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S. Geva
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P2.03b - Poster Session with Presenters Present (ID 465)
- Event: WCLC 2016
- Type: Poster Presenters Present
- Track: Advanced NSCLC
- Presentations: 2
- Moderators:
- Coordinates: 12/06/2016, 14:30 - 15:45, Hall B (Poster Area)
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P2.03b-033 - Clinical Effectiveness of Hybrid Capture-Based Massive Parallel Sequencing in Therapeutic Strategy Planning in Lung Cancer (ID 5735)
14:30 - 14:30 | Author(s): S. Geva
- Abstract
Background:
Personalized medicine significantly increases survival of lung adenocarcinoma patients. Currently, existing diagnostic guidelines include only EGFR and ALK testing, although other oncogenic drivers can be detected and targeted as well. Massive parallel sequencing (MPS) detects a wider spectrum of actionable genomic alterations (GAs) compared to regular molecular diagnostic procedures. Studies on the influence of hybrid capture-based (HC-based) MPS on therapeutic strategy are limited. In this study, we explored its impact on therapy management and clinical outcomes.
Methods:
A retrospective cohort of patients who were diagnosed with advanced stage lung cancer, and performed HC-based MPS between 11/2011 and 10/2015. Two platforms of HC-based MPS were included: a tissue based assay, and a blood based assay of circulating free DNA (cfDNA, "liquid biopsy") for tissue-exhausted cases. Demographic and clinico-pathologic characteristics, treatments, and outcome data were collected and analyzed.
Results:
One hundred and one patients were analyzed in this study: median age, 63 years; 53% females; 45% never smokers; 85% with adenocarcinoma, 19/101 performed a blood-based assay of cfDNA. HC-based MPS was carried-out upfront and after EGFR/ALK testing yielding negative or uncertain results in 15% and 85% of cases, respectively. HC-based MPS was performed before 1[st]-line therapy in 51.5% cases, and in 48.5%, after treatment failure. HC-based MPS recognized clinically actionable, National Comprehensive Cancer Network (NCCN) recommended drivers in 50% of cases, most commonly in EGFR (18%), RET (9%), ALK (8%), MET (6%) and ERBB2 (5%). EGFR/ALK aberrations were identified in 16 patients by HC-based MPS after negative prior regular testing. Therapeutic strategy was changed for 43 patients (42.6%). A higher fraction of tissue-based assays changed therapeutic strategies (n=37/82, 45%) compared to blood-based cfDNA assays (n=6/19, 32%), although not significantly. The overall response rate after treatment change to targeted therapy was 65% (complete response, 14.7%; partial response, 50%), and 62% if excluding not-previously tested patients. Median duration of targeted treatment was 26 weeks (range: 1-227). Median survival was not reached. Immunotherapy was administered in 33 patients, mostly without a detected actionable driver, presenting disease control rate of 32% and an association to tumor mutational burden.
Conclusion:
HC-based MPS changed therapeutic strategy in close to half of the patients with lung cancer, and was associated with high overall response rate, which may translate into a survival benefit.
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P2.03b-047 - The Clinical Impact of Multiplex ctDNA Gene Analysis in Lung Cancer (ID 5758)
14:30 - 14:30 | Author(s): S. Geva
- Abstract
Background:
Next-generation sequencing (NGS) of cell-free circulating tumor DNA (ctDNA) enables a non-invasive option for comprehensive genomic analysis of lung cancer patients. Currently there is insufficient data in regard to the impact of ctDNA analysis on clinical decision making. In this study, we evaluated the clinical utility of ctDNA sequencing on treatment strategy and progression-free survival.
Methods:
In this retrospective study, data was collected from files of 90 NSCLC patients monitored between the years 2011-2016 at the Thoracic Center Unit at Davidoff Cancer Center, Rabin Medical Center, Israel. The patients performed liquid biopsy NGS analysis by a commercial test (Guardant 360), in which ctDNA was extracted from plasma and analyzed by massively parallel paired end synthesis by digital NGS. This test allows the detection of somatic alterations such as point mutations, indels, fusions and copy number amplifications.
Results:
Age at diagnosis ranged between 31 and 89 years, with median age of 63 years. Sex ratio was 1:2.2. Out of 90 patients, 38 consecutive patient files have already been reviewed for clinical impact. 82% (31/38) were diagnosed with Adenocarcinoma. 5% (2/38) performed ctDNA at initial diagnosis, 48% (17/38) performed ctDNA after 1[st] line therapy due to progressive disease and the remaining 50% performed the test after multiple lines of treatment. Liquid biopsy NGS analysis allowed the detection of actionable mutations, according to NCCN guidelines, in 68% (26/38). Treatment decision was changed subsequent to NGS analysis in 34% (13/38) which received tailored targeted therapy. Interestingly, 13% (5/38) were detected with EGFR activating mutation following wild type result by standard local molecular testing based on RT-PCR from tissue biopsy. Based on the RECIST criteria of response evaluation, 30% of the patients had partial response after switching to targeted therapy, 15% had stable disease, 15% experienced progressive disease and ~40% were not evaluated yet. Survival rates will be calculated further in the study based on data availability.
Conclusion:
Our interim results analysis showed that liquid biopsy ctDNA testing revealed possible treatment options for more than two-thirds of patients analyzed, including FDA-approved drugs as well as eligibility for clinical trials. Most of the patients that were evaluated showed a positive response to treatment. Although this topic needs to be further assessed in large randomized controlled trials, these positive results emphasize the utility of liquid biopsy analysis to guide clinicians to select the right therapy for the right patient.
