C. Martin

Updated Frequency of EGFR and KRAS Mutations in NonSmall-Cell Lung Cancer in Latin America: The Latin-American Consortium for the Investigation of Lung Cancer (CLICaP)

Introduction: Previously, we reported the frequency of epidermal growth factor receptor (EGFR) and KRAS mutations in nonsmall-cell lung cancer (NSCLC) patients in Latin America. The EGFR mutation frequency was found between Asian (40%) and Caucasian (15%) populations. Here, we report the updated distribution of NSCLC mutations. Methods: A total of 5738 samples from NSCLC patients from Argentina (1713), Mexico (1417), Colombia (1939), Peru (393), Panama (174), and Costa Rica (102) were genotyped for EGFR and KRAS. Results: The median patient age was 62.2 ± 12.3 years; 53.5% were women, 46.7% had a history of smoking, and 95.2% had adenocarcinoma histology. The frequency of EGFR mutations was 26.0% (95% confidence interval [CI], 24.9–27.1; Argentina, 14.4% [12.8–15.6]; México, 34.3% [31.9–36.7]; Colombia, 24.7% [22.8–26.6]; Peru, 51.1% [46.2–55.9]; Panamá, 27.3 [20.7–33.9]; and Costa Rica, 31.4% [22.4–40.4]). The frequency of KRAS mutations was 14.0% (9.1–18.9). In patients with adenocarcinoma, EGFR mutations were independently associated with gender (30.7% females vs. 18.4% males; p < 0.001), nonsmoker status (27.4% vs. 17.1%, p < 0.001), ethnicity (mestizo/indigenous, 35.3% vs. Caucasian, 13.7%, p < 0.001), and the absence of KRAS mutation (38.1% vs. 4.7%; p < 0.001). The overall response rate to EGFR tyrosine kinase inhibitors was 60.6% (95% CI, 52–69), with a median progression-free survival and overall survival of 15.9 (95% CI, 12.420.6) and 32 months (95% CI, 26.5–37.6), respectively. Conclusion: Our findings support the genetic heterogeneity of NSCLC in Latin America, confirming that the frequency of EGFR mutations is intermediate between that observed in the Asian and Caucasian populations.

Influence of Apoptosis and Cell Cycle Regulator Proteins on Chemotherapy Response and Survival in Stage IIIA/IIIB NSCLC Patients

Background: Prognosis for non-small cell lung cancer (NSCLC) patients is very poor. Prediction of the response to treatment in individual patients may be possible using molecular biological alterations such as clinical biomarkers. We investigated the predictive value of apoptosis and cell cycle regulator proteins for neoadjuvant chemotherapy response in stage IIIA/IIIB NSCLC patients. Methods: We evaluated p53, bcl-2, p21WAF1/CIP1, p27Kip1, and Ki67 immunohistochemical expression and apoptotic index in mediastinal lymph node metastases from 23 IIIA and 10 IIIB NSCLC patients before treatment with neoadjuvant platinum-based chemotherapy. Univariate analysis was performed to evaluate the relationship between protein expression and survival or time to progression (TTP). Results: Median follow-up was 25 months (range, 4–112), median TTP was 11 months (range, 0–112), and median overall survival was 22 months (range, 4–112). Of 32 assessable patients, 18 (56%) had stable disease, 12 (38%) had a PR, and two (6%) had progressive disease. Of the 22 patients assessable for pN2 following chemotherapy, 16 (77%) were positive. Univariate analysis showed that shorter TTP correlated with progressive disease (p = 0.000), positive pN2 after chemotherapy (p = 0.026), high Ki67 (p = 0.022), and high p21WAF1/CIP1 (p = 0.038). Conclusion: Our results suggest that in IIIA/IIIB NSCLC patients, a high level of p21WAF1 expression in mediastinal lymph node metastases before neoadjuvant platinum-based chemotherapy is associated with a poor outcome. Our results suggest that expression of p21WAF1, which plays a role in preventing apoptosis, may be significant when selecting chemotherapy for NSCLC patients.

O.01: Acquired Resistance to EGFR-TKIs in EGFR-Mutant Lung Adenocarcinoma Among Hispanics (RBIOP-CLICaP)

PRESIDENTIAL SYMPOSIUM FRIDAY, AUGUST 26 e 08:00 e 09:15 O.01 Acquired Resistance to EGFR-TKIs in EGFR-Mutant Lung Adenocarcinoma Among Hispanics (RBIOP-CLICaP) Andrés F. Cardona, Oscar Arrieta, Martín I. Zapata, Leonardo Rojas, Beatriz Wills, Hernán Carranza, Noemi Reguart, Carlos Vargas, Jorge Otero, Luis Corrales-Rodriguez, Claudio Martin, Pilar Archila, Mauricio Cuello, Carlos Ortiz, Rafael Rosell Clinical And Translational Oncology Group, Clínica del Country, Bogotá/COLOMBIA, Thoracic Oncology Unit, Instituto Nacional de Cancerología, Mexico DF/MEXICO, Internal Medicine Department, Fundación Santa Fe de Bogotá, BOGOTA/COLOMBIA, Oncology Department, Hospital Universitario San Ignacio, Bogotá/COLOMBIA, Internal Medicine Department, Johns Hopkins Hospital, Baltimore/ UNITED STATES OF AMERICA, Medical Oncology, Hospital Clinic, Barcelona/SPAIN, Medical Oncology, CIMCA / Hospital San Juan de Dios, San José/COSTA RICA, Thoracic Oncology Unit, Instituto Alexander Fleming, CIUDAD DE BUENOS AIRES/ARGENTINA, Foundation for Clinical and Applied Cancer Research, Bogota/COLOMBIA, Hospital De Clínicas, Universidad de la República (UdeLAR), Montevideo/URUGUAY, Cancer Biology & Precision Medicine Program, Catalan Institute of Oncology, Barcelona/SPAIN Background: Patients with epidermal growth factor receptor (EGFR)-mutant lung carcinoma eventually develop acquired resistance to EGFR tyrosine kinase inhibitors (TKI). In 50% of these cases, a secondary EGFR mutation, T790M, underlies the acquired resistance. Other alterations include amplification of MET, PI3K mutations, changes in MAPK1, Her2, AXL and even transformation to small cell lung carcinoma (SCLC). We assessed histological, clinical characteristics and survival outcomes in Hispanic patients with EGFR mutation after disease progression. Method: 34 EGFR-mutant lung cancer patients with acquired resistance to EGFR TKIs were identified as part of a prospective registry (active between January 2011 and January 2015) in which post-progression tumor specimens were collected for molecular analysis using Journal of Thoracic Oncology Vol. 11 No. 10S: S168-S170 SNaPshot tumor genotyping assay to detect mutations in EGFR, KRAS, BRAF, PI3KCA, TP53, MET and Her2, and FISH for MET, ALK and EGFR. Samples also underwent immunohistochemistry analysis for E-cadherin, synaptophysin, CD56 and PDL1. Post-progression interventions, response and survival were assessed and compared to those with and without T790M. Results: Mean age was 59.4±13.9 years; 62% were female, 65% were never-smokers and 53% had a performance status 80%; main metastatic sites were lung (16/47%), bone (20/58%), brain (18/52%) and liver (13/38%). All patients received erlotinib as firstline treatment and documented mutations were: 60% DelE19 (Del746e750) and 40% L858R. Overall response rate (ORR) with first line TKI was 61.8% and progression free survival (PFS) was 16.8 months (range, 13.7e19.9 m). After progressing to TKI, all patients were re-biopsied, of whom 16 had the T790M mutation (47.1%); 5 had PI3K mutations (14.7), 5 had EGFR amplification (14.7%), 2 had a KRAS mutation (5.9%), 3 had MET amplification (8.8%), 2 had Her2 alterations (5.8%, deletions/insertions in e20), and one had SCLC transformation (2.9%). 79.4% received treatment after progression. ORR for post-TKI treatments was 47.1% (CR 2/PR 14) and median PFS was 8.3 months (CI95% 2.2e36.6). There were no differences in PFS according to gender (p1⁄40.10) or type of acquired alteration (p1⁄40.63). Median survival was 32.9 months (CI95% 30.4e35.3), and only the use of postprogression therapy affected OS in multivariate analysis (p1⁄40.05). Conclusion: Hispanic patients with acquired resistance to EGFR TKIs continued to be sensitive to other treatments after progression. Proportion of T790M+ patients appears to be similar to previously reported results in Caucasians.

P3.01-11 Depression and Inflammation in Patients with EGFR-Mutated Non-Small Cell Lung Cancer

Background: Lung cancer is a commonly diagnosed cancer, and the leading cause of cancer death around the world. Over 80% of lung cancer patients in México are diagnosed in advanced stage. Common symptoms include cough, dyspnea, weight loss, and chest pain. Dyspnea is one of the most common symptoms in patients with lung cancer at initial presentation with a prevalence of 55e90%. The intensity of dyspnea is an important and validated factor for assessment of quality of life (QOL) in cancer patients. In addition, improvement of healthrelated QOL and symptoms, such as dyspnea, are related with the efficacy of chemotherapeutic regimens and favorable outcome in lung cancer. In this study, we investigated the association between the degree of dyspnea and clinical outcomes to identify the prognostic role of dyspnea in hispanic patients with non-small cell lung cancer (NSCLC). Method: We retrospectively reviewed lung cancer database of Centro Oncologico Estatal ISSEMYM. From 2013 to 2016 we enrolled patients with diagnosis of advanced NSCLC. Clinicopathological information on age, sex, smoking history, histologic type, stage, Eastern Cooperative Oncology Group (ECOG) performance status, clinical outcomes and evaluation of symptoms of dyspnea at diagnosis using modified Medical Research Council (mMRC) scores from each patient were recorded. Result: A total of 120 patients with diagnosis of NSCLC were identified, of these only in 65 patients (54%) the symptom of dyspnea were detected and evaluate using modified Medical Research Council (mMRC) scores at initial diagnosis. The median age was 58 years. Among those patient with dyspnea and mMRC scores available at diagnosis, 29 (45%) patients had an mMRC score 2, while 36 (55 %) had an mMRC score < 2. In multivariate analysis, poor performance status and an mMRC score 2 were found to be significant prognostic factors for patient survival. The overall median survival for all patients was 18 months. The overall survival of patients with dyspnea (mMRC grade 2 or higher) was significantly lower than that for patients without or low grade dyspnea (median survival, 17 months vs. 35 months, p<0.036). Conclusion: In conclusion, this study showed that the dyspnea mMRC mMRC grade 2 or higher in Hispanic patient with NSCLC were significantly associated with poor prognosis. Therefore, clinicians should pay more attention to evaluation and management of dyspnea.

P2.03: Treatment of Malignant Pleural Mesothelioma Beyond First-Line Among Hispanics (MeSO-CLICaP): Track: SCLC, Mesothelioma, Thymoma

Background: Thymoma and thymic carcinoma are rare malignancies, despite being amongst the most common tumors of the anterior mediastinum. The incidence in the United States (US) is 0.13 per 100.000 habitants per year. Patients with thymoma can be asymptomatic during the diagnosis in 30% to 50% of the cases. The optimal treatment is complete resection. There are two types classification for Thymoma: Masaoka-Koga’s Classification, which assess the degree of invasion, and World Health Organization (WHO) that organize the histologic subtypes. Little information regarding thymic malignancies is available in Latin America. Method: Retrospective service database review of patients with thymoma treated at Hospital São Lucas between 2006-2016. Inclusion criteria were age 18 or older with histologically confirmed thymoma. Thymomas were classified according toWHO criteria andMasaoka staging. Results: In eligible 10 patients there were 80% males and 20% females. The mean age was 62 years and 40% were over 65 years. A complete R0 resection was achieved in all cases. No in hospital mortality or morbidity was verified. Conventional open approach was used in 90% and minimally invasive (VATS) in 10%. WHO AB type was the most common with 40% patients, followed by 30% A type, 20% B1 and 10% B2. Masaoka-Koga classification: 70% Type I, 20% IIA and 10% III. The body mass index was normal in half of patients. Myasthenia Gravis was present in 30% and all achieved at least partial response. CKAE1/3 markers were positive in 60%. Conclusion: Thymoma was most frequent in middle age men. Complete resection was achieved in all cases; predominately Masaoka I stage and WHO AB and type. CKAE1/3 markers were positive in most cases. Multicenter studies in Latin America should be performed for better understanding of this rare disease.