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G.V. Scagliotti
Moderator of
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ISS04 - Industry Supported Symposium: Treatment Selection Strategies in Advanced NSCLC - A Symphony of Views - Eli Lilly and Company (ID 438)
- Event: WCLC 2016
- Type: Industry Supported Symposium
- Track:
- Presentations: 6
- Moderators:G.V. Scagliotti, T. Mok
- Coordinates: 12/04/2016, 17:15 - 18:45, Hall C1
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ISS04.01 - Welcome & Introduction (ID 6853)
17:15 - 17:20 | Author(s): G.V. Scagliotti, T. Mok
- Abstract
Abstract not provided
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ISS04.02 - Orchestral Manoeuvres of the Immuno Checkpoints: Targeted or Untargeted Agents? (ID 6854)
17:20 - 17:45 | Author(s): J.G. Aerts
- Abstract
Abstract not provided
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ISS04.03 - Variation on a Theme: Angiogenesis Inhibition Across Treatment Lines (ID 6855)
17:45 - 18:05 | Author(s): M. Pérol
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Abstract not provided
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ISS04.04 - Keys to Biomarker Driven Choices in 2nd Line (ID 6856)
18:05 - 18:25 | Author(s): L. Paz-Arez
- Abstract
Abstract not provided
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ISS04.05 - Is the Score Yet Written? (ID 6857)
18:25 - 18:30 | Author(s): G.V. Scagliotti
- Abstract
Abstract not provided
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ISS04.06 - Discussion: The Unfinished Symphony (ID 6858)
18:30 - 18:45 | Author(s): T. Mok
- Abstract
Abstract not provided
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PR01 - Press Conference (ID 495)
- Event: WCLC 2016
- Type: Press Conference
- Track:
- Presentations: 5
- Moderators:R. Pirker, G.V. Scagliotti
- Coordinates: 12/04/2016, 10:30 - 11:45, Schubert 1
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PR01.01 - Welcome (ID 7198)
10:30 - 10:30 | Author(s): R. Pirker, G.V. Scagliotti
- Abstract
Abstract not provided
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PR01.02 - Shared Decision Making (SDM) and Patient Decision Aids (PDAs) in Lung Cancer: Survey of Patients, Significant Others or Caregivers (ID 7199)
10:30 - 10:30 | Author(s): L. Gaspar
- Abstract
- Presentation
Abstract not provided
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PR01.03 - The ALCF Centers of Excellence Model Delivers a Standard of Care to the Community Similar to Academic and Research Centers (ID 7200)
10:30 - 10:30 | Author(s): R.U. Osarogiagbon
- Abstract
- Presentation
Abstract not provided
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PR01.04 - Mesothelioma Workshop (ID 7201)
10:30 - 10:30 | Author(s): M. Carbone
- Abstract
- Presentation
Abstract not provided
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PR01.05 - E-health and Future Technologies in Evidence Based Nursing Care (ID 7202)
10:30 - 10:30 | Author(s): R. Maguire
- Abstract
Abstract not provided
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SC22 - Selection and Monitoring of Patients for Immune Checkpoint Inhibitors (ID 346)
- Event: WCLC 2016
- Type: Science Session
- Track: Chemotherapy/Targeted Therapy/Immunotherapy
- Presentations: 4
- Moderators:G.V. Scagliotti, J.F. Vansteenkiste
- Coordinates: 12/06/2016, 16:00 - 17:30, Hall C8
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SC22.01 - How Do I Define Optimal Candidates for Immunotherapy in My Practice? (ID 6690)
16:00 - 16:20 | Author(s): J.F. Vansteenkiste, E. Wauters
- Abstract
- Presentation
Abstract:
Over the recent decade, we witnessed important progress in the treatment of patients with advanced NSCLC in three domains. First, cytotoxic chemotherapy, where histology-directed chemotherapy with cisplatin-pemetrexed, followed by pemetrexed maintenance therapy in appropriate candidates, has resulted in a median overall survival (OS) of 16.9 months in adenocarcinoma [1]. Second, the use of tyrosine kinase inhibitors (TKIs) in tumors driven by specific molecular pathways, such as EGFR, ALK and others, has largely improved progression-free survival (PFS) compared to the one with chemotherapy in randomized studies, and had led to OS times of several years in many of these patients [2]. Third, immunotherapy with immune checkpoint inhibitors (ICI) directed against the immunosuppressive molecules programmed cell death 1 (PD-1) and programmed cell death ligand 1 (PD-L1) has been in clinical trials since 2009. At present, the anti-PD-1 antibodies nivolumab (a fully human IgG4 antibody) and pembrolizumab (an engineered humanized IgG4 antibody) have been approved for NSCLC by different regulatory agencies worldwide. EMA approved nivolumab for advanced NSCLC after prior chemotherapy, and pembrolizumab for advanced NSCLC in adults whose tumors express PD-L1 and who have received at least one prior chemotherapy regimen. At the time of writing of this contribution, there were no public randomized study data on the use of these agents in 1[st] line therapy, we will therefore concentrate on the relapse therapy setting. Despite the real progress made by ICI therapy, we must realize that at present only about 20% of the patients respond to single-agent ICI treatment, while 50% have early progression (Checkmate 017 [3]; Checkmate 057 [4]). Moreover, the cost of these drugs is considerable. Hence it is important to define optimal candidates in clinical practice. Elements in this decision are a) clinicopathological factors; b) possible predictive biomarkers; and c) the availability of other treatment choices. As for (a) clinicopathological factors, there is no evidence that age, gender or ethnicity determine activity of ICIs. Smoking history, on the other hand, is strongly associated with better response rate to ICI therapy. Although EGFR oncogene pathway activation has been linked to upregulation of PD-L1 in tumor cells, response rates to ICIs in these patients are generally reported to be lower. In e.g. Checkmate 057, the overall response rate was 19%. It was 22% in smokers vs. 9% in non-smokers, 18% in EGFR-wildtype vs. 11% in EGFR-mutant tumors. Further understanding and refinement of the use of ICIs in tumor with an oncogene driver is needed. (b) A multitude of potential predictive biomarkers of response to PD-1/PD-L1 pathway inhibitors have been reported. In particular, PD-L1 expression in tumor and/or immune cells, the presence of TILs (tumor-infiltrating lymphocytes, CD8+ T-cells in particular), and the overall mutational load in the tumor cells have been linked to activity of ICIs [5]. PD-L1 expression on tumor cells, determined by immunohistochemistry (IHC) staining is by far the one most close to clinical practice for selecting optimal candidates for immunotherapy. This biomarker is quite distinct and less powerful than e.g. EGFR mutation as predictor of efficacy of EGFR TKIs. EGFR mutation is limited to the tumor, it is located in a distinct pathway, and is a yes/no phenomenon. PD-L1 IHC, on the other hand, relates to the tumor and its micro-environment, is only one of the many checkpoints in a complex interaction, and is a gradual phenomenon. Nonetheless, as can be noted from the figure, in most datasets of phase III studies – except Checkmate 017 – PD-L1 IHC predicts efficacy of ICI therapy. We added the large phase I study Keynote 001 to the figure as a very illustrative example: Over the categories of PD-L1 expression, response rate increased from 8% in the lowest to 45% in the highest category [6]. In the Keynote 010 phase III study, the hazard ratio of OS versus chemotherapy was 0.76 in the low-, but 0.54 in the high-expression group [7]. In the Checkmate 057, the OS hazard ratio even was 1.00 in all patients with tumors having PD-L1 <10%. Thus, except for the Checkmate 017 dataset, PD-L1 IHC enriches the response rate and differential OS benefit vs. chemotherapy, and can be used to designate these expensive agents to the optimal candidates. (c) Docetaxel single-agent chemotherapy was the comparator in the phase III studies on relapse therapy. In the meanwhile, progress has been made in conventional relapse therapy as well. In the LUME-Lung 1 trial, the combination of docetaxel and the triple angiogenesis inhibitor nintedanib resulted in a significantly better OS than docetaxel alone – with a difference in median OS of 2.3 months – in patients with adenocarcinoma [8]. In the REVEL study, patients treated with docetaxel plus ramucirumab, a VEGF receptor 2 inhibiting monoclonal antibody, had significantly better OS than those treated with docetaxel alone across all NSCLC histologies [9]. In conclusion, the choice of ICI therapy for relapsing NSCLC needs to be considered in the available treatment options for these patients, and this can be based on clinicopathological factors, predictive biomarkers, and comparison of efficacy of various treatments in specific subgroups. While PD-L1 is not a biomarker with the strength such as e.g. EGFR mutation, it helps to optimize the response rate and differential OS benefit of ICI therapy vs. chemotherapy, and to and can be used to designate these expensive agents to the optimal candidates. Figure Figure 1 References 1. Paz-Ares LG, De Marinis F, Dediu M et al. PARAMOUNT: Final overall survival results of the phase III study of maintenance pemetrexed versus placebo immediately after first-line treatment with pemetrexed plus cisplatin for advanced nonsquamous non-small cell lung cancer. J Clin Oncol 2013; 31: 2895-2902. 2. Mok TS, Wu YL, Thongprasert S et al. Gefitinib or carboplatin-paclitaxel in pulmonary adenocarcinoma. N Engl J Med 2009; 361: 947-957. 3. Brahmer J, Reckamp KL, Baas P et al. Nivolumab versus docetaxel in advanced squamous cell non-small cell lung cancer. N Engl J Med 2015; 373: 123-135. 4. Borghaei H, Paz-Ares L, Horn L et al. Nivolumab versus docetaxel in advanced nonsquamous non-small cell lung cancer. N Engl J Med 2015; 373: 1627-1639. 5. Rizvi NA, Hellmann MD, Snyder A et al. Mutational landscape determines sensitivity to PD-1 blockade in non-small cell lung cancer. Science 2015; 348: 124-128. 6. Garon EB, Rizvi NA, Hui R et al. Pembrolizumab for the treatment of non-small cell lung cancer. N Engl J Med 2015; 372: 2018-2028. 7. Herbst RS, Baas P, Kim DW et al. Pembrolizumab versus docetaxel for previously treated, PD-L1-positive, advanced non-small cell lung cancer (KEYNOTE-010): A randomised controlled trial. Lancet 2016; 387: 1540-1550. 8. Reck M, Kaiser R, Mellemgaard A et al. Docetaxel plus nintedanib versus docetaxel plus placebo in patients with previously treated non-small-cell lung cancer (LUME-Lung 1): A phase 3, double-blind, randomised controlled trial. Lancet Oncol 2014; 15: 143-155. 9. Garon EB, Ciuleanu TE, Arrieta O et al. Ramucirumab plus docetaxel versus placebo plus docetaxel for second-line treatment of stage IV non-small-cell lung cancer after disease progression on platinum-based therapy (REVEL): a multicentre, double-blind, randomised phase 3 trial. Lancet 2014; 384: 665-673.
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SC22.02 - How Do I Monitor for Efficacy? (ID 6691)
16:20 - 16:40 | Author(s): N. Rizvi
- Abstract
- Presentation
Abstract not provided
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SC22.03 - How Do I Monitor for and Treat Immune-Related Events? (ID 6692)
16:40 - 17:00 | Author(s): A. Spira
- Abstract
- Presentation
Abstract:
Immunotherapy (IT) has become one of the most potent new treatments for all cancers, particularly non small lung cancer. However, it has a unique toxicity profile different than most therapies (chemotherapy; biologic; targeted therapy) than most oncologists are familiar with, specifically immune related adverse events; irAE. These toxicities may be acute but also can occur weeks and months after starting or even stopping therapy. Given the prolonged duration that patients may be exposed to these drugs, they become important to manage over a short and long period. Further, given the responses and the relative milder toxicity compared with traditional chemotherapy agents, the older patient population may be exposed to these agents at a somewhat higher frequency. The use of immunomodulatory drugs to counter irAE toxicity will be discussed as to how it affects efficacy of immunotherapy. This lecture will focus on: Timeframe and monitoring for immune related toxicity (with special attention paid towards pulmonary, gastrointestinal and endocrinopathies) using the appropriate immunosuppressive drugs Management of toxicities related to IT Decision making on re-exposure to drug after iRAE Patient education Toxicities associated with combination IT drugs that may be used in the future or on clinical trials
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SC22.04 - How Can Immunotherapy Be Implemented in a Cost-Effective Strategy? (ID 6693)
17:00 - 17:20 | Author(s): C. Zielinski
- Abstract
- Presentation
Abstract:
“How Can Immunotherapy be Implemented In a Cost-Effective Strategy?” Christoph Zielinski, Director, Clinical Division of Oncology and Chairman, Department of Medicine I, and Comprehensive Cancer Center, Medical University Vienna – General Hospital, Vienna, Austria, Central European Cooperative Oncology Group (CECOG) When talking about immunotherapy and its cost-effectiveness, the story of disharmony between the magnitude of clinical benefit and the cost-effectiveness of certain drugs clearly emerges. I will try to illustrate this by the following arguments and data: The total health care costs of cancer per person varies widely within EU countries not only concerning outpatient and primary care, but also inpatient care and particularly drug expenditures. Cancer drug-related health care costs, thus differ between less than € 10.- per person up to over € 50.- per person. This divergence has been described previously and put into context with cancer outcomes (1) as well as cancer-associated mortality (2). Therefore, the European Society for Medical Oncology decided to create a magnitude of clinical benefit scale (ESMO-MCBS) “in order to promote high quality, rational, responsible and affordable cancer care wanting to highlight treatments which bring substantial improvements to the duration of survival and/or the quality of life of cancer patients” (3). It was intended that the scale was used for accelerated reimbursement evaluation. Factors taken into account for the ESMO-MCBS were particularly overall survival and/or progression-free survival as assessed by hazard ratios, quality of life, toxicity of the compound in question and the prognosis of the individual condition. Costs were not analysed in view of their significant heterogeneity across Europe. While generating two different scales for the curative versus the non-curative setting, a couple of rules were followed regarding the performed analyses: the priority was a strong level of evidence from large phase III studies with a careful analysis of each control arm and the identification of endpoints. For the required HR, the lower limit of the 95% CI was used to take into account the variability of the estimate. Before being published, the scale and its outcomes were broadly tested and evaluated in and by various institutions. The first full-length field testing (FT-MCBS) of the ESMO-MCBS was published recently (4) in which the results of non-small cell lung cancer (NSCLC) corresponded well with the original ESMO-MCBS. Regarding the use of the immune checkpoint inhibitor Nivolumab, the FT-MCBS generated the highest grade (i.e. “5”) for squamous NSCLC according to data generated within the Checkmate 017-Trial whereas a grade “4” was given for non-squamous NSCLC, as assessed in the Checkmate 057-Trial. Thus, the immune checkpoint inhibitor Nivolumab has acquired the highest or almost highest degree in the magnitude of clinical benefit, as assessed by the FT-MCBS scale. Soon after market introduction, concerns about the financial toxic dose of immune checkpoint inhibitors emerged leading to the rejection of NICE of Nivolumab in the second-line-treatment of NSCLC, whereas – in contrast - the Scottish authorities decided to include Nivolumab into their reimbursement strategies. Very recent analyses on this very topic showed that Nivolumab was not cost effective versus Docetaxel in the second-line-treatment of NSCLC based upon data generated in Checkmate 057-Trial. However, cost effectiveness could be very well reached by including and stratifying patients according to PD-L1 testing and the use of Nivolumab in PD-L1 overexpressing tumors on one side or – in statistical models - by the reduction of drug costs on the other. Either of these strategies would improve the cost effectiveness of Nivolumab (5, 6) Scientifically, however, the doubt remains to linger whether PD-L1 would be an optimal biomarker resulting in appropriate decision making for the choice of compound optimally suitable for the treatment of NSCLC without unjustly excluding patients who might have benefitted due to other factors from treatment: Thus, it is well known that certain somatic mutations occur more frequently in very special tumors than in others (7). Along this line, the efficacy of Nivolumab correlated with higher non-synonymous mutation burden in the Checkmate 063-Trial population (8). Therefore, it seems correct to conclude that we still have a long way to go to fully understand biomarkers predictive for the outcome of an optimal treatment of NSCLC with immune checkpoint inhibitors. Accordingly, appropriate analyses necessary for biomarker identification might translate into cost effectiveness. Such analyses might result in a primarily increased diagnostic cost, but lead to an ameliorated patient selection and, thus, ameliorated cost effectiveness in the appropriate use of immune checkpoint inhibitor treatment in NSCLC. In the meantime, the scientific community remains fascinated by the insights and results which are generated by the use of these compounds in a variety of diseases including NSCLC. References 1. Jedrzejewski M. et al., The Oncologist 20: 28, 2015; 2. .Ades F. et al., Ann. Oncol. 24: 2897, 2013; 3. N.I. Cherny et al., Ann. Oncol. 26: 1547, 2015; 4. B. Kiesewetter et al., ESMO Open 1: e000066, 2016; 5. K. Matter-Walstra et al., J. Thoracic Oncol., 2016, ePub.: http://dx.doi.org/10.1016/j.jtho.2016.05.032; 6. P.N. Aguiar et al., J. Clin. Oncol. 34, abstr. 9033, 2016; 7. L.B. Alexandrov et al., Nature. 22: 415, 2013; 8. N.A. Rizvi et al., Science 2015, ePub.: pii:aaa1348
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Author of
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ED11 - Advanced NSCLC: State-of-the-Art Treatment (ID 280)
- Event: WCLC 2016
- Type: Education Session
- Track: Advanced NSCLC
- Presentations: 1
- Moderators:C. Manegold, C. Zhou
- Coordinates: 12/07/2016, 11:00 - 12:30, Hall C8
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ED11.02 - Systemic Therapy for Advanced Non-Oncogene-Driven NSCLC (ID 6486)
11:25 - 11:50 | Author(s): G.V. Scagliotti
- Abstract
- Presentation
Abstract not provided
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ISS04 - Industry Supported Symposium: Treatment Selection Strategies in Advanced NSCLC - A Symphony of Views - Eli Lilly and Company (ID 438)
- Event: WCLC 2016
- Type: Industry Supported Symposium
- Track:
- Presentations: 2
- Moderators:G.V. Scagliotti, T. Mok
- Coordinates: 12/04/2016, 17:15 - 18:45, Hall C1
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ISS04.01 - Welcome & Introduction (ID 6853)
17:15 - 17:20 | Author(s): G.V. Scagliotti
- Abstract
Abstract not provided
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ISS04.05 - Is the Score Yet Written? (ID 6857)
18:25 - 18:30 | Author(s): G.V. Scagliotti
- Abstract
Abstract not provided
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MTE10 - Unique Biologic Aspects of Tobacco-Induced Lung Cancer (Ticketed Session) (ID 304)
- Event: WCLC 2016
- Type: Meet the Expert Session (Ticketed Session)
- Track: Biology/Pathology
- Presentations: 1
- Moderators:
- Coordinates: 12/06/2016, 07:30 - 08:30, Schubert 1
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MTE10.01 - Unique Biologic Aspects of Tobacco-Induced Lung Cancer (ID 6557)
07:30 - 08:30 | Author(s): G.V. Scagliotti
- Abstract
- Presentation
Abstract:
Lung cancer is the leading cause of cancer death worldwide and cigarette smoking is a major causative environmental factor. Some unique biologic profiles are associated to tobacco-induced lung cancer, including clinical, pathological and genetic features. Lung cancer in never smokers (up to 20% of cases worldwide) has been suggested to represent a distinct disease, compared to tobacco-induced lung cancer. Cigarette smoke is a mixture of more than 5000 chemical compounds, among which more than 60 are recognized to have a specific carcinogenic potential. Carcinogens and their metabolites (i.e., N-nitrosamines and polycyclic aromatic hydrocarbons, among others) can activate multiple pathways, contributing to pulmonary cell transformation in different ways. Nicotine, originally thought to be responsible for tobacco addiction, only, is also involved in tumor promotion and progression with anti-apoptotic and indirect mitogenic properties (Tonini et al. Future Oncol 2013;9:649-55). Preclinical models were employed to define epigenomic alterations and gene expression profiles in respiratory epithelia exposed to cigarette smoke condensate. In a study, smoke condensate significantly repressed miR-487b, that directly targets several genes, including SUZ12, BMI1, WNT5A, MYC, and KRAS. Such repression correlated with overexpression of the above targets in lung cancer and coincided with DNA methylation within the miR-487b genomic locus, indicating this molecule as a tumor suppressor microRNA silenced by epigenetic mechanisms during tobacco-induced pulmonary carcinogenesis. These findings may potentially pave the way for DNA demethylating agent treatment, in order to re-activate miR-487b in lung cancer therapy (Xi et al. JCI 2013; 123:1241-61). Among other effects of cigarette smoking, a synergy was described with the aryl hydrocarbon receptor (AHR), which is partially responsible for tobacco-induced carcinogenesis through incompletely understood mechanisms. It was reported that smoking induces AHR activating ligands, which in turn induced adrenomedullin both in vitro and in vivo, thus significantly contributing to the carcinogenicity of tobacco-activated AHR. These effects were not reproduced in fibroblasts and mice lacking the aryl hydrocarbon receptor (Portal-Nuñez et al. Cancer Res 2012; 72:5790-800). Genetic factors involved in tobacco-induced lung cancers have been widely investigated to determine the genetic susceptibility to lung cancer, including epigenomic alterations (Fujimoto et al. PlosOne 2010;5:e11847. Liu et al. Oncogene 2010;29:3650-64). In addition, tobacco-induced lung cancer is characterized by a deregulated inflammatory microenvironment (Spitz et al. Cancer Epidemiol Biomark Prev 2012; 21:1213-21). Therefore variants in inflammation pathway associated genes, as well as a number of genetic polymorphisms have been identified as putative candidates predisposing to lung cancer development. The effects of single polymorphisms on lung cancer development risk have been investigated, with inconsistent results. Most currently identified polymorphisms involve genes encoding proteins associated with the metabolic processing of tobacco smoke carcinogens and the repair of mutations induced by those carcinogens. Polymorphisms on chromosomes 5p15.33, 6p21, and 15q24-25.1 were identified, being the former specifically associated to a higher risk for adenocarcinoma (Yokota et al. Adv Cancer Res 2010;109:51-72). Regarding inflammation genes, analyzing a comprehensive panel of over 11,000 inflammation pathway single-nucleotide polymorphisms (SNP), six SNPs were significantly (p < 0.05) associated to a higher risk of lung cancer development, including two SNP variants in former smokers (BCL2L14) and in current smokers (IL2RB) (Spitz et al. Cancer Epidemiol Biomark Prev 2012; 21:1213-21). The above genetic alterations are observed in all histological subtypes of lung cancer with several differences, especially between small cell lung carcinoma (and the other neuroendocrine tumors) and non-small cell lung cancers. Though all lung cancers are generally tobacco related, changes of incidence of different histological types (with an increase of adenocarcinoma in both sexes) are well known, reflecting modifications of smoking habits, cigarette types, filter types and content of tar, among others. Wide sequencing of single cancer histotypes has provided a relatively complete map of most common alterations in each tumor. In adenocarcinoma, a mean exonic somatic mutation rate of 12.0 events/megabase was identified, which included most previously reported genes in adenocarcinoma as significantly mutated, as well as recurrent mutations in U2AF1, RBM10 and ARID1A genes, and structural rearrangements within EGFR and SIK2 kinases (Imielinski et al. Cell 2012; 150, 1107–1120). Regarding squamous cell carcinoma, the Cancer Genome Atlas Network profiled 178 tumors and found complex genomic alterations, with a mean of 360 exonic mutations, 165 genomic rearrangements, and 323 segments of copy number alteration per tumor. Recurrent mutations were found in 11 genes, with TP53 mutations occurring in nearly all specimens and novel alterations affecting a proportion of cases, including HLA-A class I major histocompatibility gene, NFE2L2, KEAP1, phosphatidylinositol-3-OH-kinase pathway genes, CDKN2A, RB1 and specific squamous differentiation genes (Cancer Genome Atlas Res Network. Nature 2012;489:519-525). As far as small cell lung cancer is concerned, high mutation rates (up to 8.6 non-synonymous mutations per million base pairs) were identified. Of these, up to 28% were found to be C:G>A:T transversions, a type of alteration associated to heavy smoking, although the smoking history was not correlated with the type and number of mutations. Other genes exhibiting mutations and inactivating translocations included the histone acetyltransferase genes CREBBP and EP300, genes with functional roles in the centrosome (ASPM, ALMS1 and PDE4DIP), in the RNA-regulating gene XRN1 and the tetraspanin gene PTGFRN. Damaged genes were commonly found, including the known TP53, RB1, but also TP73, CREBBP and COL22A1, as well as FMN2 and NOTCH family genes (mostly inactivation in the latter) (George et al. Nature 2015; 524: 47–53). Whether the identified genetic signatures and peculiar biological features will produce a corresponding reproducible therapeutic “signature” is still not the case, but the way is paved for stratifying patient groups based on their unique pathological and genetic tumor characteristics, among different histotypes and also within individual neoplastic variants. The future challenge will be to define the biological profile of immunocheckpoint molecule expression in tobacco related lung cancers, in order to identify a reliable predictive marker of response to treatments targeting PD1 or PDL1, in relationship with the different mutational burden and immunological status of individual cases.
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OA22 - Novel Trials and Biomarkers in Malignant Pleural Mesothelioma (ID 403)
- Event: WCLC 2016
- Type: Oral Session
- Track: Mesothelioma/Thymic Malignancies/Esophageal Cancer/Other Thoracic Malignancies
- Presentations: 1
- Moderators:H. Pass, N. Van Zandwijk
- Coordinates: 12/07/2016, 14:20 - 15:50, Strauss 3
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OA22.02 - Nintedanib plus Pemetrexed/Cisplatin in Patients with MPM: Phase II Findings from the Placebo-Controlled LUME-Meso Trial (ID 4191)
14:30 - 14:40 | Author(s): G.V. Scagliotti
- Abstract
- Presentation
Background:
Standard first-line treatment for patients with unresectable malignant pleural mesothelioma (MPM) is pemetrexed/cisplatin, yielding a median overall survival (OS) of only ~1 year, thus new approaches are required. As demonstrated by the bevacizumab MAPS study, inhibition of the VEGF pathway is of interest as a treatment approach for MPM. Nintedanib is an oral, triple angiokinase inhibitor of VEGFR, PDGFR and FGFR. This study will evaluate the efficacy and safety of nintedanib plus pemetrexed/cisplatin in patients with advanced MPM.
Methods:
Patients with unresectable MPM (chemo-naïve, ECOG PS 0–1) were stratified by histology (epithelioid/biphasic) and randomised (1:1) to receive up to 6 cycles of pemetrexed (500 mg/m[2])/cisplatin (75 mg/m[2]) on Day 1 plus nintedanib (200 mg bid)/placebo on Days 2–21. Patients without disease progression received maintenance treatment with nintedanib/placebo. The primary endpoint was progression-free survival (PFS).
Results:
87 patients were randomised to receive pemetrexed/cisplatin, plus nintedanib/placebo. Patient characteristics were comparable between the groups. PFS was longer in the nintedanib vs the placebo arm, in both the overall study population and in epithelioid patients (Table 1). Preliminary OS data also favour nintedanib. All patients experienced at least one adverse event (AE, any grade), with 7% of patients in the nintedanib arm discontinuing due to AEs, vs 15% with placebo. Serious AEs occurred in 36% vs 42% of patients in the nintedanib and placebo arms, respectively. The most common ≥grade 3 AEs occurring in nintedanib vs placebo patients were neutropenia (34% vs 10%), ALT increase (14% vs 2%) and gamma glutamyltransferase increase (14% vs 0%).
Conclusion:
Nintedanib plus pemetrexed/cisplatin demonstrated clinical efficacy with improved PFS and a tolerable safety profile in patients with unresectable MPM. Based on these promising findings, this Phase II study was extended to a confirmatory Phase III trial, which is currently enrolling patients. Clinical trial identifier: NCT01907100.
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PR01 - Press Conference (ID 495)
- Event: WCLC 2016
- Type: Press Conference
- Track:
- Presentations: 1
- Moderators:R. Pirker, G.V. Scagliotti
- Coordinates: 12/04/2016, 10:30 - 11:45, Schubert 1
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PR01.01 - Welcome (ID 7198)
10:30 - 10:30 | Author(s): G.V. Scagliotti
- Abstract
Abstract not provided
