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S. Clarke
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OA 10 - Liquid Biopsy for Genomic Alterations (ID 678)
- Event: WCLC 2017
- Type: Oral
- Track: Advanced NSCLC
- Presentations: 1
- Moderators:Adrian G. Sacher, Pasi A Jänne
- Coordinates: 10/18/2017, 11:00 - 12:30, F201 + F202 (Annex Hall)
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OA 10.03 - Liquid Biopsy in the Lung Cancer Clinic: A Prospective Study of Plasma DNA next Generation Sequencing to Guide Matched Therapy (ID 8218)
11:20 - 11:30 | Author(s): S. Clarke
- Abstract
- Presentation
Background:
Liquid biopsy for plasma circulating tumor DNA (ctDNA) next generation sequencing (NGS) is now commercially available and increasingly adopted in clinical practice with a paucity of evidence based guidance. We set out to prospectively determine the utility of plasma ctDNA NGS in the lung cancer clinic.
Method:
Patients (pts) with advanced NSCLC who were driver unknown or resistance mechanism unknown were eligible. Pts were enrolled prospectively at Memorial Sloan Kettering (NY, USA) and Northern Cancer Institute (Sydney, Australia). Peripheral blood was collected in Streck tubes (10-20mL) and sent to Resolution Bioscience (Bellevue, WA) for targeted NGS of extracted DNA using a bias corrected hybrid capture 21 gene assay in a CLIA laboratory with unique reads at 3000x and sensitive detection at variant allele frequency above 0.1%. Clinical endpoints included detection of oncogenic drivers, turnaround time, comparison to tissue NGS when available, and ability to match pts to targeted therapy along with their treatment outcomes.
Result:
Seventy-six pts were prospectively accrued. Plasma NGS detected an oncogenic driver in 36% (27/76) of pts, of whom 14% (11/76) were matched to targeted therapy; including pts matched to clinical trials for HER2 exon 20 insYVMA, BRAF L597Q and MET exon14. Of the 10 evaluable pts, 10 partial responses were observed. Mean turnaround time for plasma was 6 days (3-12) vs 21 days (16-30) for tissue (P <0.0001). Plasma ctDNA was detected in 60% (46/76) of pts; detection rate was 46% (16/35) if blood was drawn on active therapy and 73% (30/41) if drawn off therapy, either at diagnosis or progression (Odds ratio 0.31, 95% CI 0.12 – 0.81; P=0.02). Of the 25 concurrent tissue NGS performed to date, there was a 96% plasma concordance with tissue and a 60% tissue concordance with plasma for driver mutations.
Conclusion:
In pts who were driver or resistance mechanism unknown, plasma NGS identified a variety of oncogenic drivers with significantly shorter turnaround time compared to tissue NGS, and matched patients onto targeted therapy with clinical benefit. Plasma ctDNA is best detected at diagnosis of metastatic disease or at progression. 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 evidence to support the incorporation of plasma NGS into practice guidelines.
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P1.01 - Advanced NSCLC (ID 757)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Advanced NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 10/16/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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P1.01-011 - Pattern of Care and Survival of ALK Rearranged Non-Small Cell Lung Cancer in Two Australian Referral Centres (ID 8893)
09:30 - 09:30 | Author(s): S. Clarke
- Abstract
Background:
ALK rearranged non-small cell lung cancer (ALK+NSCLC) represents a unique sub-group of lung cancer. Multiple effective treatments have been investigated and reported with the optimal strategy to treat advanced disease evolving rapidly with new data. First, second and now third generation single agent ALK inhibitors (ALKi) achieve excellent objective response rates (ORR), superior to chemotherapy; however, drug resistance is inevitable and remains under ongoing evaluation. Further studies are underway incorporating combination treatments, particularly immunotherapy with ALKi. Overall survival data from clinical trials continues to mature, as few non-trial series have been reported. We report our overall survival (OS) experience in treating ALK+NSCLC in a real-world cohort.
Method:
All patients with advanced lung cancer and a diagnosis of ALK+ NSCLC treated until Jan 2017 in two tertiary referral centres in Sydney, Australia were pooled together for analysis. Baseline demographic, symptom, treatment and sequencing, ORR and central nervous system (CNS) ORR, survival, toxicity and cause of death data were collected. Data will be presented on updated survival via Kaplan-Meir plots with 95% confidence intervals and a swimmer plot of treatment sequencing and ORR via RECIST 1.1.
Result:
Between 18/2/2010 and 28/1/2017, 56 ALK-rearranged lung cancer patients were identified. Median age was 63 years, 41% were female; 62% never-smokers, 63% non-Asian and 66% managed on a clinical trial. At first data cut (March 31, 2017), 52% had died. Median OS in the whole cohort was 44.6 months (95%CI: 27.8-61.4mo). Two patients were not fit for active treatment; one did not receive CNS imaging. All current ALKi therapies, chemotherapy, brain directed therapy, treatment to oligo-progressive disease and combination ALKi/immunotherapy were represented. Sixty-one percent of patients received an ALKi first line with an ORR 87%; 85% of the 34 (61%) patients who received second line therapy received an ALKi, ORR 52%. Thirty-percent received at least two lines of ALKi; 44% who received only one line of ALKi remained on and are still responding at data cut-off. Median OS in the 59% of patients with CNS metastases was 44.6mo (95% CI 14.7-74.6 mo).
Conclusion:
Analysis of real world data from two ALK referral centres in Australia reveals an imposing survival, despite many patients being managed before next generation inhibitors were available in the early line setting. While CNS disease is common in ALK patients, with aggressive local therapy and evolving treatments, survival in this cohort was comparable to those without brain metastases.
