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Manuel Dómine

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    GR02 - Improving Patients Quality of Life During Treatment of Metastatic Disease (ID 30)

    • Event: WCLC 2019
    • Type: Grand Rounds Session
    • Track: Advanced NSCLC
    • Presentations: 4
    • Now Available
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      GR02.01 - How Can We Incorporate Exercise Practices into Patient's Lives? (Now Available) (ID 3304)

      15:15 - 16:45  |  Presenting Author(s): Clarissa Mathias

      • Abstract
      • Presentation
      • Slides

      Abstract

      Physical activity is any movement using skeletal muscles. There have been over 16 studies examining physical activity and lung cancer risk, 12 cohorts and four case-control studies have examined the association between physical activity and lung cancer. When stratifying by study design, the pooled risk reduction amongst the 12 cohort studies is 23%, and amongst 4 case-control studies, a pooled risk reduction of 38%1. Among In a meta-analysis of 11 studies comparing highest versus and lowest levels of leisure-time physical activity, including odds ratios from studies in which the association between physical activity and cancer prevention was adjusted for smoking intensity: moderate-intensity physical activity was associated with a statistically significant risk reduction in lung cancer incidence, OR=0.87 (95% CI: 0.79–0.95), and vigorous-intensity physical activity was associated with a statistically significant risk reduction in lung cancer incidence, OR=0.70 (95% CI: 0.62–0.79).

      During exercise, particularly moderate-intensity aerobic exercise, T-cell populations transiently, NK cell populations and activity, and neutrophil quantity and activity transiently rise2. Exercise or physical activity haves a profound effect on macrophage physiology, including phagocytosis, chemotaxis, metabolism and anti-tumor activity. In murine models of acute exercise, peritoneal macrophage phagocytosis was increased in vitro, relative as opposed to sedentary conditions3. Although these effects are transient during an acute bout of exercise, the repetitive effects may produce a cumulative (training) effect. Chronic bouts of physical activity have been associated with an inverted ‘J-curve’ such that optimal immune function is achieved with moderate-intensity physical activity and sedentary and vigorous-intensity below optimal immune-system function.

      Physical activity is also a useful adjunct to improve the deleterious sequelae experienced during cancer treatment including fatigue, muscular weakness, deteriorated functional capacity, and many others. There is a growing base of evidence that suggests engaging in exercise, such as brisk walking, yields fewer symptoms and side effects during treatment and retards delays the rate at which physiologic systems are affected4. The mechanistic models hypothesized that includes pathways relating to sex hormones, metabolic hormones, inflammation and adiposity, immune function, oxidative stress, DNA repair, and xenobiotic enzyme systems. During cancer treatment, deconditioning of the cardiovascular and pulmonary system is common and is associated with diminished levels tolerance to of physical activity. However, it appears that the adaptive capacity of the cardiorespiratory system to exercise training remains intact during treatment. Among In a meta-analysis of 17 high-quality studies, aerobic fitness—a marker of cardiorespiratory function—improved significantly in cancer survivors during treatment over the exercise intervention period. Muscle Ffatigue and muscle weakness are also common sequelae of cancer treatment, but may be amenable to exercise training. A meta-analysis of randomized controlled trials concluded that both upper body and lower body strength improve as a result of exercise training during cancer treatment, with d=0.39 (95% CI: 0.12–0.65), and d=0.24 (95% CI: 0.07–0.41), respectively5. Strength improvements in the absence of muscle hypertrophy suggest that the adaptations resulting from strength training may be largely attributable to neural adaptations from better motor unit activation (recruitment, discharge rate), synchronization, and cross education. Neural adaptations occur early on in aduring a strength training program and may explain strength improvements in most short-term training studies. Mmoderate intensity activity may optimize immune activity and promote an anti-inflammatory state. Several biomarkers of immunologic function and inflammation exist including neutrophil and lymphocyte counts, natural killer cell activity, C-reactive protein, IL-6, IL-10, and TNF- alpha. It remains unclear what benefits exercise may have on immune system function after cancer treatment6.

      Despite the large volume of studies examining muscular strength among cancer survivors during treatment, few studies have examined the role of strength training among those with cancer cachexia7. It is interesting, Interestingly, given the success of resistance training among cancer survivors, to increaseincreasing upper and lower body strength that use of this modality among cancer survivors with cachexia is not more commonly studied.

      Despite the favorable profile of physical activity along the cancer continuum, many research gaps still exist. Elucidating the optimal dose of physical activity necessary to maximize the reduction in cancer risk of cancer and the optimal dose of physical activity necessary to improve specific physiologic systems, or treatment-specific side effects is warranted. In July 2010, an expert panel from the American College of Sports Medicine reviewed current studies of exercise training and cancer survivorship and released a roundtable consensus statement, concluding that exercise training is “safe during and after cancer treatments and results in improvements in physical functioning, quality of life, and cancer-related fatigue”8.

      Incorporation of exercise practices should, therefore, be advised and stimulated to prevent lung cancer, decrease treatment related side effects, rehabilitate survivors and possibly help during the cachexia period. Interaction between medical oncologists, thoracic surgeons, pulmonologists, physical therapist and sports medicine experts is mandatory for an optimal design of needed trials that will answer several opened questions related to this topic.

      References

      1. Emaus A et al. Physical activity and lung cancer prevention. Recent Results Cancer Res. 2011; 186:101–133

      2. Shephard RJ et al. Effects of exercise and training on natural killer cell counts and cytolytic activity: a meta-analysis. Sports Med. 1999; 28(3):177–195

      3.Woods JA, et al. Exercise-induced modulation of macrophage function. Immunol Cell Biol 78: 543-553, 2000

      4. Schmitz KH, et al. American college of sports medicine roundtable on exercise guidelines for cancer survivors. Med Sci Sports Exerc. 2010; 42(7):1409–1426

      5. Speck RM, et al. An update of controlled physical activity trials in cancer survivors: a systematic review and meta-analysis. J Cancer Surviv. 2010; 4(2):87–100

      6. McTiernan A. Mechanisms linking physical activity with cancer. Nat Rev Cancer. 2008; 8(3): 205–211

      7. Bossola M, et al. Cancer cachexia: it’s time for more clinical trials. Ann Surg Oncol. 2007

      8. Schmidt KH, et al. American College of Sports Medicine roundtable on exercise guidelines for cancer survivors. Med Sci Sports Exerc 42: 1409-1426, 2010

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      GR02.02 - What is the Best Management of Targeted Therapy Toxicity? (Now Available) (ID 3305)

      15:15 - 16:45  |  Presenting Author(s): Glenwood D. Goss

      • Abstract
      • Presentation
      • Slides

      Abstract

      GR02.02 - What Is the Best Management of Targeted Therapy Toxicity?

      15:35 - 15:55 | Presenting Author(s): Glenwood D. Goss

      Over the past decade, the discovery of oncogenic driver mutations in NSCLC and the subsequent advent of targeted therapies against these genomic alterations have significantly altered the management of adenocarcinoma of the lung for a significant proportion of patients. While most oncogenic driver mutations are rare, some exist in up to 50% of specific demographic groups, and together, oncogene-driven disease represents the majority of adenocarcinoma cases (1). Targeted therapies permit directed anti-neoplastic efficacy, with less systemic adverse events than chemotherapy. However, these agents are not without their own unique toxicities that must be managed for optimal drug compliance and therapeutic benefit. This talk will focus on the management of toxicities resulting from the targeting of aberrant pathways and common driver mutations in adenocarcinoma of the lung.

      We define targeted agents as pharmaceutical interventions directed specifically at one or more of the actionable genomic alterations that result in oncogenic phenotypes (proteins, signalling, etc.). Given the breadth of agents to be tested in this indication, the primary focus of the talk will be on approved (versus experimental) and commonly used agents, including small molecules and antibodies, but not antibody-drug conjugates. Genomic alterations to be addressed include at minimum the ERBB family of genes, KRAS, ALK, ROS-1, PI3K, VEGF and BRAF.

      For each agent directed against one of these aforementioned alterations, we will approach management of toxicity by contrasting the normal function of the pathway with adverse events associated with inhibition of this pathway. The management of the most frequent and serious adverse events of the pathway blockade will be the focus of the presentation.

      In conclusion, targeted therapies have had a profound impact on progression-free survival in a significant proportion of patients with metastatic adenocarcinoma of the lung, however they can be associated with a unique set of significant toxicities. The appropriate management of these toxicities may often determine whether a patient derives benefit or not from a targeted therapy, as toxicities can impact dose, frequency of delivery and compliance. Moving forward, increasing the specificity of targeted genomic alteration blockade is required to limit unwanted effects on wild-type proteins. The future of targeted therapy mandates that we devise newer agents with minimal toxicity.

      1. Cancer Genome Atlas Research Network. Comprehensive molecular profiling of lung adenocarcinoma. Nature. 2014 Jul 31;511(7511):543–50.

      2. Kowanetz M. Vascular Endothelial Growth Factor Signaling Pathways: Therapeutic Perspective. Clin Cancer Res. 2006 Sep 1;12(17):5018–22.

      f1_sml.pngf2_sml.jpg

      Image 1: known (red) and putative (blue) driver mutations in adenocarcinoma of the lung, TGCA sample (1)

      Image 2: VEGF signaling in cancer and targets of inhibition.(2)

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      GR02.03 - What Is the Best Management of Immunotherapy Toxicity? (Now Available) (ID 3306)

      15:15 - 16:45  |  Presenting Author(s): Jean-Marie Michot

      • Abstract
      • Presentation
      • Slides

      Abstract

      Introduction.

      The consultations and advices of the organ specialists for immune-related adverse events (irAEs) management can be of great help. The oncologist who uses the immune-checkpoint inhibitors (ICIs) should in his clinical practice be surrounded by different organ specialists that will support him in the management of irAEs1–3.

      Although guidelines provide detailed algorithms for the management of irAEs4–6, few studies have assessed the real-life medical need of the oncology community. We propose here to report the activity of the immunoTOX assessment board to point the medical needs of oncologists in real life.

      Patients and methods.

      Organization of the immunoTOX assessment board.

      The ImmunoTOX assessment board is an academic group of physicians based at Gustave Roussy, Villejuif and at Paris-Sud University AP-HP Hospital, bringing together physicians specialized in the management of immunological toxicities1. Are present oncologists, pharmacovigilance pharmacists, internists and various specialists from expert bodies in the management of immunological toxicities (dermatologist, nephrologist, gastroenterologist, cardiologist, rheumatologist, hepatologist, neurologist, ear nose and throat specialist, ophthalmologist, hematologist, lung specialist and endocrinologist)

      Results.

      Over the period studied, 398 requests were sent to the immunoTOX board, for 356 patients. The median time between the occurrence of irAE and the immunoTOX board discussion was 35 days (IQ 13-72). The main requests to the immunoTOX board were about a diagnostic opinion on the relationship between immunotherapy and the side effect (n = 148, 37% of cases), followed by an opinion on the possibility of reintroduction the ICI in a patient after previous irAE (n = 109, 27% of cases), followed by an opinion about the management of a complex immunological toxicity (n = 100, 25% of cases), and by the possibility of starting an ICI in a patient with comorbidities (n = 41, 10% of cases).

      A certain or probable or possible causal relationship between immunotherapy and side-effect was found in 273/356 (77%) of patients. Among the 273 irAEs investigated, the main organ categories were distributed in the lung (n = 58, 21.2%), the gastrointestinal tract (n = 36, 13.2%), the liver (n = 33, 12.1%). %), musculoskeletal (n = 27, 9.9%) and nervous system (n = 23, 8.4%) (figure 1A).

      diapositive1.jpg

      The question of retreatment was 27% of the requests addressed to the immunoTOX board. The question of retreatment involved the possibility of resuming immunotherapy after prior irAE, which was grade 1-2 in 49% of cases and grade 3-4 in 51% of cases. The immunoTOX board gave a favorable recommendation for retreatment with caution for use in 65% of cases, a notice for maintaining temporary hold in 15% of patients, and a notice in favor of permanent discontinuation in 20% of cases.

      The requests question of the possibility of initiation of immunotherapy in a patient with comorbidities was one in ten. In patients with comorbidities, the immunoTOX board was in favor of initiating immunotherapy and recommended a precaution for use without formal contraindication in 93% of cases.

      Conclusion.

      The Immunotox board highlights the prominent real-life medical needs in the field of management of immunological toxicities. Questions rely mainly on toxicities affecting lung, digestive tract, hepatic and neuro-muscular system. When discussing a readministration or initiation of ICI in patients with autoimmune comorbidities, the Immunotox board was generally not opposed to give immunotherapy. A model of multidisciplinary management with oncologists working in close collaboration with organ specialists may guarantee to the patient the access to the ICI. This report will provide a basis of medical needs to define future strategies in prospective clinical trials of immunological toxicities management.

      Acknowledgement: The author thank the patients and their families and all investigators and site personnel. The authors thank Janine Nda, Cécile Geniez and Stéphanie Demirdjian and Sandrine Thorel for their assistance in management of patients.

      Figures legends.

      Figure 1. Distribution of irAEs organ categories (figure 1A) and irAEs types (figure 1B) registered by the immunoTOX board assessment. In the figure 2A are showed irAEs with occurrence ≥ 3.

      Figure 2. Characteristics of immune-related adverse events registered by the immunoTOX board assessment (among the 273 irAEs registered by the immunoTOX assessment board).

      CLS: Capillary leak syndrome

      CRS: Cytokine Release syndrome

      HPD: Hyperprogressive disease

      Hem-irAEs: Haematological immune-related adverse events

      irAEs: Immune-related adverse events

      References.

      1 Champiat S, Lambotte O, Barreau E, et al. Management of immune checkpoint blockade dysimmune toxicities: a collaborative position paper. Ann Oncol Off J Eur Soc Med Oncol ESMO 2016; 27: 559–74.

      2 Naidoo J, Zhang J, Lipson EJ, et al. A Multidisciplinary Toxicity Team for Cancer Immunotherapy–Related Adverse Events. J Natl Compr Canc Netw 2019; 17: 712–20.

      3 Cappelli LC, Shah AA, Bingham CO. Immune-Related Adverse Effects of Cancer Immunotherapy— Implications for Rheumatology. Rheum Dis Clin N Am 2017; 43: 65–78.

      4 Brahmer JR, Lacchetti C, Schneider BJ, et al. Management of Immune-Related Adverse Events in Patients Treated With Immune Checkpoint Inhibitor Therapy: American Society of Clinical Oncology Clinical Practice Guideline. J Clin Oncol Off J Am Soc Clin Oncol 2018; : JCO2017776385.

      5 Haanen JB a. G, Carbonnel F, Robert C, et al. Management of toxicities from immunotherapy: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol Off J Eur Soc Med Oncol 2017; 28: iv119–42.

      6 Puzanov I, Diab A, Abdallah K, et al. Managing toxicities associated with immune checkpoint inhibitors: consensus recommendations from the Society for Immunotherapy of Cancer (SITC) Toxicity Management Working Group. J Immunother Cancer 2017; 5: 95.

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      GR02.04 - Immunotherapy: Hyperprogression and Treatment Beyond Progression (Now Available) (ID 3307)

      15:15 - 16:45  |  Presenting Author(s): David R Gandara

      • Abstract
      • Presentation
      • Slides

      Abstract

      Hyperprogression/Fast Progression and Treatment Beyond Progression: Unresolved Issues with Checkpoint Immunotherapy

      David R Gandara, MD

      University of California, Davis Comprehensive Cancer Center

      Sacramento, CA

      The tidal wave of checkpoint immunotherapy (CPI) over the last few years has both opened up a myriad of new treatment options for patients with lung cancer. There are many unique aspects of these PD-1- and PD-L1-directed therapies, turning oncologists into both immunologists and endocrinologists, to better manage a large variety of immune related adverse events. This presentation with address two other aspects of CPI which currently remain both poorly understood and controversial: Hyperprogression/Fast Progression and Treatment Beyond Progression.

      Hyperprogression/Fast Progression (HPD/FP): A phenomenon of accelerated tumor growth, termed hyperprogressive disease (HPD), has been reported in patients receiving checkpoint inhibitor therapy. HPD has been defined as a ≥ 2-fold increase in tumor growth rate (TGR) from baseline to first evaluation, by comparison with pre-treatment Alternate criteria describing rapid progression on CPI therapy have also been described. Whether HPD is unique to CPI remains unclear, as do associated predictive factors. We developed an alternative approach termed fast progression (FP), in order to study this phenomenon retrospectively in prior Phase III trials of CPI. In addition to CT-confirmed rapid early tumor growth, FP includes early death due to PD from cancer. Using these FP criteria, we analyzed data from the Phase III OAK study, demonstrating equivalent rates of FP with atezolizumab versus docetaxel. However more patients met criteria for FP by TGR increase with atezolizumab. Further, FP was not associated with previously reported predictive factors. This presentation will update those results as well as other new data regarding the HPD/FP phenomenon.

      Treatment Beyond Progression (TBP): Cancer immunotherapy may alter tumor biology such that treatment effects can extend beyond radiographic progression. This effect explains the discordance between relatively modest response rate/progression free survival and more impressive overall survival in multiple CPI trials in advanced NSCLC. Presumptive benefit of TBP with CPI therapy has been observed in multiple tumor types including melanoma, renal cancer and NSCLC, leading the FDA to call for randomized trials designed to study this phenomenon. We studied TBP in the Phase III OAK trial of atezolizumab versus docetaxel, and reported that post-PD efficacy was consistent with a positive benefit-risk profile of atezolizumab TBP in patients performing well clinically at the time of PD. INSIGNA, a recently activated joint ECOG-SWOG Phase III study, is the first prospective trial to include an arm evaluating TBP. This presentation will discuss the biologic rationale for TBP with CPIs and detail other recently published data.

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Author of

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    MA03 - Clinomics and Genomics (ID 119)

    • Event: WCLC 2019
    • Type: Mini Oral Session
    • Track: Advanced NSCLC
    • Presentations: 1
    • Now Available
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      MA03.06 - Efficacy Results of Selective AXL Inhibitor Bemcentinib with Pembrolizumab Following Chemotherapy in Patients with NSCLC (Now Available) (ID 2271)

      10:30 - 12:00  |  Author(s): Manuel Dómine

      • Abstract
      • Presentation
      • Slides

      Background

      The RTK AXL is implicated in epithelial-to-mesenchymal transition, negative regulation of anti-tumour immunity and resistance to multiple therapies including immune checkpoint inhibitors.

      Bemcentinib (BGB324) is a first-in-class, oral, highly selective and potent AXL inhibitor which has been demonstrated to enhance anti-PD1 therapy.

      Method

      This phase II trial (Cohort A, NCT03184571) enrolled 48 advanced lung adenocarcinoma patients with progression on or after no more than one prior line of platinum-based chemotherapy. Patients with EGFR/ALK mutations were included in this study and must have progressed on or after at least one standard targeted therapy. The primary endpoint was ORR according to RECIST v1.1. Additional endpoints included efficacy according to biomarker expression, DCR, PFS, OS, and safety. Tumour biopsies were analysed for PD-L1 expression (22C3 pharmDx), AXL by IHC, and infiltrating immune cells.

      Result

      As of April 2019, the trial was fully recruited: median age 65 (range 39-82) yrs, 61% male, 76% smokers or ex-smokers.

      At time of writing, a total of 210 treatment cycles had been completed by all patients. 17 patients were ongoing.

      17 of 32 biomarker-evaluable patients (53%) were PD-L1 negative, 13 (41%) had TPS 1-49%, and 2 (6%) had TPS >50%. Of 28 biomarker-evaluable patients, 14 (50%) expressed AXL on their tumours.

      Among patients who had at least 1 evaluable on-treatment scan: 5 responses were observed in 13 AXL positive patients (38%), and 7 in 30 patients with TPS 0-49% (23%). There were 10 responses observed among 34 evaluable patients overall (29%).

      In Stage 1, two of the 4 AXL positive responses are ongoing; mDoR is not mature in the AXL positive patients. mPFS was 5.9 mo in AXL positive patients (n=10, 3.0-NR) and 4.0 mo (95% CI 1.9-NR) overall (n=24). mOS was not mature.

      The most common TRAEs (occurring in >10% of patient in both stages) were transaminase increases (34%), asthenia/fatigue (30%), diarrhoea (26%), nausea (13%), anaemia (11%), decreased appetite (11%), and pruritus (11%). All cases of transaminase increase were reversible and resolved with concomitant administration of systemic corticosteroids and interruption of study treatments.

      Conclusion

      Patients had predominantly low or no PD-L1 expression; approximately half were AXL positive. The combination of bemcentinib and pembrolizumab was well tolerated and showed promising efficacy in previously treated IO-naïve NSCLC patients, particularly in those with AXL positive disease, including PD-L1 negative patients. Mature ORR for both stages, as well as 12-month OS for stage 1 will be presented at the meeting.

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    MA22 - Partnering with Patients to Understand Stigma, Disparities and Values Leading to Improved Lung Cancer Care (ID 154)

    • Event: WCLC 2019
    • Type: Mini Oral Session
    • Track: Advocacy
    • Presentations: 1
    • Now Available
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      MA22.05 - Assessment of Gender Differences in the Psychosocial and Economic Impact on Patients with Stage IV Non-Small Cell Lung Cancer (Now Available) (ID 718)

      15:45 - 17:15  |  Author(s): Manuel Dómine

      • Abstract
      • Presentation
      • Slides

      Background

      Incidence of lung cancer in women is rising overtime reporting evident gender-based differences in epidemiology, biology, and treatment outcome. However, little is known about gender-differences regarding psychological, economic and social aspects. The objectives of this prospective study are to evaluate the psychosocial and economic impact of metastatic non-small cell lung cancer (NSCLC), according to gender. Additionally, to assess the emotional burden and the economic impact of the disease on the primary caregiver from a gender perspective

      Method

      Multicenter, prospective, observational, study of two cohorts of patients with metastatic NSCLC (male and female) in Oncology departments of 20 Spanish hospitals. The following measurement tools were used: the APGAR questionnaire (family functionality: adaptability, partnership, growth, affection, and resolve), the Relationship impact scale, the DUKE-UNC scale (perceived socio-affective support), the patient and the caregiver economic impact scale and the Zarit scale (caregiver burden). All questionnaires were performed at the first visit, repeated 4 months later and following the first and second disease progression.

      Result

      Of the 333 pts included, 104 were females and 229 male, of whom 63% and 97%, respectively, were smokers/ex-smokers (p=0.0001). More women than men (85% vs 70%) had adenocarcinomas . The median overall survival was longer in women but did not reach statistical significance [17.1 vs 11.0 months, HR 0.732 (95% CI 0.534 to 1.005), p=0.0524]. Most families considered themselves functional (high score in APGAR questionnaire) with no changes in their partner relationship and social support was evaluated as optimal for majority of patients. Around a quarter of interviewed patients said their economic situation was a little worse after the lung cancer diagnosis, without remarkable differences by gender. 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. No remarkable differences by gender were found between the different variables across the study.

      Conclusion

      This study provides a preliminary insight into gender-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 gender perspective

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    OA13 - Ideal Approach to Lung Resection and Novel Perioperative Therapy (ID 146)

    • Event: WCLC 2019
    • Type: Oral Session
    • Track: Treatment of Early Stage/Localized Disease
    • Presentations: 1
    • Now Available
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      OA13.05 - NADIM Study: Updated Clinical Research and Outcomes (Now Available) (ID 1670)

      11:30 - 13:00  |  Author(s): Manuel Dómine

      • Abstract
      • Presentation
      • Slides

      Background

      Patients with stage IIIA (N2 or T4N0) are potentially curable but median overall survival is only around 15 months

      Method

      A Phase II, single-arm, open-label multicenter study of resectable stage IIIA N2-NSCLC in adult patients with CT plus IO as neoadjuvant treatment: 3 cycles of nivolumab (NV) 360 mg IV Q3W + paclitaxel 200 mg/m2 + carboplatin AUC 6 IV Q3W followed by adjuvant NV treatment for 1 year. After completing neoadjuvant therapy, all patients underwent tumor assessment prior to surgery. Surgery was performed during the 3rd or 4th week after day 21 of the 3rd neoadjuvant treatment cycle. The study aimed to recruit 46 patients. The primary endpoint was Progression-Free Survival (PFS) at 24 months. Efficacy was explored using objective pathologic response criteria. Here we present the final data on all study patients that underwent surgical assessment.

      Result

      At the time of submission, the 46 patients had been included. None of the patients were withdrawn from the study preoperatively due to progression or toxicity. 41 patients had undergone surgery and all tumors were deemed resectable with R0 resection in all cases. Intention to treat analysis shows 35 patients (85%; 95% CI, 71; 94%) achieved major pathologic response (MPR) of which 25 (71%; 95% CI, 54; 85%) were complete pathologic responses (CPR). Downstaging was seen in 38 (93%; 95% CI, 80; 98%) of cases. The median follow-up was 13.8 months (P25; P75: 11.7; 16.6 months) for both the whole series and resected patients, and 12 month PFS was 95.7% (95% CI, 84; 99%).

      Conclusion

      This is the first multicentric study to test CT-IO in the neoadjuvant setting in stage IIIA. Neoadjuvant CT-IO with nivolumab in resectable IIIA NSCLC yields a complete pathologic response rate that is higher than ever seen previously, together with a promising PFS which may translate into increased overall survival. EudraCT Number: 2016-003732-20. Clinical trial information: NCT 03081689.

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    OA14 - Update of Phase 3 Trials and the Role of HPD (ID 148)

    • Event: WCLC 2019
    • Type: Oral Session
    • Track: Immuno-oncology
    • Presentations: 1
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      OA14.04 - Five-Year Outcomes From the Randomized, Phase 3 Trials CheckMate 017/057: Nivolumab vs Docetaxel in Previously Treated NSCLC (ID 894)

      11:30 - 13:00  |  Author(s): Manuel Dómine

      • Abstract
      • Slides

      Background

      Historically, outcomes for advanced non-small cell lung cancer (NSCLC) have been poor, with 5-year survival rates < 5% with conventional chemotherapy. Nivolumab, a programmed death-1 (PD-1) inhibitor, was approved in 2015 for patients with previously treated advanced NSCLC based on two randomized phase 3 trials, CheckMate 017 (NCT01642004; squamous) and CheckMate 057 (NCT01673867; non-squamous), which demonstrated improved overall survival (OS) vs docetaxel. We report 5-year pooled efficacy and safety from these trials, representing the longest survival follow-up for randomized phase 3 trials of an immune checkpoint inhibitor in advanced NSCLC.

      Method

      Patients (N = 854; CheckMate 017/057 pooled) with advanced NSCLC, ECOG performance status (PS) ≤ 1, and progression during or after first-line platinum-based chemotherapy, were randomized 1:1 to nivolumab 3 mg/kg Q2W or docetaxel 75 mg/m2 Q3W until progression or unacceptable toxicity. After completion of the primary analyses, patients in the docetaxel arm no longer receiving benefit could cross over to receive nivolumab. OS was the primary endpoint for both studies.

      Result

      At 5-year follow-up, 50 nivolumab patients and 9 docetaxel patients were alive. Baseline characteristics of 5-year survivors in both arms were similar to the overall population and patients who survived < 1 year, except for a higher percentage of patients with ECOG PS 0 or tumor programmed death ligand-1 (PD-L1) expression ≥ 1% on nivolumab and ECOG PS 0 and Stage IIIB NSCLC on docetaxel. Nivolumab continued to show long-term OS and progression-free survival (PFS) benefit vs docetaxel with 5-year OS rates 13% vs 3% (HR, 0.68 [95% CI, 0.59–0.78]) and PFS rates 8% vs 0% (0.79 [0.68–0.92]). OS benefit with nivolumab vs docetaxel was observed across subgroups including patients with tumor PD-L1 expression < 1%, baseline liver and adrenal metastases, neutrophil-to-lymphocyte ratio < median, lactate dehydrogenase ≥ upper limit of normal or no baseline proton-pump inhibitor use. Among patients with an objective response to nivolumab (20%) or docetaxel (11%), 32% remained in response at 5 years vs none on docetaxel, with a median duration of response of 19.9 vs 5.6 months, respectively. Of the 5-year nivolumab vs docetaxel survivors, 36% vs 0% were on study drug, 20% vs 67% received subsequent immunotherapy (on or off study), and 10% vs 0% were off study drug, progression free, with no subsequent therapy. No new safety signals were observed with longer follow-up. Between 3 and 5 years’ follow-up, 8 of the 31 (26%) nivolumab-treated patients reported a treatment-related adverse event, 1 (3%) grade 3–4. The most common select adverse events (events with a potential immunological cause) were related to skin, in 4 (13%) patients, none of which were grade 3–4.

      Conclusion

      CheckMate 017 and 057 are the first phase 3 trials to report 5-year outcomes for a PD-1 inhibitor in previously treated advanced NSCLC, demonstrating a greater than 4-fold increase in 5-year OS rates with nivolumab (13%) over docetaxel (3%). Nivolumab remained well tolerated with no new safety signals.

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    P1.01 - Advanced NSCLC (ID 158)

    • Event: WCLC 2019
    • Type: Poster Viewing in the Exhibit Hall
    • Track: Advanced NSCLC
    • Presentations: 3
    • Moderators:
    • Coordinates: 9/08/2019, 09:45 - 18:00, Exhibit Hall
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      P1.01-111 - ATEZO-BRAIN, A Single-Arm Phase II Study of Atezolizumab Combined with Chemotherapy in Stage IV NSCLC Patients with Untreated Brain Metastases (ID 733)

      09:45 - 18:00  |  Author(s): Manuel Dómine

      • Abstract
      • Slides

      Background

      Brain metastases (BM) are a frequent complication in non-small cell lung cancer (NSCLC), have significant impact on quality of life and are associated with poor prognosis. Systemic therapies might be an alternative approach to whole brain radiotherapy (WBRT) to avoid cognitive-related adverse events. Immune checkpoint inhibitors (ICI) showed intracranial activity in advanced NSCLC patients with BM. However clinical data about efficacy and safety of immune checkpoint inhibitors in combination with chemotherapy in patients with untreated BM are limited and further research in this setting is needed. We hypothesize that addition of ICI to conventional platinum-based chemotherapy may increase intracranial tumor response and provide clinically relevant benefit in terms of PFS, OS and quality of life to the patients with asymptomatic and non-previously treated BM.

      Method

      This is an ongoing multicenter, open-label, single-arm phase 2 study (EUDRACT: 2017-005154-11) to evaluate the efficacy and safety of atezolizumab 1200 mg combined with 4-6 cycles of carboplatin AUC 5 and pemetrexed 500mg/m2 every 3 weeks followed by maintenance with atezolizumab 1200 mg plus pemetrexed 500mg/m2 every 3 weeks in stage IV non-squamous NSCLC patients with untreated synchronous BM. Patients should have multiple and measurable BM, adequate performance status and organic function, do not harbor EGFR or ALK genomic alterations, be treatment naïve and do not have any contraindication to receive immunotherapy. Exclusion criteria consist of active neurological symptoms, dexamethasone dose ≥ 4 mg QD, prior treatment with brain radiotherapy, presence of leptomeningeal carcinomatosis, spinal or hemorrhagic metastases in the central nervous system. Primary endpoints are progression-free survival (PFS) at 12 weeks according to RANO-BM and RECIST v1.1 criteria and safety based on CTCAE v4. Both primary endpoints will be assessed in 40 patients in 15 sites using a Bayesian approach. Patients will undergo tumor assessments by body CT scan and brain MRI at baseline every 6 weeks for the first 12 weeks and thereafter tumor assessments will be performed every 9 weeks until disease progression or loss of clinical benefit. Secondary endpoints: intracranial and systemic objective response rate and duration of response. Exploratory endpoints: to assess neurocognitive function and quality of life; to determine time to neurological deterioration and time to need of salvage brain radiotherapy. Enrollment started on August 2018 and currently 12 patients have been included in the study.

      Result

      Clinical trial in progress

      Conclusion

      Clinical trial in progress

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      P1.01-72 - A Phase II Study of Selective AXL Inhibitor Bemcentinib and Pembrolizumab in Patients with NSCLC Refractory to Anti-PD(L)1 (ID 1632)

      09:45 - 18:00  |  Author(s): Manuel Dómine

      • Abstract

      Background

      The RTK AXL is implicated in epithelial-to-mesenchymal transition, negative regulation of anti-tumour immunity and resistance to multiple therapies including immune checkpoint inhibitors.

      Bemcentinib (BGB324) is a first-in-class, oral, highly selective and potent AXL inhibitor which has been demonstrated to enhance anti-PD1 therapy.

      The combination of bemcentinib and pembrolizumab was well tolerated and showed promising efficacy in previously treated IO-naïve NSCLC patients (Cohort A, NCT03184571), particularly in those with AXL positive disease, including PD-L1 negative patients.

      The novel combination is now being assessed in patients refractory to anti-PD-(L)1 therapy, considering the emerging need in this population and AXL’s role as a mediator of resistance.

      Method

      This is an open-label, single-arm, 2-stage phase II study (Cohort B, NCT03184571) to evaluate the safety and efficacy of bemcentinib (200mg/d) in combination with pembrolizumab (200mg/q3wk) in patients post anti-PD-(L)1 therapy. The primary endpoint is overall response rate (ORR), and additional endpoints include efficacy by biomarker expression, duration of response (DoR), disease control rate (DCR), progression free survival (PFS), overall survival (OS), and safety. Clinical efficacy endpoints are based on tumour imaging evaluable by RECIST v1.1.

      Eligible patients received a maximum of 2 prior lines of therapy, with the most recent course having included a PD-(L)1 inhibitor. To be eligible, patients must have exhibited disease control (CR/PR/SD) for at least 6 months on prior PD-(L)1 inhibitor therapy with disease progression occurring within 12 weeks since last dose.

      Bemcentinib will be administered as a loading dose of 400mg on days 1, 2 and 3 followed by a dose of 200mg once daily. A fixed dose of 200 mg pembrolizumab will be given by intravenous infusion over 30 minutes every 3 weeks. Bemcentinib and pembrolizumab will be given until disease progression, unacceptable dose toxicity, or for a maximum of 35 cycles.

      Tumour specimens will be analysed for PD-L1 expression (22C3 pharmDx), AXL by IHC, and infiltrating immune cells.

      The pre-specified efficacy threshold for continuation into the second stage is 1 objective response among the first 13 patients, at which point up to a further 16 patients may be evaluated, for a total of 29 patients.

      Result

      Section not applicable

      Conclusion

      Section not applicable

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      P1.01-93 - Metastases Sites as a Prognostic Factor in a Real-World Multicenter Cohort Study of Spanish ALK-Positive NSCLC Patients (p) (ID 1377)

      09:45 - 18:00  |  Author(s): Manuel Dómine

      • Abstract

      Background

      ALK gene rearrangements are detected in 3-7% of Non-Small-Cell-Lung-Cancer (NSCLC) p. EML4-ALK translocation was first identified as an oncogene in NSCLC p in 2007. To date, published real-world data on the prognostic factors of patients with ALK-positive advanced NSCLC in Spain are limited. We aim to evaluate the effect of number of metastases (M1) organs on overall survival (OS) in a multicenter cohort of Spanish ALK-positive NSCLC p diagnosed between 2008 and 2017.

      Method

      We included p with stage IV at diagnosis since 2011 to April 2018. OS (months [m]) was estimated with the Kaplan-Meier method. Survival curves were compared between groups of p using the log-rank test. Hazard risk (HR) to death was estimated with multivariable Cox model, adjusted by site of metastases, gender, age and first line type of treatment.

      Result

      Out of the 163 p in the cohort a total of 98 p were included, with a median follow-up of 28.6 m and 45 deaths reported. Characteristics at diagnosis were median age 58 years, female 46.9%, never-smokers 59.2%, 50% with comorbidities, PS by ECOG 0-1 93%, 58.2% lung M1, 45.9% central nervous system M1, 42.9% bone M1, 22.4% liver M1 and 29.6% pleural M1.

      54.3% p and 89.4% p were treated with ALK inhibitors as first line and second line respectively. The median OS was 34.4 months, being 46.9 months in p treated with ALK inhibitors and 38.8 months in p treated with chemotherapy as first line (p= 0.9).

      There were 72 p who presented M1 in more than one organ and 26 p in a single organ. The risk of death increased with greater number of organs involved at diagnosis (HR= 3.0, p=.016), and presenting liver M1 at diagnosis (HR=2.2, p=.046, with OS of 19.1 m), compared to p single site involvement (OS: 45.4 m).

      Conclusion

      OS was worse with increased metastatic sites involved at diagnosis in p with ALK positive NSCLC, being liver M1 associated with the highest risk of mortality. Brain metastases at diagnosis were not a prognostic factor for OS in our series.

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    P1.03 - Biology (ID 161)

    • Event: WCLC 2019
    • Type: Poster Viewing in the Exhibit Hall
    • Track: Biology
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/08/2019, 09:45 - 18:00, Exhibit Hall
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      P1.03-15 - Non-Invasive Detection of Secondary Resistance Mutations in ALK-Positive NSCLC Patients by Next-Generation Sequencing (ID 1658)

      09:45 - 18:00  |  Author(s): Manuel Dómine

      • Abstract
      • Slides

      Background

      ALK inhibitors have led to important improvements in ALK-positive non-small cell lung cancer (NSCLC) patient’s survival and quality of life. However, despite the good responses, resistance mutations inevitably emerge. Several resistance mutations in ALK domain have been describe. Remarkably different mutations can confer different sensitivities to different ALK inhibitors. However, 2nd and 3rd line treatment is often prescribe empirically without knowing the molecular mechanism underlying treatment failure.

      Method

      21 samples from ALK-positive NSCLC patients were collected at disease progression. Circulating Nucleic Acids were isolated from platelets, exosomes and plasma. Libraries were prepared using 20ng of template and Oncomine™ Pan-Cancer Cell-Free Assay. Samples were sequenced on an Ion GeneStudio S5 Plus System. Sequencing data was first analyzed using Torrent Suite software. Subsequently variant calling, annotation and filtering was performed on the Ion Reporter (v5.10) platform using the Oncomine TagSeq Pan-Cancer Liquid Biopsy w2.1 workflow.

      Result

      In 14 (67%) patients a somatic mutation was identified in the plasma sample collected at disease progression. The average number of mutations detected per sample was 2.6. Noteworthy, 14 mutations were found in oncogenes that have been previously associated with ALK inhibitors resistance (5 mutations in ALK locus, 4 mutations in PIK3CA, 1 mutation in EGFR, 1 mutation in KIT, 1 mutation in KRAS, 1 mutation in MTOR and 1 mutation in MYC). The rest of mutations (N=21) were found in TP53 gene. Secondary resistance mutation in ALK locus occurred in 24% of the cases. Specifically, p.G1269A (N=2), p.G1202E (N=1), p.R1275Q (N=1) mutations were found in ALK-positive NSCLC who had progressed on crizotinib and p.G1202R mutation was found in 1 ALK-positive NSCLC who had progressed on ceritinib.

      Conclusion

      Secondary ALK-TKI resistance mutations could be detected using liquid biopsies in a high proportion of patients. Non-invasive molecular profiling of samples collected at disease progression is feasible being useful for further treatment selection in ALK-positive NSCLC patients.

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    P2.03 - Biology (ID 162)

    • Event: WCLC 2019
    • Type: Poster Viewing in the Exhibit Hall
    • Track: Biology
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/09/2019, 10:15 - 18:15, Exhibit Hall
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      P2.03-33 - ctDNA Levels Significantly Predicts Survival in NSCLC Patients with an EGFR Activating Mutation (ID 2016)

      10:15 - 18:15  |  Author(s): Manuel Dómine

      • Abstract

      Background

      Circulating tumor DNA (ctDNA) have been shown to be useful for non-invasive biomarker testing in non-small cell lung cancer (NSCLC). In addition, there is growing evidence supporting that ctDNA levels can be useful for tumor response to treatment monitoring. Nevertheless, data from large prospective clinical longitudinal studies still limited.

      Method

      300 plasma samples from 100 advanced NSCLC patients, with tumors harboring an EGFR activating mutation and treated with a first line tyrosine Kinase inhibitor were analyzed. Samples were collected before the start of treatment, at first follow up evaluation, at 7 month and at disease progression. ctDNA was analyzed by dPCR.

      Result

      Median follow up was 11.3 months. There were not significant differences in progression free survival (PFS) or overall survival (OS) according to treatment (erlotinib, afatinib or gefitinib). Patients harboring a deletion in exon 19 or a mutation in exon 21 exhibited better survival than those with an insertion in exon 20 (P<0.001). dPCR detected EGFR sensitizing mutation in 77% of the pre-treatment samples. ctDNA levels before the start of the treatment did not significantly predict survival, although a tendency was observed, with patients with high levels of ctDNA showing poorer outcome. On the contrary, patients in which the EGFR sensitizing mutation was undetectable at first follow up had a markedly better PFS and OS (HR=2.7; 95IC= 1.4-5.5 and HR= 5.5 95IC: 1.8-17 respectively). In the same way, patients in which the EGFR sensitizing mutation remained negative at 7months had a significantly increased PFS (HR: 2.8; 95IC: 1.2-6.6). None of the patients with undetectable levels at 7 months has deceased.

      Conclusion

      ctDNA levels is of prognostic significance in EGFR positive NSCLC patients with advance disease and can be useful to monitor treatment outcome

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    P2.04 - Immuno-oncology (ID 167)

    • Event: WCLC 2019
    • Type: Poster Viewing in the Exhibit Hall
    • Track: Immuno-oncology
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/09/2019, 10:15 - 18:15, Exhibit Hall
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      P2.04-10 - Biomarkers of Pathological Response on Neo-Adjuvant Chemo-Immunotherapy Treatment for Resectable Stage IIIA NSCLC Patients (ID 1466)

      10:15 - 18:15  |  Author(s): Manuel Dómine

      • Abstract
      • Slides

      Background

      PD1/PDL1 treatments have become the main therapy in advanced stages of NSCLC due to its significant increase in overall survival (OS), but recently, combination with chemotherapy in locally advanced stages is showing promising results. Many studies have described peripheral blood immune cells parameters as biomarkers of response to immunotherapy. In our study, we described the effect of neo-adjuvant chemo-immunotherapy treatment in Complete Blood Count (CBC) and Peripheral Blood Mononuclear Cells (PBMCs) phenotype, as well as, the association of these parameters with the degree of pathological response.

      Method

      Immune cell populations of 46 resectable stage IIIA NSCLC patients treated with neo-adjuvant chemo-immunotherapy from NADIM clinical trial were analysed. Samples were extracted before initiating the neo-adjuvant treatment with nivolumab plus carboplatin and at the third cycle before patients underwent surgery. We classified patients in 3 subgroups of pathological response assessed in the resection specimen: complete response (pCR), major response (<10% viable tumour) and incomplete response (>10% viable tumour, pIR). Wilcoxon and Mann-Whitney U statistic test were used to evaluate differences between pre and post treatment and between pathological responses groups respectively.

      Result

      From 46 patients, 5 patients did not undergo surgery, so they were excluded from the analysis. Absolute numbers of Leucocytes, Eosinophil, Monocytes, Neutrophils, Haemoglobin and Platelets from hemograms were significantly reduced after neo-adjuvant treatment. However, no changes were observed for Lymphocytes, Basophils, LDH levels or the Lung Immune Prognostic Index (LIPI). Additionally, post-treatment Neutrophil-to-Lymphocyte (NLR), Myeloid-to-Lymphoid lineage (M:L) and Platelets-to-Lymphocytes (PLR) ratios were decreased. Remarkably, from all the CBC absolute numbers and ratios, only PLR variation showed differences between pCR and pIR.

      On the other hand, percentages of PBMCs (T cells, B cells, NK cells and macrophages) did not vary after neo-adjuvant treatment, however activation of CD4 T cells and NK cells as well as PD-1 receptor expression on immune cells were downregulated after neo-adjuvant chemo-immunotherapy. Interestingly, these variations correlate with pCR.

      Conclusion

      In our study, PLR, PD-1 expression, CD4 T cells and NK cells activation are predictive biomarkers of response to treatment. Thus, a higher decrease on PLR post neo-adjuvant treatment is associated to pCR. Moreover, a decrease of PD-1 expression in CD4, CD8 and NK cells, as well as, a reduction of CD4 T cells and NK cells activation after neo-adjuvant treatment, are associated to pCR.

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    P2.05 - Interventional Diagnostic/Pulmonology (ID 168)

    • Event: WCLC 2019
    • Type: Poster Viewing in the Exhibit Hall
    • Track: Interventional Diagnostics/Pulmonology
    • Presentations: 2
    • Moderators:
    • Coordinates: 9/09/2019, 10:15 - 18:15, Exhibit Hall
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      P2.05-10 - Liquid Biopsy: Association Between the Burden of Disease in Patients with EGFR-Mutated NSCLC and the Frequency of Its Detection in Blood (ID 2384)

      10:15 - 18:15  |  Author(s): Manuel Dómine

      • Abstract
      • Slides

      Background

      In the management of patient’s whit non small cell lung cancer (NSCLC) with EGFR mutations after progression to first and second generation tyrosine kinasa inhibitors (TKI), the mechanism of resistance is very important. Our objective is to analyse the appearance kinetics of the T790M by means of digital PCR techniques in liquid biopsy.

      Method

      We conducted a multicenter study with 100 patients with EGFR-mutated NSCLC, treated with first-line TKI therapy. We analyze the ctDNA by dPCR before the start of treatment, at first follow up evaluation, at 6 months and at disease progression.

      Result

      We included a total of 100 patients from July 2016 to December of 2017. Seven patients with Exon 20 insertion in EGFR were excluded (final sample 93). The median of follow-up was 12 months. There were not significant differences in progression free survival (PFS) or overall survival (OS) according to treatment (erlotinib, gefitinib or afatinib). dPCR detected EGFR sensitizing mutation in 77% of the pre-treatment samples. Of these cases, EGFR sensitizing mutation was detected in 75% of the patients with stage IVA and 85% in stage IVB respectively, p=0,075. The resistance mutation p.T790M was detected in 52% of the samples collected at disease progression. The probability to detect the resistance mutation p.T790M by liquid biopsy, is greater if the pre-treatment sample was positive for EGFR sensitizing mutation (11% vs 62%) p 0,009. In cases with progression of the disease the percent of detection of p.T790M was 52% and 54% in patients with Exon 19 deletion and L858R mutation respectively. The OS in patients with progression of the disease and p.T790M negative was 85% at 12 months (95%CI: 60%-94%) and 75% with p.T790M positive (95%CI: 49%-88%), p=0,01.

      Conclusion

      The burden of disease in patients with NSCLC mutated with EGFR is related to the appearance of sensitivity and resistance mutations in liquid biopsy. The probability to detect the resistance mutation p.T790M in blood, is greater if the pre-treatment sample was positive for EGFR sensitizing mutation.

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      P2.05-12 - Analysis of Biomarkers in Lung Cancer in Spain (ID 854)

      10:15 - 18:15  |  Author(s): Manuel Dómine

      • Abstract

      Background

      The analysis of biomarkers in lung cancer (LC) is currently one of the most important care needs, given the importance of their presence in the selection of specific treatments. Our objective was to know the implementation degree of these tests in a large cohort of patients in Spain using the Thoracic Tumor Registry (TTR) of the Grupo Español de Cáncer de Pulmón (Spanish Lung Cancer Group).

      Method

      The TTR is an observational cohort multicenter study of the LC in Spain. Information on patients (p) enrolled from August 2016 to December 2018. The study is conducted according to the Declaration of Helsinki and approved by the institutional review board of each participating institute. The registry was approved by the Spanish Drug Agency as a non-post-authorization, non-interventional study.

      Result

      A total of 7,872 patients from 58 Spanish sites were enrolled. Analysis of molecular markers considering all the LC stages: A molecular test, the most frequent being the EGFR test, was performed in 4,456 patients (67.5%). The proportion of biomarker evaluation has varied over time, ranging from 57.9% prior to 2012 up to 73.7% in 2017.

      Molecular markers in patients with stage IV. Three thousand four hundred forty-six (3,446) patients (52.2%) had a stage IV on diagnosis. The molecular assessment of some biomarkers reached 81.4% of all the patients, there being differences between Regional Communities in regard to the molecular tests made.

      There was performed some biomarker test in 92% of the 2570 patients with stage IV and adenocarcinoma histology. The analysis of ALK was tested in 79% of the patients, this being in 40% only 2 years ago. ROS was studied in 20% of the cases and EGFR in 92%.

      Conclusion

      Although no national plan exists for molecular biomarker analysis in LC in Spain, the implementation of the biomarkers analysis in all the hospitals that contribute to the TTR is high, as close to the maximum as possible. The increase in the ALK analysis in the last period is relevant. As regional differences exist, it would be of interest to go in depth to study its cause

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    P2.10 - Prevention and Tobacco Control (ID 176)

    • Event: WCLC 2019
    • Type: Poster Viewing in the Exhibit Hall
    • Track: Prevention and Tobacco Control
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/09/2019, 10:15 - 18:15, Exhibit Hall
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      P2.10-02 - Smoking Habit in Lung Cancer in Spain   (ID 732)

      10:15 - 18:15  |  Author(s): Manuel Dómine

      • Abstract
      • Slides

      Background

      Tobacco is the leading cause of lung cancer. The fight against the smoking habit is essential and should be continuous, to detect the national situation that makes it possible to design health care policies against this consumption. To do so, the Grupo Español de Cáncer de Pulmón (Spanish Lung Cancer Group) made this analysis within the context of the Thoracic Tumor Registry (TTR).

      Method

      The TTR is an observational cohort multicenter study in Spain. The study is conducted according to the Declaration of Helsinki and approved by the institutional review board of each participating site. The registry was approved by the Spanish Drug Agency, as a non-post-authorization, non-interventional study.

      Result

      We collected data from 6,600 patients diagnosed of lung cancer from 58 different Spanish hospital sites.

      A total of 3,039 patients were former smokers (46%), 2,611 were active smokers (39%) and only 866 (12%) patients stated to be non-smokers; the status in 2% is unknown. If we make a comparison by gender regarding the presence of this habit, large differences (p-valor < 0.001) are observed, with a greater number of non-smokers in women (37 % vs. 4.5% in males), while the percentage of former smokers is much higher in the males (53.4% vs. 27.9% in women) and a minor difference in active smokers (42.1% vs. 34.4% in women).

      Significant differences were observed in the study on the distribution of the smoking habit by gender and year of diagnosis. An increase is also observed in the last two years regarding the percentage of patients who were active smoked, both for the total population as well as for each one of the two genders separately. The increase is greater among the women and, also, the number of women who are active smokers is greater in recent years.

      Mean age of onset of the smoking habit is 18.2 years. Significant differences are observed between both genders (p-valor < 0.001), with a mean age of initiation of 17.9 years in the men (95%CI 17.6-18.2 years) and 19.2 years in the women (95%CI 18.5-19.8 years). Significant differences between Regional Communities were also found in the mean age at onset of the habit, with much lower levels in the Valencian Community (16.6 years) or Navarra (16.9 years) regarding other communities, such as the Region of Murcia (22.9 years) or the Balearic Islands (21.6 years)

      Conclusion

      Lung cancer in Spain is associated to tobacco consumption in 85% of the cases diagnosed. Consumption has shown an increase in both genders in recent years and is especially rapid and worrisome in women. Anti-smoking campaigns should be reactivated and the causes of the regional differences analyzed in depth

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