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Chong-Rui Xu
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P1.01 - Advanced NSCLC (ID 158)
- Event: WCLC 2019
- Type: Poster Viewing in the Exhibit Hall
- Track: Advanced NSCLC
- Presentations: 2
- Moderators:
- Coordinates: 9/08/2019, 09:45 - 18:00, Exhibit Hall
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P1.01-104 - Survivals in ROS1-Rearranged Advanced Non-Small-Cell Lung Cancer Treated with First-Line Crizotinib (ID 1735)
09:45 - 18:00 | Author(s): Chong-Rui Xu
- Abstract
Background
The c-ros oncogene 1 (ROS1)-rearranged non-small-cell lung cancer (NSCLC) can be treated effectively with crizotinib, a tyrosine kinase inhibitor (TKI) of anaplastic lymphoma kinase (ALK), ROS1, and mesenchymal-epithelial transition (MET). However, few studies have investigated on survivals in ROS1-rearranged advanced NSCLC patients treated with first-line crizotinib.
Method
We retrospectively analyzed clinicopathological and survival data of ROS1-rearranged patients with advanced NSCLC treated with crizotinib between August 2013 and January 2019 at the Guangdong Provincial People's Hospital. ROS1 rearrangements were detected by Reverse Transcription-Ploymerase Chain Reaction(RT/PCR),Fluorescence in situhybridization (FISH), or Next-generation Sequencing (NGS) . Overall survival (OS) and progression-free survival (PFS) were compared between first-line crizotinib, chemotherapy followed by crizotinib and first-line chemotherapy without any subsequent targeted therapy.
Result
Among totally 40 patients with ROS1-rearranged advanced NSCLC, 29 were treated with crizotinib (16 with first-line; 13 with second- or further-line), and 11 were not treated with crizotinib at data cutoff (April 4, 2019). Median OS was significantly prolonged in patients with first-line crizotinib (N=16) than those with first-line chemotherapy followed by subsequent crizotinib (N=9), not reached vs. 27.1 months, P=0.042. However, there was no significant difference in median PFS between the two groups, 16.3 vs. 5.7 months, P=0.054. Meanwhile, first-line crizotinib (N=16) was significantly superior to first-line chemotherapy without any subsequent targeted therapy (N=8) in both median OS (not reached vs. 9.1 months, P=0.024) and PFS (16.3 vs. 4.8 months, P=0.017).
Conclusion
First-line crizotinib prolongs survivals than chemotherapy for patients with ROS1-rearranged advanced NSCLC.
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P1.01-122 - A Clinical Utility Study of Plasma DNA Next Generation Sequencing Guided Treatment of Uncommon Drivers in Advanced Non-Small-Cell Lung Cancers (ID 2997)
09:45 - 18:00 | Author(s): Chong-Rui Xu
- Abstract
Background
Although EGFR and ALK testing in non-small-cell lung cancers (NSCLC) is now considered standard practice, next generation sequencing (NGS) for extended molecular testing of uncommon drivers is often difficult to perform in the community due to factors surrounding tissue adequacy, availability and turnaround time. We set out to prospectively determine the clinical utility of plasma ctDNA NGS in detecting uncommon actionable drivers and their plasma guided treatment response.
Method
Patients with advanced NSCLC who were driver unknown after routine EGFR and ALK testing were eligible. Patients were enrolled prospectively at Memorial Sloan Kettering Cancer Center (NY, USA) and Northern Cancer Institute (Sydney, Australia). Peripheral blood (10-20mL) was collected and sent to Resolution Bioscience (Kirkland, WA) for targeted ctDNA NGS using a bias-corrected hybrid-capture 21 gene assay in a CLIA laboratory achieving a mean unique read of at least 3000x and sensitivity above 0.1%. Clinical endpoints included detection of uncommon oncogenic drivers defined as actionable alterations in ROS1, RET, BRAF, MET, HER2, turnaround time, concordance with tissue NGS when available, and plasma guided treatment outcome.
Result
614 patients were prospectively accrued. Plasma NGS detected an uncommon oncogenic driver in 7% (45/614) of patients including ROS1, RET fusions, BRAF, MET exon 14 and HER2 exon 20 mutations, of whom 3% (20/614) were matched to targeted therapy producing 12 partial responses. Mean turnaround time for plasma NGS was significantly shorter than tissue NGS (10 vs 25 days, P <0.0001). 399 patients had concurrent tissue NGS results available for concordance analysis; Overall concordance, defined as the proportion of patients for whom an uncommon driver was uniformly detected or absent in both plasma and tissue NGS, was 94.7% (378/399, 95% confidence interval [CI] 92.1 – 96.7%). Among patients who tested plasma NGS positive for uncommon drivers, 87.5% (28/32, 95% CI 71.0-96.5%) were concordant on tissue NGS, and among patients tested tissue NGS positive for uncommon driver, 62.2% (28/45, 95% CI 46.5-76.2%) were concordant on plasma NGS.
Conclusion
Plasma NGS uncovered uncommon oncogenic drivers with faster turnaround time than tissue NGS, directly matched patients to targeted therapy and produced clinical responses independent of tissue results. A positive finding of an oncogenic driver in plasma is highly specific and can immediately guide treatment, but a negative finding may still require tissue biopsy. Our findings provide prospective evidence to support a “blood first” approach in molecular diagnostics for the care of patients with NSCLC.
