Background The treatment of choice for advanced non–small cell lung cancer is selected according to the presence of specific alterations. Patients should undergo molecular testing for relevant modifications and the mutational status of EGFR and translocation of ALK and ROS1 are commonly tested to offer the best intervention. In addition, the tests costs should also be taken in consideration. Therefore, this work was performed in order to evaluate the cost-effectiveness of a unique exam using NGS (next generation sequencing) versus other routinely used tests which involve RT-PCR and FISH. Methods The target population was NSCLC, adenocarcinoma, and candidates to first-line therapy. Two strategies were undertaken, strategy 1 corresponded to sequential tests with EGFR RT-PCR, then FISH for ALK and ROS1. Strategy 2 differed from 1 in that ALK and ROS1 translocation testing were performed simultaneously by FISH. Strategy 3 considered single test next-generation sequencing, a platform that includes EGFR, ALK and ROS1 genes. A decision tree analysis was used to model genetic testing options. From the test results, a microsimulation model was nested to estimate survival outcomes and costs of therapeutic options. Results The use of NGS added 24% extra true cases as well as extra costs attributed to the molecular testing. The ICER comparing NGS with sequential tests was US$ 3479.11/correct case detected. The NGS improved a slight gain in life years and QALYs. Conclusion Our results indicated that, although precise, the molecular diagnosis by NGS of patients with advanced stage NSCLC adenocarcinoma histology was not cost-effective in terms of quality-adjusted life years from the perspective of the Brazilian supplementary health system.

To evaluate the molecular testing and treatment patterns in a retrospective cohort of newly diagnosed treatment-naïve patients with locally advanced or metastatic non-small-cell lung cancer (NSCLC). METHODS: This is an observational retrospective cohort study conducted across 10 cancer centers in Brazil. Treatment-naïve patients with locally advanced or metastatic NSCLC were enrolled from January to December 2014. The following data were collected from the medical records of patients from diagnosis until the last record (death, loss to follow-up, or the end of the maximum follow-up period): demographics; medical history; smoking status; disease characteristics; previous treatments; and molecular testing patterns and results. The overall survival (OS) was also estimated. Results: A total of 391 patients from 8 different Brazilian states were included, with a median age of 64.1 years (23.7-98.7), with most patients being males (60.1%). The smoking status of 74.2% of patients was a 'former' or 'current smoker'. Stage IV NSCLC at diagnosis was observed in 82.4% of patients, with 269 of them (68.8%) presenting adenocarcinoma (ADC). Among the stage IV ADC patients, 54.0% were referred for molecular testing. Among the patients with an available epidermal growth factor receptor (EGFR) mutation status, 31 (24.0%) were EGFR-positive. The first-line treatment was a platinum-based chemotherapy for 98 patients (25.1%), while nonplatinum-based regimens were used in 54 patients (13.8%). OS data were available for 370 patients, with a median OS of 10.8 months. Never smokers had a significantly higher median OS versus current or former smokers (14.6 versus 9.1 months; log-rank p=0.003). Among the patients for whom molecular testing data were available, those with EGFR-positive results had a longer median OS (34.6 versus 12.8 months; log-rank p=0.003). Conclusion: Our findings provide relevant information for prescribers and policy decision-makers by highlighting the unmet needs of patients and the importance of molecular testing in newly diagnosed locally advanced or metastatic lung adenocarcinoma. We also highlight the respective EGFR-tyrosine kinase inhibitor treatment when the result is positive and the areas in which further efforts are required to grant access to effective treatment.

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Background: Profiling of targetable oncogenic drivers has significantly improved outcomes in patients with nonesmall cell lung cancer (NSCLC). About 40% of individuals with metastatic lung adenocarcinomas may benefit from personalized treatment with kinase inhibitors. There is limited data of the distribution of oncogenic drivers other than ALK and EGFR in our region. In this study we performed next generation sequence (NGS) to study the distribution of molecular alterations in patients with advanced lung cancer. Herein we present preliminary data of a single center experience. Method: A prospective, single-center, observational study was conducted. We included 125 patients > 18 years old with NSCLC from 06/2015 to 06/2018. NGS was performed with DNA/RNA from formalin-fixed, paraffin-embedded (FFPE) tumor tissue with OncomineTM Focus Assay (Ion 520 Chip), sequenced in Ion S5 Next Generation Sequencing Systems, analyzed with Ion ReporterTM Software 5.2.1 and informed with Ion TorrentTM OncomineTM Knowledgebase Reporter. Results were compared with those from standard pathology and molecular biology techniques, when available, like immunohistochemistry (IHQ) and FISH for ROS1 and ALK and PCR and sequencing for EGFR. We report partial results from the first 51 patients included. Results: Median (IQR) age was 65 years (59-74), n¼28 were men (55%), smoker/former-smoker/non-smoker n¼11 (21.6%)/ n¼31 (60.8%)/ n¼9 (17.6%), Stage IIIa n¼7 (13.7%), IIIb n¼6 (11.8%), IV n¼38 (74.5%). Adenocarcinoma histology n¼43 (84.3%). Assay performance was 100% for DNA analysis and 60.8% for the study of fusions and CNV from RNA. Distribution of molecular alterations: KRAS n¼18 (35%), EGFR n¼8 (17.6%) BRAF n¼2 (4%), METex14 skipping n¼2 (4%), HER2 n¼1 (2%), ALK rearrangements n¼5 (10%) y ROS1 rearrangements n¼2 (4%). Co-mutations: EGFR+BRAF n¼1, ALK+KRAS n¼1, KRAS+AKT n¼1. Conclusion: NGS allows to optimize the molecular profiling of tumors from patients with lung cancer in our population. It can simultaneously identify mutations, rearrangements and alternative splicing events in key oncogenic drivers that can select patients to treatment with kinase inhibitors, currently available in the daily practice and in clinical development.

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