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Ana Zimmer Gelatti Gelatti



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    EP1.16 - Treatment in the Real World - Support, Survivorship, Systems Research (ID 206)

    • Event: WCLC 2019
    • Type: E-Poster Viewing in the Exhibit Hall
    • Track: Treatment in the Real World - Support, Survivorship, Systems Research
    • Presentations: 1
    • Now Available
    • Moderators:
    • Coordinates: 9/08/2019, 08:00 - 18:00, Exhibit Hall
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      EP1.16-39 - Prospective Epidemiological Study of Metastatic Non-Small Cell Lung Cancer (NSCLC) in Latin America – LATINO Lung (LACOG 0116) (Now Available) (ID 1405)

      08:00 - 18:00  |  Presenting Author(s): Ana Zimmer Gelatti Gelatti

      • Abstract
      • Slides

      Background

      Non-small cell lung carcinoma (NSCLC) is the main cause of cancer-related death in Latin America. Nonetheless, there is insufficient information regarding its epidemiology, treatment and outcomes in the region. The goals of this study are to describe disease characteristics, treatment patterns and survival for advanced NSCLC in Latin America.

      Method

      LACOG 0116 LATINO Lung is a prospective cohort study aiming to include approximately 800 patients with advanced stage NSCLC (stage III/IV at diagnosis or distant relapse of early-stage disease) from 24 sites in Brazil, Argentina, Mexico, Colombia and Chile. All consecutive newly diagnosed patients seen at each site will be invited to participate. Data on socioeconomic and demographic characteristics, medical/oncologic history and clinical-pathological characteristics will be collected at baseline. Thereafter, patients will be followed every 6 months for 3 years in order to gather information regarding treatment patterns and sequencing, reasons for treatment discontinuation, response to treatment, disease progression and overall survival. Data will be collected during medical visits or telephone calls and by medical charts review. Primary endpoint is to estimate the overall survival. Descriptive analysis of treatments and outcomes are planned. Multivariable regression methods will be applied to assess possible independent prognostic or predictive factors.

      Result

      As of April 3rd, 2019, 107 patients have been included, all of them within 16 sites in Brazil. Currently, there are 2 sites from Argentina, 2 from Mexico, 3 from Colombia and 1 from Chile awaiting regulatory approval to begin enrollment. Recruitment is planned to last until December 2019, when the estimated sample size will be achieved.figure1.png

      Conclusion

      LACOG 0116 LATINO Lung is the first Latin American lung cancer prospective cohort study that will generate real-world data on NSCLC. The study may identify gaps and inequities in a diverse population of NSCLC in Latin America and consequently raise the need for improvement and individualized approach of lung cancer care in the region.

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    IBS21 - Combating Toxicity of IO-Chemotherapy Combinations (Ticketed Session) (ID 52)

    • Event: WCLC 2019
    • Type: Interactive Breakfast Session
    • Track: Treatment in the Real World - Support, Survivorship, Systems Research
    • Presentations: 1
    • Now Available
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      IBS21.01 - Enhanced Toxicity of IO with Concurrent Chemotherapy (Now Available) (ID 3379)

      07:00 - 08:00  |  Author(s): Ana Zimmer Gelatti Gelatti

      • Abstract
      • Presentation
      • Slides

      Abstract

      Of the more than 18 million new cancer cases seen worldwide in 2018, approximately 2 million (11%) were lung cancer. More importantly, 1.7 million deaths were seen due to the disease, representing 18% of all cancer related deaths. Global age standardized incidence/mortality rates (22.5/18.6) clearly indicate that today, most patients diagnosed with lung cancer succumb to the disease. With the increasing incidence and mortality seen particularly in developing countries lung cancer is one of the most important global public health current challenges.

      With recent advances seen over the last couple of decades, therapeutic decisions for NSCLC are based not only on disease stage, comorbidities, performance status and histology, but also should consider the mutational and immunological profile of the tumor and obviously each patient’s preferences as well.

      Until recently, for tumors without any identifiable molecular driver, platinum doublets were the standard treatment for advanced disease. In these patients, despite extensive studies trying to improve current results, “old” targeted agents (bevacizumab, cetuximab) added to standard chemotherapy regimens suggested very modest if any benefit at all. Immune check-point inhibitors introduced over the last few years, have revolutionized our treatment approach and stand to change the natural history of the disease.

      As single agents, immune check-point inhibitors are effective in a proportion of patients, however a large majority either do not respond or develop resistance. On the basis of still very limited knowledge of primary and secondary mechanisms of resistance, combination approaches with other standard therapies and other immunotherapy strategies have been explored. Unfortunately, in most cases, lack of specific information on the molecular interactions between these therapies remains an important barrier. Albeit basically empirically designed, combinations of PD1/PDL1 inhibitors with standard platinum doublets have demonstrated benefits and are apparently increasing the proportion of patients benefiting from single agent immunotherapies.

      For many years, chemotherapy has been considered as an immunosuppressant. This is clearly the case in some situations depending on the specific agent and the dose being administered. However, in preclinical models, chemotherapy has shown the potential to increase the immunogenicity of cancer cells increasing the release of tumor antigens, attracting DCs, downregulating PDL1/PDL2 in DCs, enhancing tumor cell recognition and lysis and at the same decreasing microenvironment immunosuppressive factors. With the current need of designing rational combinations, it becomes extremely important to recognize that different chemotherapeutic agents have different interactions with the immune system and that addressing these differences is mandatory to achieve the best possible results.

      So, with these reasoning, it is fair to say that, among the multitude of specific cytotoxic effects of the different available chemotherapeutic agents and regimens it can be hypothesized that the combination of chemotherapy and IO may enhance immune effects.

      The combination of chemotherapy and immunotherapy (CIT) has attracted attention of clinicians and researchers and has been investigated in multiple clinical trials. Improved efficacy has been seen with these combinations but as expected, toxicity issues have also been observed. In this particular setting, we will address the intriguing question of how combining chemotherapy and immunotherapy may interfere in chemotherapy related adverse events.

      A recent metanalysis explored this particular issue and collected trial information from 6 randomized studies in the first line treatment of NSCLC patients. Compared with standard chemotherapy, the combination of PD-1/PD-L1 inhibitors with chemotherapy is statistically associated with a 38% reduction in the risk of disease progression, a 32% reduction in the risk of death and increases 1.6 times the probability of achieving an objective response. These results are achieved at the expense of increased treatment-related adverse events.

      In particular, the combination was associated with an increased risk of developing grade 3 or worse severity adverse events, an increase in treatment related drug discontinuations and an increase in serious adverse events. However, the number of treatment related deaths was similar with both treatments.

      Importantly, we need to consider that these data, as most of the information we have available form randomized phase III trials reflect the effects in the limited patient populations included in these trials and do not apply to special populations such as elderly patients, patients with autoimmune diseases, patients with worse ECOG PS (>2), patients with HIV or with hepatitis B/C and patients on chronic use of steroids. RWD and further trials specifically exploring these groups of patients will be essential to better inform the optimal management of these cases.

      Nevertheless, recent presented information on the long-term benefits of mainly single agent immunotherapy with a proportion of patients with advanced NSCLC surviving in excess of 3-5 years, raises the issue of a clear impact on the natural history of the disease. This has been previously shown in diseases that explored immunotherapy earlier such as melanoma for example. Further research should try to rationally approach combination regimens and to specifically select patient populations that could derive more benefit. At the same time this will help defining and improving the risk benefit relationship of these regimens.

      References:

      Galluzzi L, et. al. Immunological Effects of Conventional Chemotherapy and Targeted Anticancer Agents. Cancer Cell 28, December 14, 2015.

      Hato SV, et al. Molecular Pathways: The Immunogenic Effects of Platinum-Based Chemotherapeutics Clin Cancer Res; 20(11); 2831–7, 2014

      Zhou Y, et al. Immune-checkpoint inhibitor plus chemotherapy versus conventional chemotherapy for first-line treatment in advanced non-small cell lung carcinoma: a systematic review and meta-analysis. Journal for Immuno Therapy of Cancer (2018) 6:155.

      Kanwal B, et al. Immunotherapy in Advanced Non-small Cell Lung Cancer Patients: Ushering Chemotherapy Through the Checkpoint Inhibitors?Cureus. 2018 Sep; 10(9): e3254.

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    MA11 - Immunotherapy in Special Populations and Predictive Markers (ID 135)

    • Event: WCLC 2019
    • Type: Mini Oral Session
    • Track: Immuno-oncology
    • Presentations: 1
    • Now Available
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      MA11.12 - Discussant - MA11.09, MA11.10, MA11.11 (Now Available) (ID 3766)

      14:00 - 15:30  |  Presenting Author(s): Ana Zimmer Gelatti Gelatti

      • Abstract
      • Presentation
      • Slides

      Abstract not provided

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    P1.09 - Pathology (ID 173)

    • Event: WCLC 2019
    • Type: Poster Viewing in the Exhibit Hall
    • Track: Pathology
    • Presentations: 1
    • Now Available
    • Moderators:
    • Coordinates: 9/08/2019, 09:45 - 18:00, Exhibit Hall
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      P1.09-02 - Comprehensive Genomic Profiling of Non-Small Cell Lung Cancer in Brazil (GBOT 0118/LACOG 0418) (Now Available) (ID 2048)

      09:45 - 18:00  |  Author(s): Ana Zimmer Gelatti Gelatti

      • Abstract
      • Slides

      Background

      Lung cancer is the leading cause of cancer-related morbidity and mortality worldwide. Cancer driver mutations have been examined extensively and are the basis for modern precision therapy. The access of genomic tests in Brazil and, therefore, the prevalence of driver mutations of NSCLC in the country is not well described. The objective of this study is to carry out an epidemiological analysis of the somatic genetic profile of Brazilian NSCLC samples tested with FoundationOne®.

      Method

      GBOT 0118/LACOG 0418 is a retrospective cross-sectional study with patients diagnosed with NSCLC in Brazil and who performed comprehensive genomic profiling (CGP) using FoundationOne® or FoundationACT®. Raw data containing anonymous clinical-pathological characteristics and the results of CGP was analyzed. We described the molecular profile of patients using descriptive statistics. Categorical variables are presented as frequency and compared using the Chi-square test.

      Result

      We obtained a total of 513 CGP results, 457 (89.0%) from Foundation One® and 56 (10.9%) from FoundationACT®. Adenocarcinoma was the most common histological subtype (83.8%) followed by NSCLC NOS (16.1%). Median age at testing date was 64 years, and 51.27% were male. EGFR activating mutations were detected in 23.39% patients, ALK rearrangements in 5.65%, ROS1 rearrangements in 2.34%, RET alterations in 2.53%, BRAF mutations in 5.46%, KRAS mutations in 25,15% and NTRK fusions in 0,58% . Tumor mutational burden (TMB) analysis was available for 80.51% of samples tested and was measured in mutation per megabase. TMB were divided into three groups based on the Foundation Medicine reports: low (1-5 mutations/mb), intermediate (6-19 mutations/mb) and high (≥ 20 mutations/mb). The of tumors had low (42.69%) or intermediate (32.36%) TMB, and only 5.46% had high TMB.

      Table 1. Frequency of somatic genetic alterations in tumors tested with FoundationOne® and availability of targeted therapies in Brazil.

      GENE

      Frequency in NSCLC (%)

      Availability in Brazil

      EGFR

      23.39

      Approved

      ALK

      5.65

      Approved

      ROS1

      2.43

      Approved

      BRAF

      5.46

      Approved

      KRAS

      25.15

      No drugs available

      RET

      2,53

      Drugs available but not approved

      NTRK

      0,58

      Drugs available but not approved

      Conclusion

      This is the most comprehensive study describing CGP of NSCLC in Brazil using FoundationOne® or ACT. Our study shows rates of EGFR mutations and ALK rearrangements similar to those previously described. The knowledge of the molecular patterns of NSCLC in Brazil may help to improve health policies and access to targeted agents in the country.

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