based Chemotherapy for Advanced/Metastatic NSCLC: Phase 3 NEPTUNE Study (ID 4610)
14:30 - 14:30 | Author(s): K. Syrigos
- Abstract
Background:
Current first-line therapy for advanced EGFR and ALK wild-type NSCLC is associated with poor survival and there remains a significant need for more effective treatments in this population. Blockade of immune checkpoints programmed cell death-1 (PD-1) and cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) represents a promising anticancer therapeutic strategy. In preclinical models, targeting both PD-1 and CTLA-4 provides for non-redundant pathway blockade and potential synergy. Durvalumab (MEDI4736) is a selective, high-affinity, engineered human IgG1 mAb that blocks programmed cell death ligand-1 (PD-L1) binding to PD-1 (IC~50~ 0.1 nM) and CD80 (IC~50~ 0.04 nM). Tremelimumab is a selective human IgG2 mAb inhibitor of CTLA-4. A Phase 1b study of durvalumab + tremelimumab demonstrated encouraging clinical activity and a manageable tolerability profile in advanced NSCLC, with activity observed in patients with high and low/no tumour PD-L1 expression (NCT02000947).
Methods:
NEPTUNE (NCT02542293) is a randomised, open-label, multicentre, global, Phase 3 study. Immunotherapy- and chemotherapy-naïve patients with advanced/metastatic EGFR and ALK wild-type NSCLC (with either PD-L1 high expression [≥25% tumour cells staining for PD-L1 at any intensity] or PD-L1 low/negative expression [<25% tumour cells staining for PD-L1 at any intensity] ) will be randomised (1:1) to durvalumab (20 mg/kg i.v. every 4 weeks [q4w] for up to 12 months) + tremelimumab (1 mg/kg i.v. q4w for up to 4 doses); or standard-of-care platinum-based doublet chemotherapy. The primary endpoint is overall survival (OS). Secondary endpoints are progression-free survival (PFS), objective response rate (ORR), duration of response and proportion of patients alive and progression free at 12 months by investigator assessment (RECIST v1.1); time from randomisation to second progression; OS, PFS and ORR in patients with PD-L1 low/negative NSCLC; safety (CTCAE v4.03) and tolerability; pharmacokinetics; and immunogenicity. Exploratory outcomes include potential biomarkers of response to treatment and impact of subsequent anticancer therapies on OS. Recruitment is ongoing. Figure 1
Results:
Not-applicable
Conclusion:
Not-applicable
-
+
P2.06-033 - Long-Term Safety and Efficacy of Darbepoetin Alfa in Subjects with Advanced Stage NSCLC Receiving Multi-Cycle Chemotherapy (ID 3765)
14:30 - 14:30 | Author(s): K. Syrigos
- Abstract
Background:
Darbepoetin alfa (DA) is an erythropoiesis-stimulating agent (ESA) that has been shown to increase hemoglobin levels and reduce the rate of transfusions in patients with chemotherapy-induced anemia (CIA). Most studies have not shown an association between ESA use and poor outcomes, but some clinical trials have reported increased mortality and/or tumor progression. This trial was therefore designed to address the safety of DA for CIA in patients with non-small cell lung cancer (NSCLC).
Methods:
Study 20070782 is a randomized, double-blind, noninferiority trial to compare DA with placebo, and is enrolling patients with NSCLC with CIA. Eligible patients are ≥ 18 years old with Eastern Cooperative Oncology Group (ECOG) status ≤ 1, stage IV NSCLC, no prior adjuvant/neoadjuvant NSCLC therapy, ≥ 2 cycles first-line chemotherapy planned (≥ 6 weeks total), and screening hemoglobin ≤ 11 g/dL. Approximately 3,000 patients from up to 500 global sites will be randomized 2:1 to DA (500 mcg) or placebo every 3 weeks (Q3W) until disease progression or end of chemotherapy. At hemoglobin > 12 g/dL, study drug is withheld until hemoglobin ≤ 12 g/dL. Transfusions are allowed when necessary. Endpoints include overall survival (OS; primary) and progression-free survival (PFS; secondary), and will be analyzed when ~2,700 deaths have occurred. Additional safety endpoints include tumor response and rate of thromboembolic events. Superiority of DA to placebo in transfusion rates will be tested if noninferiority is achieved for OS and PFS.
Results:
As of April 15, 2016, a total of 2,215 patients have enrolled. The independent data monitoring committee has conducted 9 reviews of unblinded data (which included a planned formal interim analysis at 40% of planned total number of 2,700 deaths to test for harm), and has recommended continuation of the trial without changes.
Conclusion:
Study 20070782 is the largest clinical trial in NSCLC to date, and will provide comprehensive data on the safety and efficacy of DA in patients with CIA.
-
+
P3.02b - Poster Session with Presenters Present (ID 494)
- Event: WCLC 2016
- Type: Poster Presenters Present
- Track: Advanced NSCLC
- Presentations: 2
- Moderators:
- Coordinates: 12/07/2016, 14:30 - 15:45, Hall B (Poster Area)
-
+
P3.02b-003 - Second-Line Afatinib versus Erlotinib for Patients with Squamous Cell Carcinoma of the Lung (LUX-Lung 8): Analysis of Tumour and Serum Biomarkers (ID 5627)
14:30 - 14:30 | Author(s): K. Syrigos
- Abstract
Background:
LUX-Lung 8 compared second-line afatinib (40 mg/day; n=398) and erlotinib (150 mg/day; n=397) in patients with stage IIIB/IV squamous cell carcinoma (SCC) of the lung. PFS (median 2.6 vs 1.9 months, HR=0.81 [95% CI, 0.69–0.96], p=0.010) and OS (median 7.9 vs 6.8 months, HR=0.81 [0.69–0.95], p=0.008) were both significantly improved with afatinib versus erlotinib. Here we report exploratory molecular (n=245) and immunohistochemical (n=288) analyses of tumour samples to assess the frequency of short variants (SVs) and copy number alterations (CNAs) in cancer-related genes and whether these tumour genomic alterations, or EGFR expression levels, have clinical utility as prognostic/predictive biomarkers in patients with SCC of the lung. We also assessed the predictive utility of the prospectively validated VeriStrat®, a serum protein test (n=675).
Methods:
Archived tumour samples were retrospectively analysed using next-generation sequencing (FoundationOne™). Tumour EGFR expression was assessed by immunohistochemistry; EGFR positivity was defined as staining in ≥10% of cells. Pretreatment serum samples were assigned as VeriStrat-Good or VeriStrat-Poor according to a mass spectrometry signature. Cox regression analysis was used to correlate OS/PFS with genomic alterations (individual or grouped into gene families e.g. ErbB family), EGFR expression levels and VeriStrat status.
Results:
The frequency of ErbB family alterations was low (SVs: EGFR 6.5%, HER2 4.9%, HER3 6.1%, HER4 5.7%; CNAs: EGFR 6.9%, HER2 3.7%). No individual genetic alterations, or grouped ErbB family aberrations, were prognostic of OS/PFS. Treatment benefit from afatinib versus erlotinib was consistent in all molecular subgroups. Most tumours were EGFR-positive by immunohistochemistry (afatinib: 82%; erlotinib: 86%). EGFR expression was not predictive of OS or PFS benefit (EGFR-positive PFS: HR=0.76 [0.57‒1.02]; OS: HR=0.84 [0.63‒1.12]; EGFR-negative PFS: HR=0.87 [0.45‒1.68]; OS: HR=0.77 [0.40‒1.51]). In afatinib-treated patients, both PFS (HR=0.56 [0.43‒0.72], p<0.0001) and OS (HR=0.40 [0.31‒0.51], p<0.0001) were improved in the VeriStrat-Good versus the VeriStrat-Poor group. VeriStrat-Good patients had significantly longer OS and PFS when treated with afatinib versus erlotinib (median OS: 11.5 vs 8.9 months, HR=0.79 [0.63‒0.98]; PFS: HR=0.73 [0.59‒0.92]). In VeriStrat-Poor patients there was no significant difference in OS between afatinib and erlotinib (HR=0.90 [0.70‒1.16]). However, there was no significant interaction between treatment arms and VeriStrat classification.
Conclusion:
Despite comprehensive, multifaceted analysis, no biomarkers were identified that predicted the benefit with afatinib over erlotinib in patients with SCC of the lung. Afatinib is a treatment option in this setting irrespective of patients’ tumour genetics or EGFR expression levels. However, patient outcome strongly depends on VeriStrat status.
-
+
P3.02b-019 - TTF-1 Expression as a Predictor of Response to EGFR-TKIs in Patients with Lung Adenocarcinoma (ID 4033)
14:30 - 14:30 | Author(s): K. Syrigos
- Abstract
Background:
Several studies have shown that overexpression of thyroid transcription factor (TTF-1) may be associated with the presence of epidermal growth factor receptor (EGFR) gene mutations and predict survival in patients with non-small cell lung cancer (NSCLC). Nevertheless, the potential significance of TTF-1 immunostaining as a predictor of response to EGFR tyrosine kinase inhibitors (TKIs) has received limited research attention thus far. The aim of this study was to further explore the potential association between TTF-1 immunohistochemical expression and response to EGFR TKIs in patients with lung adenocarcinoma.
Methods:
The medical records of 129 patients with stage IV lung adenocarcinoma, treated at the Oncology Unit of “Sotiria” Athens General Hospital between January 2011 and December 2014, were retrospectively reviewed. All patients had received treatment with EGFR TKIs (erlotinib or gefitinib) and had a known TTF-1 immunohistochemical expression status in formalin-fixed, paraffin-embedded tumour tissue. Demographic and clinicopathological features (age, gender, smoking status and performance status), TTF-1 immunohistochemistry and EGFR mutation status results were correlated to each other as well as with the response rate (RR) to EGFR TKIs, using univariate and multivariate regression analysis.
Results:
Median age of our study population was 68 years (range 26-88 years), while the majority were male (79/129 cases, 61.2%). Patients with EGFR mutant tumors had significantly higher response rates to EGFR TKIs compared to patients with wild-type EGFR tumors (p=0.001). TTF-1 positive staining was weakly associated with the presence of EGFR mutations, without reaching the level of statistical significance (p=0.053). Most importantly, TTF-1 positive staining was not significantly correlated with RR to EGFR TKIs, when gender, age, smoking status, EGFR mutation status and PS were included in the multivariate model.
Conclusion:
The present results failed to demonstrate any independent association between TTF-1 overexpression and the RR to EGFR TKIs in patients with advanced-stage lung adenocarcinoma. Prospective data from larger cohorts of patients are needed to clarify the exact predictive value of TTF-1 immunostaining in this setting.
