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Luis Corrales
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EP1.04 - Immuno-oncology (ID 194)
- Event: WCLC 2019
- Type: E-Poster Viewing in the Exhibit Hall
- Track: Immuno-oncology
- Presentations: 3
- Now Available
- Moderators:
- Coordinates: 9/08/2019, 08:00 - 18:00, Exhibit Hall
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EP1.04-44 - Exploration of Factors Relating to Paradoxical Immune Response in Patients Treated with Immune Checkpoint Inhibitors for NSCLC (Now Available) (ID 2634)
08:00 - 18:00 | Author(s): Luis Corrales
- Abstract
Background
Although the introduction of immune checkpoint inhibitors (ICIs) has yielded substantial benefits in terms of survival in the treatment of Non-Small Cell Lung Cancer (NSCLC), the possibility of activation of dormant autoimmune diseases or onset of immune mediated toxicities is a reality. The objective of this study was to explore intrinsic immunological factors associated with poor outcomes.
Method
In a retrospective cohort study of 48 patients, without any prior medical history of autoimmunity, treated for advanced/metastatic NSCLC with ICI´s were assessed. Determination of HLA-A*02011 as well as acute phase reactants and antiphospholipid antibodies was performed. Additionally, evaluation of survival in a time to event manner was conducted using the Kaplan Meier method and Cox regressions
Result
Median follow-up was 27.3 months, of the included patients 26 were male (54%) with a median age of 62 years old and there were no individuals with and ECOG performance score >1. Median overall survival (OS) was reached at 22.47 months. When analyzing the presence of the HLA-A*02011 serotype, 6 patients tested positive (12.5%). Additionally, all presented with borderline or abnormal B2glycoprotein IgM and IgG, 2Bmicroglubulin and elevated C reactive protein. Four patients (66%) experienced reactive lymphadenopathy during treatment and all suffered some form of venous thromboembolism. When analyzing OS, this group of patients had a significantly worse outcome (6.53 vs 22.47 months, HR= 4.47, [95%CI 1.47 – 13.61], p<0.001) compared with their counterparts. Overall response rate for the whole was superior for the HLA-A*02011 positive patients achieving 41.4% and 33%, p<0.001, respectively.
Conclusion
The presence of the HLA-A*02011 could potentially predispose to a paradoxical and pathological activation of the immune system without offering any benefit in terms of tumor control. Larger studies validating these findings are warranted.
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EP1.04-45 - Relevance of Antibiotic Use on Clinical Activity of Immune Checkpoint Inhibitors in Hispanic Patients with Advanced NSCLC (CLICAP-ABs) (Now Available) (ID 2674)
08:00 - 18:00 | Author(s): Luis Corrales
- Abstract
Background
The composition of gut microbiota affects antitumor immune responses, as well as preclinical and clinical outcomes following immune checkpoint inhibitors (ICI) in cancer. Antibiotics (ATB) alter gut microbiota diversity and composition leading to dysbiosis, which may influence the effectiveness of ICI.
Method
We examined patients with advanced non-small-cell lung cancer (NSCLC) treated with anti-programmed cell death ligand-1 mAb monotherapy alone or in combination in three different countries of Latin America. Those receiving ATB within 30 days of beginning ICI were compared with those who did not. Objective response, progression free survival (PFS) and overall survival (OS) were assessed.
Result
18 of 140 (13%) NSCLC patients received ATB. The most commonly used ATB were b-lactam or quinolones for pneumonia or urinary tract infections. In NSCLC patients, ATB was associated with 4 cases of primary PD (28.6% versus 31.5%, P=0.818), non-significant decreased PFS (median 2.66 versus 1.94 months, HR 1.63, [95% CI 0.71-3.72], P=0.247) and significantly deleterious OS (median 12.42 versus 2.04 months, HR 2.3, [95% CI 1.08-4.95], P=0.03). In multivariate analyses, the impact of ATB remained significant for OS.
Conclusion
ATB were associated with reduced clinical benefit from ICI in Hispanic patients with NSCLC. Modulation of ATB-related dysbiosis and gut microbiota composition may be a strategy to improve clinical outcomes with ICI.
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EP1.04-46 - Immunotherapy at Any Line Improves Survival in Hispanic Patients with Advanced Metastatic NSCLC Compared to Chemotherapy (Quijote-CLICaP) (Now Available) (ID 2776)
08:00 - 18:00 | Author(s): Luis Corrales
- Abstract
Background
Immunotherapy for NSCLMC offers a significant advantage to chemotherapy in selected cases. This benefit starts to disapear as the patients start two progress and requiere change in medication or even chemotherapy. The objective of this study was to compare survival outcomes of patients with advanced or metastatic NSCLC who received immunotherapy at first, second or beyond versus matched patients receiving standard chemotherapy.
Method
A retrospective multicenter international cohort study of 296 patients with unresectable/ metastatic NSCLC treated with immunotherapy either as first, second, third or fourth line was conducted. A matched comparison with a historical cohort of first line chemotherapy was conducted.
Result
Median age was 64 years (Range 34-90) and 40.2% were female patients. 91.2% of patients had an ECOG performance score ≤ 1. Immunotherapy as first line was given to 39 patients (13.7%), second line to 140 (48.8%), and as third line and beyond to 108 (37.6%). Median overall survival was 19.9 months (95% CI 14.5-22.7 months) and progression-free survival was 3.73 months (95% CI 2.8-4.2). Factors associated with increased survival included treatment as first-line (p < 0.001), type of response (p < 0.001) and PD-L1 status (p = 0.0039). Compared with the historical cohort, immunotherapy proved to be superior in terms of OS (p= 0.05) but not PFS (p= 0.2).
Conclusion
Patients who receive immune checkpoint inhibitors as part of their treatment for NSCLC have better OS compared with matched patients treated with standard chemotherapy, regardless of treatment line.
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EP1.15 - Thymoma/Other Thoracic Malignancies (ID 205)
- Event: WCLC 2019
- Type: E-Poster Viewing in the Exhibit Hall
- Track: Thymoma/Other Thoracic Malignancies
- Presentations: 2
- Now Available
- Moderators:
- Coordinates: 9/08/2019, 08:00 - 18:00, Exhibit Hall
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EP1.15-28 - Survival of Thymoma Is Extensive in Latin-American Patients: Results from Over 10 Years of Experience (CLICaP-LATimus) (ID 2936)
08:00 - 18:00 | Author(s): Luis Corrales
- Abstract
Background
Thymomas are a group of rare neoplasm of the anterior mediastinum. Due to their low incidence, large cooperative studies are required to evaluate outcomes. The objective of this study is to present the results and experience in treatment of this pathology in Latin-America.
Method
A retrospective multicenter cohort study was conducted by The Latin-American Consortium for the Investigation of Lung Cancer (CLICaP). Patients with histologically proven thymomas between 1997 and 2018 were included in the analysis. Variables including clinical, pathological and therapeutic outcomes were registered in a centralized manner.
Result
A total of 105 patients were included. Median age at diagnosis was 54 years old (20-84), and with 60% (n = 38) of the included patients were female. Only 11% (n=7) of the patients had an ECOG performance score >1. Twenty-four patients (22.9%, 95%CI 14.8-30.9) presented with pulmonary or distant metastatic involvement with a median of 2 metastatic sites. Furthermore, 21.9 % of patients (n=23, 95%CI 13.9-29.8%) concurrently presented myasthenia gravis. Surgery was performed in 55 patients (52.3%, 95%CI 42.8 – 61.9%), comprising of 15 tumorectomies, 37 thymectomies and 5 biopsies achieving an R0 resection rate of 78% (95%CI 67.3-89.1%). Adjuvant treatment in the form of either chemotherapy, radiotherapy or both was offered to 3(5%), 7(12.7%) and 5(9%) patients, respectively. Disease progression was documented in 10 cases (9%, 95%CI3.9-15.1%) of which 6 (60%) were locoregional, 1 (10%) distant progression and 3 (30%) both locoregional and distant. Median overall survival (OS) was estimated at around 139.5 months (95%CI 86.1-NA). Cox regression indicated that OS was significantly improved by resection (139.5 vs 25.7 months, HR 4.17 [95%CI 12.6-17.8 months]).
Conclusion
Survival in patients with thymomas continues to be very favorable, especially in patients who receive adequate local control. The benefit of adjuvant treatment in this setting remains unclear.
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EP1.15-29 - Real World Characterization and Treatment of Patients with Thymic Carcinoma: Lessons from a Latin-American Study (CLICaP-LATimus) (Now Available) (ID 2921)
08:00 - 18:00 | Author(s): Luis Corrales
- Abstract
Background
Thymic carcinoma is a rare tumor that represents a clinical challenge, especially in resource limited settings. The objective of the present study was to characterize patients who presented this disease in Latin-America.
Method
From 2014 until 2018, a multinational Latin-American cooperative retrospective cohort study was performed. Patients with histologically confirmed thymic carcinoma were included. Clinical, pathological and treatment variables were collected across 7 participating nations.
Result
A total of 31 patients were included. Median age at diagnosis was 58 years old (34-69), 48% (n=15) of individuals were women with all but 2 patients (6.5%) achieving an ECOG performance score <2. All patients debuted with Stage IV disease; 24 patients (66%, [95%CI 62-92%]) as stage IVa and 7 as stage IVb (33%, [95%CI 7-37%]) with a median LDH level of 396.5 U/L (153-1529 U/L) and a median of 2 metastatic sites. 13 (41.9%, [95%CI 25-59%]) patients received preoperatory treatment consisting of chemotherapy (n=8, 42%) and chemoradiotherapy (n=5, 16%). Among these patients only 4 (12.9%) were subjected to surgery, two of which underwent a tumorectomy and 2 a thymectomy. 28 (90%, [95%CI 79.9-100%]) received palliative chemotherapy either with sunitinib (n=7, 25%) or cytotoxic agents. Median overall survival (OS) was reached at 20.2 months (95%CI 19-NA months). Patients who received preoperative treatment had a significantly prolonged OS (17.6 vs 26 months, HR 2.93 [95%CI 1.04-8.27 months], p = 0.03).
Conclusion
Thymic carcinoma constitutes an aggressive disease that is often diagnosed in advanced stages. These results suggest that multimodal treatment can be beneficial even in locally advanced cases. Larger clinical trial validating these conclusions are warranted.
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MA07 - Clinical Questions and Potential Blood Markers for Immunotherapy (ID 125)
- Event: WCLC 2019
- Type: Mini Oral Session
- Track: Immuno-oncology
- Presentations: 1
- Now Available
- Moderators:David R Spigel, Roberto Ferrara
- Coordinates: 9/08/2019, 13:30 - 15:00, Vancouver (2003)
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MA07.08 - The Role of a Cachexia Grading System in Patients with NSCLC Treated with Immunotherapy: Implications for Response and Survival (Now Available) (ID 2046)
13:30 - 15:00 | Author(s): Luis Corrales
- Abstract
- Presentation
Background
The association between cancer-induced weight-loss (CIWL) and poor clinical outcomes is well established. However, many of these studies were performed in the chemotherapy era. Meanwhile, current standard of care for NSCLC patients has shifted towards the more efficacious immunotherapy agents (IO). IO has improved survival outcomes, nonetheless clinicians face the challenge of identifying who will derive substantial clinical benefit from these more costly agents. Response to IO is influenced by several patient-related factors, including microbiome, medications, and nutritional status.
Method
In this study we sought to evaluate the effect of cachexia in survival of NSCLC patients undergoing treatment with IO. Included patients had advanced NSCLC (IIIB, IV), who received IO agents in any line of therapy, and had a good performance status. All the patients were evaluated by the nutritionist specialist and were graded according to a previously documented cachexia scale which takes into consideration body mass index (BMI) and weight loss in order to stratify patients into 5 risk categories (0 [pre-cachexia] - 4 [refractory cachexia]). Primary endpoint was overall survival (OS), secondary endpoints included objective response rate (ORR) and progression-free survival.
Result
A total of 181 patients met the inclusion criteria and were included in the analysis. Among these 82 (45%) were classified in the first category (risk grade 0-1 [low risk]), 83 (46%) were classified in the second category (risk grade 2-3[intermediate risk]) and 9% were in the third category (risk grade 4 [high risk]). Patients classified as low-risk had a significantly longer OS compared to those with intermediate or high risk (22.4 months [95%CI: 18.7-26.1] vs. 15.7 [95%CI: 10.8-20.7] vs. 3.9 [0.0-7.8]; p<0.001; Hazard ratio: 1.81 [1.29-2.53]; p<0.001). In the multivariate analysis ORR, hemoglobin and risk category were independent factors associated with OS. Grade of cachexia was also significantly associated with ORR, with low-risk patients having a significantly higher ORR compared to intermediate and high-risk patients (36.6% vs. 17.3% vs. 25%; p=0.021). PFS was also influenced by risk category, with low risk patients having a longer PFS compared with intermediate and high-risk patients.
Conclusion
Cachexia is independently associated with worse OS in NSCLC patients who receive IO, while better nutritional status is related to higher ORR, highlighting a potential role for nutritional assessment in the selection of patients who are candidates for IO. Early assessment of nutritional status in these patients is imperative in order to timely diagnose and treat anorexia-cachexia and improve outcomes.
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P1.04 - Immuno-oncology (ID 164)
- Event: WCLC 2019
- Type: Poster Viewing in the Exhibit Hall
- Track: Immuno-oncology
- Presentations: 2
- Moderators:
- Coordinates: 9/08/2019, 09:45 - 18:00, Exhibit Hall
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P1.04-80 - Immunotherapy-Related Thrombosis: Considerations and Associated Factors in Non-Small Cell Lung Cancer (NSCLC) Patients (ID 2724)
09:45 - 18:00 | Author(s): Luis Corrales
- Abstract
Background
Widespread use of immune checkpoint inhibitors (ICIs) for the treatment of lung cancer has exposed a large number of patients to these medications, increasing the incidence of rare adverse reactions such as thromboses. The present study elaborates on factors related to the occurrence of these events.
Method
In a retrospective cohort study, a total of 48 patients, 24 who experienced thrombosis and 24 matched controls who underwent evaluation after initiation of ICIs therapy for advanced/metastatic NSCLC, were included. Clinical and pathological as well as serum inflammatory and coagulation markers were evaluated.
Result
Among the 48 patients, 46% (n=26) were female, median age was 62 years old and all patients had an ECOG performance score of < 2. The median overall survival reached by the cohort was 22.47 months. Among patients who developed thrombosis there were 8 cases of deep venous thrombosis (DVT) (33%), 13 pulmonary embolisms in addition to DVT (62.5%) and 1 case of brain venous sinus thrombosis (4.2%). Apart from expected thrombosis markers such as D dimer, differences in inflammatory and immune related markers between patients who experienced thrombosis and those who did not, were observed. Abnormal values were found in the thrombosis group for B2glycoprotein 1 (33% vs 0%, OR= 4.08, [95%CI 1.65 - 12.1], p= 0.005), B2glycoprotein 1 IgG (29.2% vs 0%, OR= 4.64, [95%CI 1.73 – 16.9], p= 0.007), C Reactive protein (83.3% vs 12.5%, OR= 35, [95%CI 7.9 - 213], p< 0.001), B2microglobulin (62.5% vs 8.3%, OR= 14, [95%CI 3.11-103.7], p = 0.002), Prothrombin time (41.7% vs 4.2%, OR= 2.4, [95%CI 1.64 -3.69], p =0.01) and C Coagulation protein (50% vs 16.6%, OR =1.79, [95%CI 1.53 – 2.91], p <0.001).
Conclusion
Abnormalities in antiphospholipid antibodies, C reactive protein, B2microglobulin and coagulation in patients who suffered thrombosis during ICI treatment suggest that this phenomenon could be the result of immune and auto-inflammatory induced intravascular dysfunction.
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P1.04-81 - Characterization of Hispanic Patients Who Experienced Hyperprogression During Treatment for Advanced NSCLC with Immunotherapy (ID 2922)
09:45 - 18:00 | Author(s): Luis Corrales
- Abstract
Background
Immunotherapy related hyperprogression is poorly characterized in Latin American patients. In this study we sought to characterize and identify factors associated with the presentation of hyperporgression after initiation of immunotherapy in patients with advanced non-small cell lung cancer (NSCLC).
Method
A multicenter international retrospective study on 110 patients was conducted. Clinical variables as well as routine blood studies were recorded before initiation of treatment. Regression analysis was used to find associations. A random forest tree analysis (RFTA) based on continuous and discrete variables was used to subcategorize patients based on occurrence of hyperprogression.
Result
Median age was 64 years (Range 34-90) and 59.8 % were male patients. ECOG performance status was >1 on 8.8% of patients. Median overall survival was 12.7 months (95% CI 9.67-14 months) and progression-free survival of 4.27 months (95% CI 3.97-5.0). 44 hyperprogressors were documented (19.8%, [95%CI 14.5-25.1%]). Median time to progression was approximately 5 weeks after initiation of treatment. Factors associated included albumin and hemoglobin levels (p = 0.046 and 0.037 respectively), presence of CNS (p= 0.0009) and bone metastasis (p = 0.004) and weight loss (p= 0.004). RFTA revealed that a leucocyte count over 5.300 cells/dl was present in all hyperprogressors.
Conclusion
Hyperprogression is a phenomenon after initiation of immunotherapy which is associated with clinical and paraclinical variables. These associations could be used to withhold certain agents and prevent its occurrence in NSCLC treatment.
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P1.14 - Targeted Therapy (ID 182)
- Event: WCLC 2019
- Type: Poster Viewing in the Exhibit Hall
- Track: Targeted Therapy
- Presentations: 1
- Moderators:
- Coordinates: 9/08/2019, 09:45 - 18:00, Exhibit Hall
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P1.14-61 - EGFR Inhibitors Plus Bevacizumab Are Superior Compared to EGFR Inhibitor Monotherapy in Advanced EGFR+ NSCLC Patients with BIM Deletions (ID 2697)
09:45 - 18:00 | Author(s): Luis Corrales
- Abstract
Background
BIM activation is essential for EGFR-TKIs triggered apoptosis in EGFR-mutant Non-small-cell lung cancer (NSCLC). A 2903-bp germline deletion in intron 2 of the BIM gene results in generation of alternatively spliced isoforms that lack the crucial BH3 domain, impairing the apoptotic response to TKIs and conferring NSCLC cells intrinsic resistance to these medications. Patients with both alterations have poor clinical evolution. The current study aimed to investigate the clinical efficacy and tolerability of EGFR-TKIs plus bevacizumab (Bev) versus EGFR-TKIs alone as first-line treatment in advanced NSCLC patients with EGFR mutations and BIM deletions (BIMdel).
Method
A retrospective analysis was conducted. BIMdel was detected using polymerase chain reaction (PCR) analysis and direct sequencing of DNA from tumor and peripheral blood cells (PBCs). We also assessed BIM protein expression by immunohistochemistry and BIM mRNA levels by RT-PCR. Clinical characteristics, overall survival (OS), progression-free-survival (PFS), objective response rate (ORR) and treatment-related adverse events were compared in the EGFR-TKIs versus EGFR-TKIs plus Bev groups.
Result
32 patients were included; 16 of them received EGFR-TKIs and 18 received EGFR-TKIs plus Bev. The addition of Bev resulted in a significantly higher ORR compared with TKIs alone (94% vs. 44%, p=0.0014). Median PFS was longer with the use of the combination compared with TKIs alone (11.1 vs. 7.77 months; p < 0.001). Median OS tended to be longer in the EGFR-TKIs plus Bev group than in TKIs alone (30.9 vs. 25.4 months; p = 0.06). EGFR-TKIs plus Bev was associated with more grade >3 hematological and thrombotic adverse events. The expression of BIM by immunohistochemistry did not influence PFS and OS, however when stratifying BIM mRNA levels by the median (≥2.2 vs. <2.1) allowed to find a prognostic trend in favor of those with higher BIM mRNA levels (32.2 vs. 25.2 months respectively; p = 0.058).
Conclusion
EGFR-TKIs plus Bev conferred a significantly higher ORR and PFS in advanced NSCLC patients with EGFR mutation and BIMdel. Further prospective studies are needed to validate these findings.
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P2.01 - Advanced NSCLC (ID 159)
- Event: WCLC 2019
- Type: Poster Viewing in the Exhibit Hall
- Track: Advanced NSCLC
- Presentations: 2
- Now Available
- Moderators:
- Coordinates: 9/09/2019, 10:15 - 18:15, Exhibit Hall
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P2.01-40 - Normalization of Carcinoembryonic Antigen Levels Is Associated with Survival Improvement in Patients with Advanced Non-Small Cell Lung Cancer (Now Available) (ID 2611)
10:15 - 18:15 | Author(s): Luis Corrales
- Abstract
Background
Serum carcinoembryonic antigen (CEA) levels are elevated in approximately 65% of the Non-small cell lung cancer (NSCLC) patients with adenocarcinoma histology. Elevated CEA levels are an independent prognostic factor for overall survival (OS) in early and advanced NSCLC stages. Previous reports from our group suggest that the decrease or increase in CEA serum levels is strongly associated with response and progression to systemic treatment. However, determination of CEA levels is not included in standard guidelines, such as National Comprehensive Cancer Network (NCNN). The aim of this study is to analyze the progression-free survival (PFS) and overall survival (OS) in NSCLC patients with elevated CEA levels at diagnosis and its association with systemic treatment response.
Method
We performed a retrospective analysis of patients with advanced NSCLC with an elevated serum level baseline of CEA (>20 ng/ml) that received treatment according to international guidelines. The serum CEA levels were measured every two cycles of platinum-based chemotherapy or a tyrosine kinase inhibitor (TKI) treatment. The change in serum CEA levels in response to treatment and the association with overall survival and progression free survival was evaluated.
Result
Between March 2004 and February 2018, 748 patients with diagnosis of advanced NSCLC and CEA levels >20 ng/mL were included in the analysis. Median age was 60.2 years old, 631 patients (84.4%) had adenocarcinoma histology. From 338 patients evaluated for EGFR mutations, 139 (31.3%) harbored an EGFR mutation. The median OS was 23.3 months (95% CI 19.4-26.9) in patients who completely normalized CEA vs 10.0 months (95% CI 8.9-11.2) in patients who did not achieved CEA normalization, with a HR 0.48 95% CI (0.35 -0.67) p <0.0001. The median OS was 15.5 months (95% CI 13.4-17.6) in patients who showed a decrease in CEA levels vs 8.8 months (95% CI 7.5-10.1) in those who did not. Reduction in CEA levels was associated with better OS, either in patients treated with TKI or platinum-based chemotherapy.
Conclusion
The normalization or decrease of the serum CEA levels is a biological marker that serves as tool associated with OS. Based on these findings and previous reports, CEA determination should be included in the clinical guidelines for NSCLC as response biomarker. Serum CEA levels should be part of the standard follow-up of NSCLC patients.
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P2.01-69 - NSCLC Mutation Frequency in the Central American and Caribbean Region (ID 2957)
10:15 - 18:15 | Presenting Author(s): Luis Corrales
- Abstract
Background
Lung Cancer (LC) constitutes a leading cause of death in the World. Non-small cell lung cancer subtype adenocarcinoma (NSCLC-A) has been associated with epidermal growth factor receptor (EGFR) mutations, which is essential for treatment decisions. The EGFR mutation frequency has been proven to have regional variability in this NSCLC-A population . The current study presents the EGFR mutation incidence and T790M frequency in NSCLC-A cases diagnosed in Central American and Caribbean(CA&C) region.
Method
A cross-sectional evaluation was performed in patients diagnosed with NSCLC-A between 2016 and 2018 in five CA&C countries. Patients were obtained from Reference Centers in Dominican Republic, Nicaragua, Panama, Honduras and Costa Rica through the AstraZeneca testing program. EGFR mutations were evaluated through Real-Time PCR.
Result
The research included 972 cases. Mean of age at the diagnosis was 62.79(28.12-90.46) years. Overall distribution of cases by gender was female in 52.37% (509/972) and male in 47.64% (463/972). For the group of antiEGFR TKI naïve patients, tissue samples were processed in 67.83% (601/886). The group of post antiEGFR TKI, patient’s plasma samples were processed in 90.70% (78/86).
AntiEGFR TKI naïve group, EGFR mutations were present in 26.64% (236 / 886), the mean of age was 63.17 years (28.12-90.46). The frequency of Exon 19 was 53.38% (126/236) and Exon 21 was 27.54%(65/236) and 11.01% (26/236) were complex mutations. T790M mutations in this treatment naïve population was 2.14%(19/886). For the group of post antiEGFR TKI patients the frequency of T790M mutation was 50.00% (43/86) where 78.57% were obtain from plasma samples.
Conclusion
The frequency of NSCLC EGFR mutation positive patients in the CA&C region was similar to that previously described in other Latin American (LA) countries. In the treatment naïve population, tissue samples remain the most important sample to analyze for EGFR mutations. T790M mutations can be seen in treatment naïve population. For patients that progressed to an antiEGFR TKI, T790M mutations were seen in a similar frequency as describe in previous LA countries. For post antiEGFR TKI patients, plasma samples were the preferred method to evaluate T790M mutations with an adequate sensibility.
