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MA12 - Miscellaneous Biology/Pathology (ID 476)
- Event: WCLC 2016
- Type: Mini Oral Session
- Track: Biology/Pathology
- Presentations: 1
MA12.01 - Next Generation Sequencing Based Clinical Framework for Analyses of Treatment Predictive Mutations and Gene Fusions in Lung Cancer (ID 4108)
14:20 - 15:50 | Author(s): M. Planck
The use of new, emerging techniques in the search of tailored patient therapies is rapidly becoming a reality. Here we describe the optimization and implementation of next generation sequencing for treatment predictive mutation screening in parallel with gene fusion status of ALK, RET and ROS1 in non-small cell lung cancer (NSCLC) patients.
The Illumina TruSight tumor 26-gene NGS panel was validated in 81 clinical routine FFPE or cytology specimens and implemented in 533 diagnostic NSCLCs during one year of clinical analysis. In parallel, a RNA-based NanoString method was evaluated in 169 cases for gene fusion status of ALK, RET and ROS1.
We have successfully established a streamlined workflow with a 5-day turnaround time from specimen arrival to mutation report. The concordance in the validation cohort was 99% for comparable variants. In the 533 diagnostic samples, 1-2 variants were detected in 79% of the cases. Most frequently mutated genes included TP53, KRAS, EGFR, STK11, and BRAF, all with differences in mutational patterns between histological subgroups. The RNA-based NanoString assay was successfully established and validated. The success rate in the 169 cases was 80% and 10 gene fusions were found (five ALK fusions, three RET fusions and two ROS1 fusions) all in adenocarcinomas. Integration of mutation and gene fusion status revealed that 68% of adenocarcinomas, 13% of SqCCs and 56% of NSCLC-NOS harbored ≥1 actionable alteration ALK, RET, ROS1, EGFR, KRAS, PIK3CA, BRAF, NRAS, MAP2K1, ERBB2 or AKT1. Specifically, in 13.2% of the adenocarcinomas where no EGFR or ALK alteration was detected emerging targeted therapy may be considered in addition to the 15.3% of patients that was eligible for EGFR or ALK inhibitors. The corresponding proportions for SqCCs were 5.5% in addition to the 2.2%, and for NSCLC-NOS 2.5% in addition to the 11.2% eligible for EGFR or ALK inhibitors.
Next generation sequencing in combination with the NanoString technology is time- and cost efficient in the diagnostic routine for treatment predictive mutation screening and gene fusion status detection. The techniques represent valuable tools for pinpointing patients eligible to standard targeted therapies in addition to new emerging therapies.
P1.06 - Poster Session with Presenters Present (ID 458)
- Event: WCLC 2016
- Type: Poster Presenters Present
- Track: Advanced NSCLC
- Presentations: 1
- Coordinates: 12/05/2016, 14:30 - 15:45, Hall B (Poster Area)
P1.06-041 - Overall Survival and Intermediate Outcomes among Scandinavian Non-Small Cell Lung Cancer Patients: The SCAN-LEAF Study (ID 5141)
14:30 - 15:45 | Author(s): M. Planck
The past decade has seen several advances in the field of non-small cell lung cancer (NSCLC), with improved tools for tumor characterization as well as novel targeted and immune therapies. It is important to understand the current treatment landscape including treatment outcomes, in order to maximize patient benefits from these advances. SCAN-LEAF is a Scandinavian retrospective cohort study with prospective annual data cuts, providing a unique opportunity for insights into real-world clinical NSCLC practice over more than a decade. It includes clinical practice patterns of tissue biopsy, pathological diagnosis and tumor biomarker status testing, and their relationship to treatment choices and outcomes. Here, we present intermediate and survival outcomes by disease stage and histology subtype, and factors associated with survival.
SCAN-LEAF consists of a registry-based cohort including all diagnosed NSCLC patients in Denmark, Norway and Sweden (Cohort 1), and a Swedish sub-cohort (Cohort 2) supplemented with data from electronic medical records (EMRs). Based on the first data collection including data from NSCLC patients diagnosed 2005-2013, overall survival (OS; Cohort 1 & 2) and progression-free survival (PFS; Cohort 2) will be estimated using Kaplan-Meier analysis and reported as cumulative incidences (with 95% CI) by disease stage at diagnosis, histological subtype, biomarker status, presence of metastases, age and gender. Response rates (Cohort 2) will be described by treatment line in addition to stage and histology subtype. Association of stage with survival (Cohort 1 & 2) and treatment response (Cohort 2) will be analyzed by Cox regression with time to event (death or response) as outcome variable and disease stage category at diagnosis, follow-up time, and therapy line as stratification variables. In addition, the relationship between OS and intermediate outcomes, as well as predictors of OS (e.g. smoking and biomarker status, lesion location, metastasis at diagnosis), will be explored by Cox regression (Cohort 2).
Intermediate and survival outcomes for Scandinavian NSCLC patients diagnosed between 2005 and 2013, as well as any association between overall survival and factors such as patient characteristics and treatment patterns, will be presented.
The SCAN-LEAF study, expected to include >115,000 Scandinavian NSCLC patients and >2,000 sub-cohort patients diagnosed between 2005 and 2018 during the full duration of the study, will give valuable insights into current care, changing treatment patterns and patient outcomes in a real-world setting. A better understanding of factors associated with survival and intermediate outcomes among NSCLC patients will inform clinical decision-making.