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Richard B Lanman
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MA02 - Improving Outcomes for Patients with Lung Cancer (ID 895)
- Event: WCLC 2018
- Type: Mini Oral Abstract Session
- Track: Advanced NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 9/24/2018, 10:30 - 12:00, Room 201 BD
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MA02.11 - Achieving Value in Cancer Diagnostics: Blood Versus Tissue Molecular Profiling - A Prospective Canadian Study (VALUE) (ID 13611)
11:40 - 11:45 | Author(s): Richard B Lanman
- Abstract
- Presentation
Background
Cell-free DNA (cfDNA) next-generation sequencing (NGS) has emerged as an effective molecular profiling technique that is potentially faster and cost-saving in comparison to standard-of-care (SOC) tumour biopsy and tissue-based profiling. In a public payer system, the added value of cfDNA blood-based profiling compared to SOC remains unknown. This study will determine the incremental clinical utility and cost of cfDNA NGS versus SOC genotyping in patients with advanced non-squamous non-small cell lung cancer (NSCLC).
a9ded1e5ce5d75814730bb4caaf49419 Method
This multicentre, non-randomized, longitudinal study will be conducted at 6 sites across Canada (BC, Alberta, Ontario, Quebec). The Guardant360® assay will be used to perform plasma-based cfDNA testing, and includes mutations, rearrangements and copy number variations in 73 known cancer associated genes. Two patient cohorts will be recruited: (1) treatment naïve patients with ≤10 pack year smoking history; and (2) patients with known abnormalities of EGFR, ALK, ROS-1 or BRAF after disease progression on all standard targeted therapies. SOC tissue profiling will be performed for all patients per institutional standards. The study will begin recruiting in May 2018, with estimated completion in 12 months. The primary endpoints are comparison of response rate (RR), progression-free survival (PFS) and time-to-treatment failure (TTF) using cfDNA versus tissue genomic testing. Secondary endpoints include time to treatment initiation, number of actionable genomic abnormalities identified, result turnaround time, potentially avoidable repeat tissue biopsies, costs, patient-reported quality of life (EQ-5D) and willingness-to-pay. Exploratory analyses of treatment outcomes in selected molecular subgroups will also be undertaken, including response to immunotherapy in those with KRAS/STK11 co-mutations. A decision-analytic model will be developed to perform cost-consequence analyses using a cfDNA versus tissue-based approach.
4c3880bb027f159e801041b1021e88e8 Result
A total of 210 patients will be recruited across Canada, (Cohort 1 N=150, Cohort 2 N=60). Based on testing with either blood-based GUARDANT360TM or tissue-based profiling, the costs and benefits of blood-based profiling either at initial diagnosis or upon TKI progression will be determined versus initial or repeat tumour biopsy and tissue-based profiling. Data from patients accrued until 08/2018 will be presented at the meeting.
8eea62084ca7e541d918e823422bd82e Conclusion
This study will determine the added value of cfDNA blood-based genotyping compared to SOC from the perspective of a public payer system (Canada).
6f8b794f3246b0c1e1780bb4d4d5dc53Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.
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MA16 - Novel Mechanisms for Molecular Profiling (ID 917)
- Event: WCLC 2018
- Type: Mini Oral Abstract Session
- Track: Advanced NSCLC
- Presentations: 2
- Moderators:
- Coordinates: 9/25/2018, 13:30 - 15:00, Room 203 BD
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MA16.01 - Frequency and Genomic Context of Emerging Markers for Molecular Testing in Lung Adenocarcinoma in Cell-Free DNA NGS Analysis (ID 13465)
13:30 - 13:35 | Author(s): Richard B Lanman
- Abstract
- Presentation
Background
The recently updated CAP/IASLC/AMP lung cancer molecular testing guideline (Lindeman et al 2018) recommends several genes be analyzed by next-generation sequencing (NGS) in lung adenocarcinoma (LUAD), including EGFR, ALK, BRAF, KRAS, and others. It also includes a list of 20 emerging markers (EMs) for molecular testing and suggests practitioners remain aware of these and other genes between guideline updates. We investigated the frequency of genomic alterations (GAs) in several of these EMs in a cohort of patients with advanced lung adenocarcinoma who underwent clinical cell-free DNA (cfDNA) NGS analysis and assessed co-occurrence with canonical driver GAs.
a9ded1e5ce5d75814730bb4caaf49419 Method
Genomic data was reviewed from 6530 patients with at least one GA detected on clinical Guardant360 cfDNA NGS testing (Guardant Health, Inc) with an indicated diagnosis of lung adenocarcinoma from 11/25/16-3/1/18. Synonymous alterations were excluded from further analyses.
4c3880bb027f159e801041b1021e88e8 Result
2600 patients (40%) had at least one nonsynonymous alteration in the EM genes assessed; excluding GAs classified as variants of unknown significance (VUS), 1350 patients (21%) had at least one characterized alteration. Table 1 shows number and frequency of GAs observed per patient by gene and alteration type. Of EMs assessed, GAs were observed most commonly in NF1, PIK3CA, PDGFRA, KIT, and FGFR1-2. GAs in multiple EMs, including RIT1, NRAS, FGFR2-3, NTRK1, KIT, and AKT1, were observed co-occurring with established driver alterations, often in a genomic context consistent with resistance to targeted therapy at allelic fractions suggestive of subclonality.
8eea62084ca7e541d918e823422bd82e Conclusion
Effective therapies are continually emerging for a growing number of molecular biomarkers in lung cancer. Comprehensive genomic profiling with cfDNA NGS can identify GAs in both recommended and EM genes to guide therapeutic decision-making and catalyze clinical trial enrollment. Further investigation of mutual exclusivity and co-occurrence of established drivers and EMs may reveal novel resistance mechanisms and facilitate identification of rational combination therapeutic strategies.
6f8b794f3246b0c1e1780bb4d4d5dc53Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.
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MA16.08 - Clinical Utility of Detecting ROS1 Genetic Alterations in Plasma (ID 13522)
14:25 - 14:30 | Author(s): Richard B Lanman
- Abstract
- Presentation
Background
ROS1-rearranged lung cancer harbors an oncogenic fusion protein created by the juxtaposition of the ROS1 gene to various fusion partners. Due to the lack of a conserved breakpoint and inclusion of intronic segments, ROS1 rearrangements can be challenging to identify with DNA-based sequencing approaches. The feasibility and clinical utility of detecting ROS1 fusions in circulating tumor DNA is not well established.
a9ded1e5ce5d75814730bb4caaf49419 Method
The Guardant360 de-identified database was queried to identify lung cancer cases with plasma ROS1 fusions and describe the molecular features of the ROS1-rearranged cohort. In addition, we performed longitudinal analysis of plasma specimens from four patients at our institution who were treated with next-generation ROS1 inhibitors after progressing on crizotinib.
4c3880bb027f159e801041b1021e88e8 Result
From review of 24,009 plasma specimens from lung cancer patients, we identified 56 patients with ROS1 fusions. CD74 was the most common of 7 identified fusion partners [n=35 (62%) CD74, n=7 (12.5%) SDC4, n=7 (12.5%) EZR, n=3 (5%) TPM3, n=2 (4%) TFG, and n=1 (2%) each of CCDC6 and SLC34A2]. ROS1 fusions commonly co-occurred with TP53 mutations (n=36, 64%) and genes involved in cell-cycle regulation (n=11, 20%) or the WNT/ß-catenin pathway (n=16, 29%). In 4 (80%) of 5 cases where plasma genotyping occurred at crizotinib progression, we identified a putative resistance mechanism, including a ROS1 resistance mutation in 3 patients (n=2 G2032R & n=1 L2026M) and a BRAF V600E mutation in 1 patient. We analyzed longitudinal plasma specimens from 4 patients with crizotinib-resistant lung cancer who were subsequently treated with a next-generation ROS1 inhibitor (n=3 lorlatinib, n=1 entrectinib). One patient treated with lorlatinib had a pretreatment ROS1 G2032R mutation (in plasma and tissue); plasma analysis revealed stability of the G2032R allelic fraction in the setting of primary progression of pleural disease. Of the 2 patients without pretreatment ROS1 mutations who received lorlatinib, one developed a ROS1 G2032R mutation after initial response to treatment. The second patient experienced primary progression and plasma genotyping revealed low level FGFR1 copy number gain (3.3 copies); pre-crizotinib plasma was not available for comparison. One patient had a plasma PIK3CA E545K mutation at the time of crizotinib progression, and did not respond to next-line entrectinib.
8eea62084ca7e541d918e823422bd82e Conclusion
Next-generation sequencing can be used to detect ROS1 fusions and resistance mutations in plasma. Longitudinal plasma analysis may provide insight into the activity of investigational drugs against ROS1 mutations that mediate resistance to crizotinib.
6f8b794f3246b0c1e1780bb4d4d5dc53Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.
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MA26 - New Therapies and Emerging Data in ALK, EGFR and ROS1 (ID 930)
- Event: WCLC 2018
- Type: Mini Oral Abstract Session
- Track: Targeted Therapy
- Presentations: 1
- Moderators:
- Coordinates: 9/26/2018, 13:30 - 15:00, Room 201 BD
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MA26.03 - Activity of Osimertinib and the Selective RET Inhibitor BLU-667 in an EGFR-Mutant Patient with Acquired RET Rearrangement (ID 14731)
13:40 - 13:45 | Author(s): Richard B Lanman
- Abstract
- Presentation
Background
The spectrum of acquired resistance (AR) to osimertinib is not yet fully characterized. We present a single-center cohort of osimertinib AR biopsies and results of a patient with RET-mediated AR treated with the investigational RET-specific TKI BLU-667 and osimertinib.
a9ded1e5ce5d75814730bb4caaf49419 Method
We assayed tissue via SNaPshot or Foundation One next-generation sequencing (NGS) and plasma via Guardant360 NGS under an IRB-approved protocol. In vitro studies assessed implications of RET fusions in EGFR-mutant cancers. We treated one patient with osimertinib/BLU-667 using an IRB and FDA-approved compassionate use protocol.
4c3880bb027f159e801041b1021e88e8 Result
41 EGFR-mutant patients with AR to osimertinib were assessed histologically and queried by tissue NGS (n=22), plasma NGS (n=9) or both (n=10). Key AR findings: SCLC transformation (2/32 tissue); EGFR C797S (5/32 tissue, 5/19 plasma, all cis with T790M); MET amplification (7/32 tissue, 3/19 plasma); BRAF rearrangement (2/32 tissue) and CCDC6-RET rearrangement (1/32 tissue, 1/19 plasma [distinct case]).
CCDC6-RET was expressed in PC9 (EGFR del19) and MGH134 (EGFR L858R/T790M) cells, which maintained MAPK signaling and conferred resistance to osimertinib and afatinib. Inhibition of RET by BLU-667 or cabozantinib resensitized cells expressing CCDC6-RET to EGFR inhibition.
A 60-year-old woman with EGFR del19 progressed on afatinib (T790M+), then osimertinib. Tissue biopsy at osimertinib AR showed acquired CCDC6-RET (T790-wt). She began osimertinib 80mg/BLU-667 200mg daily x2 weeks, then BLU-667 was increased to 300mg daily. Her dyspnea improved within days of initiation. Scans after 8 weeks revealed a marked response with RECIST tumor shrinkage of 78% (Figure). She experienced only grade 1 toxicities of fatigue, leukopenia, hypertension, dry mouth, and elevated transaminases.
8eea62084ca7e541d918e823422bd82e Conclusion
RET rearrangements are rare but recurrent in EGFR-mutant patients with AR to osimertinib. In vivo models suggest they mediate AR and this patient provides proof-of-concept that combination EGFR+RET inhibition with osimertinib/BLU-667 is a well-tolerated and effective regimen for RET-mediated AR. Further study is ongoing.
6f8b794f3246b0c1e1780bb4d4d5dc53Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.
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P1.09 - Pathology (Not CME Accredited Session) (ID 941)
- Event: WCLC 2018
- Type: Poster Viewing in the Exhibit Hall
- Track:
- Presentations: 1
- Moderators:
- Coordinates: 9/24/2018, 16:45 - 18:00, Exhibit Hall
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P1.09-21 - Circulating Tumor DNA Improves Genotypification and Detection of Targetable Alterations in Selected Lung Cancer Patients (ID 12218)
16:45 - 18:00 | Author(s): Richard B Lanman
- Abstract
Background
Several studies have shown that NSCLC genomic background among Hispanics differs from other populations. The finding of low frequency genomic alterations in cfDNA to increase diagnostic accuracy in NSCLC could refine the treatment. We hypothesized that cfDNA can be an alternative or complement for detection of low frequency genomic targets. We aimed to understand the landscape of cfDNA-identified genomic drivers in a cohort of patients (pts) with NSCLC of Hispanic ancestry.
a9ded1e5ce5d75814730bb4caaf49419 Method
We collected data from 51 Hispanic pts (Mexico and Colombia) with advanced NSCLC (Stage III/IV) who previously underwent tissue screening for ALK, EGFR, and ROS1. CfDNA was extracted from plasma and analyzed by a commercial NGS test (Guardant360â) which detects genomic alterations (alts) in up to 73 genes.
4c3880bb027f159e801041b1021e88e8 Result
Median age was 56 years (31-83). Most pts were female (64.7%) and never smokers (76.5%). 94% of cases (48/51) had cfDNA detectable alts with a mean number of 3.37 cfDNA alts per test (range, 1 -10). Of the 48 pts with cfDNA genomic alts, 23 (47.9%) had a known genomic driver (EGFR (27.4%), TP53 (13.7%), ALK (7.8%), KRAS (5.8%), and BRAF (3.9%)). Interestingly, cfDNA was able to detect some genomic alts previously undetected by tissue biopsy (either due to false negatives or to technical limitations such as insufficient or low-quality DNA). In the case of EGFR, 12 pts had EGFR alts through cfDNA which were previously undetected by tissue biopsy. Similarly, cfDNA detected 3 alterations in ALK which were previously undetected by tissue sample. Of 48 pts, 35.4% were switched to a targeted therapy as a result of alts detected through cfDNA, with adequate responses: disease control rate was 82.4% (partial response 47.2% and stable disease 35.2%) and progression free survival was 7.4 months (95%CI 2.6-28.1).
8eea62084ca7e541d918e823422bd82e Conclusion
In a selected population of young Hispanics (especially never smokers and women) with NSCLC the use of comprehensive cfDNA analysis allowed a treatment change in 35% of the cases. Our data confirms the usefulness of Guardant360â as non-invasive panel to identify genomic alts in cfDNA.
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P1.13 - Targeted Therapy (Not CME Accredited Session) (ID 945)
- Event: WCLC 2018
- Type: Poster Viewing in the Exhibit Hall
- Track:
- Presentations: 1
- Moderators:
- Coordinates: 9/24/2018, 16:45 - 18:00, Exhibit Hall
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P1.13-37 - Clinical Evaluation of Plasma-Based (cfDNA) Genomic Profiling in Over 1,000 Patients with Advanced Non-Small Cell Lung Cancer (ID 14332)
16:45 - 18:00 | Author(s): Richard B Lanman
- Abstract
Background
Tumor genomic information from a simple blood collection revealing actionable mutation can improve clinical outcome without the need for an invasive tissue biopsy. We report on the clinical utility of a cell-free DNA (cfDNA) next generation sequencing (NGS) blood test in our patients with non-small cell lung cancers (NSCLC) and the outcome of treatments with targeted therapies based on the reported mutations.
a9ded1e5ce5d75814730bb4caaf49419 Method
From May 2015 to February 2017, 1078 blood samples from 1011 consecutive patients with a diagnosis of NSCLC were collected and analyzed using next-generation sequencing of cfDNA with a panel of up to 70 cancer-related genes at a CLIA-certified lab (Guardant360, Guardant Health, Redwood City, CA) with reported sensitivity of 0.02% mutant allele fraction with high specificity (> 99.9999%) (CCR 2018 (17):3831). Patients in this retrospective study received targeted therapy as indicated by cfDNA molecular profiling. Tumor response was evaluated by RECIST V1.1 and standard clinical evaluation.
4c3880bb027f159e801041b1021e88e8 Result
From 1011 patients, 1078 cfDNA tests sent (additional follow-up tests: 1 in 64 patients and 2 in 3 patients). In 223/1011 (22%) patients had cfDNA report with at least 1 targetable mutations; with 48/223 (22%) patients meeting criteria for this retrospective review. Study population were 31 female:17 male, median age of 63 years (ranged:31-94). The rationale for the blood test included: insufficient tissue or not available (32%), addition to tissue molecular analysis (17%), alternative to tissue biopsy(10%), on-going treatment evaluation/resistance (41%). Mutations included:EGFR T790M (15), EGFR exon 19del (12), EGFR L858R (9), EGFR exon 20 insertion (4), EGFR others (1), ALK gene fusions (5) and MET exon 14 skipping (2). The median line of therapy was 2(ranged:1-7) with 28 patients receiving TKI as 1st line of therapy based on cfDNA mutations. With targeted treatments based on ctDNA results, the responses (RECIST V1.1) were: CR(3), PR(26), SD(14) and PD(4); median PFS was 8.5 months (ranged:1-26mos) for the overall population with 4 patients still receiving targeted therapy. Median PFS was 9.5 months (ranged:1-20 months) for those receiving TKI as 1st line.
8eea62084ca7e541d918e823422bd82e Conclusion
This is the largest analysis of response rates with cfDNA directed therapy in advanced NSCLC and demonstrates positive clinical outcomes in patients treated with targeted therapy based on plasma identified biomarkers.
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P2.15 - Treatment in the Real World - Support, Survivorship, Systems Research (Not CME Accredited Session) (ID 964)
- Event: WCLC 2018
- Type: Poster Viewing in the Exhibit Hall
- Track:
- Presentations: 1
- Moderators:
- Coordinates: 9/25/2018, 16:45 - 18:00, Exhibit Hall
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P2.15-16 - Clinical Economic Impact of Improved Genotyping in Patients with Advanced Non-Small Cell Lung Adenocarcinoma (NSCLC) (ID 14255)
16:45 - 18:00 | Author(s): Richard B Lanman
- Abstract
Background
Comprehensive genomic profiling (CGP) at diagnosis and progression identifies NSCLC patients who may benefit from targeted therapies and are unlikely to respond to immunotherapy, however many patients are incompletely or undergenotyped. We developed a cost benefit model to evaluate the clinical and economic impact of using plasma-based cfDNA CGP to guide treatment decisions in first- and second-line advanced NSCLC.
a9ded1e5ce5d75814730bb4caaf49419 Method
The model compares the clinical and economic impact of an NCCN guideline driven care paradigm, utilizing Guardant360â (G360), a CLIA certified, CAP accredited, NYSDOH approved cfDNA CGP test, for stage IIIB/IV NSCLC patients versus the current care paradigm and assesses the impact of additional genomic information to aid in therapy selection and subsequent effects on biopsy rates, drug costs, and clinical outcomes (RR, PFS, and median OS). The model targeted patients with NSCLC receiving first or second line treatment enrolled in a U.S. Commercial Health Plan with 10 million lives. Frequency of NCCN genomic targets in first-line patients was per The Cancer Genome Atlas with second-line frequencies modified to reflect the first-line testing, genotyping QNS, biopsy, and undergenotyping rates. Therapy current care distributions were derived from 2017 Integra Connect’s proprietary database.
4c3880bb027f159e801041b1021e88e8 Result
Under the guideline directed care, immunotherapy and chemotherapy use decreased as patients are re-assigned to targeted therapy in both first line QNS and second line progression settings, resulting in improved clinical outcomes, including a second line repeat tissue biopsy rate reduction. Individual and overall cost savings were observed in both settings (Table).
8eea62084ca7e541d918e823422bd82e ConclusionFirst-Line QNS Patients
Second-Line Patients
Current
Guideline Directed
Difference
Current
Guideline Directed
Difference
Overall Patient Cohort
Immunotherapy Monotherapy
19.2%
13.2%
- 6.00%
52.5%
42.9%
- 9.6%
Immunotherapy + Chemotherapy
5.6%
3.9%
- 1.7%
3.3%
2.7%
- 0.6%
Chemotherapy +/- Biologics
75.2%
51.7%
- 23.5%
35.7%
29.2%
- 6.5%
Targeted Therapy
0%
31.3%
+ 31.3%
8.6%
25.3%
+ 16.7%
Overall Clinical Outcome Measures
Response Rate
18.1%
28.3%
+ 10.2%
20.9%
25.7%
+ 4.8%
Progression Free Survival (months)
4.7
6.0
+ 1.3
4.7
5.6
+ 0.9
Overall Survival (months)
11.1
12.6
+ 1.5
11.0
12.1
+ 1.1
Reassigned Patient Cohort
Immunotherapy Monotherapy
6.0%
-
-6.0%
9.6%
-
- 9.6%
Immunotherapy + Chemotherapy
1.8%
-
- 1.8%
0.6%%
-
- 0.6%
Chemotherapy +/- Biologics
23.5%
-
- 23.5%
6.5%
-
- 6.5%
Targeted Therapy
-
31.3%
+ 31.3%
-
16.7%
+ 16.7%
Clinical Outcome Measures for Reassigned Patients
Response Rate
18.1%
50.7%
+ 32.6%
17.7%
49.5%
+ 31.8%
Progression Free Survival (months)
4.7
8.8
+ 4.0
4.2
9.7
+ 5.5
Overall Survival (months)
11.1
15.9
+ 4.9
10.3
17.3
+ 7.0
Second-line re-biopsy rate
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-
25%
11%
-14%
Overall Cost per Patient
$140,950
$130,141
-$10,809
$175,563
$161,810
- $13,753
Overall Total Cost
$55,516,110
$51,258,713
-$4,257,397
$209,553,002
$193,136,843
- $16,416,159
cfDNA CGP application in first line tissue QNS and second line progressing advanced NSCLC patients improved outcomes and cost savings. Shifting from chemotherapy and immunotherapy to relatively more efficacious, less toxic, and less expensive targeted therapies resulted in improved patient outcomes. Cost savings are driven by decrease in immunotherapy, infusion costs, emergency room/hospital visits, and avoidance of tissue biopsy.
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P3.01 - Advanced NSCLC (Not CME Accredited Session) (ID 967)
- Event: WCLC 2018
- Type: Poster Viewing in the Exhibit Hall
- Track:
- Presentations: 1
- Moderators:
- Coordinates: 9/26/2018, 12:00 - 13:30, Exhibit Hall
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P3.01-28 - The Clinical Impact of Comprehensive cfDNA Genomic Testing in Lung Cancer (ID 13878)
12:00 - 13:30 | Author(s): Richard B Lanman
- Abstract
Background
Next-generation sequencing (NGS) of cell-free circulating tumor DNA (cfDNA) enables a non-invasive option for comprehensive genomic analysis of non-small cell lung cancer (NSCLC) patients. Although plasma-detected genomic alterations have been shown to predict targeted therapy response, evidence of durability of response is lacking or limited to small cohorts as is the impact of cfDNA NGS results on clinical decision making.
a9ded1e5ce5d75814730bb4caaf49419 Method
In this retrospective study, data was collected on stage IIIB/IV NSCLC patients between the years 2014-2017 in Israel. We utilized cfDNA NGS (Guardant360) which covers the seven genes targetable with FDA-approved therapies in NSCLC.
4c3880bb027f159e801041b1021e88e8 Result
116 consecutively NSCLC patients were tested, 41.4% (48/116) before 1st line therapy (Group A), 34.5% (40/116) upon progression on chemotherapy or immunotherapy (Group B1) and 24.1% (28/116) upon progression on EGFR TKIs (Group B2). Targetable genomic alterations were found in 65% of group A (15/48), 53% in group B1 (21/40) and 71% in group B2 (20/28). Treatment decision was changed to targeted therapy based on cfDNA NGS analysis in 23% (11/48), 25% (10/40) and 32% (9/28), respectively (total cohort 26%; 30/116). Response assessment (RECIST) showed complete response in 4% (1/28), partial response in 39% (11/28), stable disease in 32% (9/28) and progressive disease in 25% (7/28). Total objective response rate (ORR) was 43% and disease control rate was 75% for 5 months treatment duration.
8eea62084ca7e541d918e823422bd82e Conclusion
Comprehensive cfDNA testing impacted clinical decisions in 23% of naïve patients, 25% in patients who progressed on chemotherapy and 32% in EGFR TKI progressors. Median treatment duration was 5 months. This retrospective study extends previous reports by showing that responses based on cfDNA are durable and change treatment decisions at initial presentation and at progression.
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P3.04 - Immunooncology (Not CME Accredited Session) (ID 970)
- Event: WCLC 2018
- Type: Poster Viewing in the Exhibit Hall
- Track:
- Presentations: 1
- Moderators:
- Coordinates: 9/26/2018, 12:00 - 13:30, Exhibit Hall
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P3.04-11 - The Influence of Circulating Tumor DNA Analysis on Response to Immunotherapy in Non-Small Cell Lung Cancer (NSCLC) (ID 13810)
12:00 - 13:30 | Author(s): Richard B Lanman
- Abstract
Background
In advanced NSCLC, immunotherapy has demonstrated good response rates with some responses being remarkably durable, however emerging biomarkers predictive of response (or lack thereof) include PD-L1 expression, tumor mutation burden (TMB), genomic alterations in EGFR/ALK/ROS1 and KRAS/TP53/STK11 mutations, all competing for limited tissue biopsy samples. Therefore, we investigated whether these biomarkers can be detected from a non-invasive plasma sample. In particular, challenges to assessment of TMB with cell-free DNA next-generation sequencing (NGS) include the limited size of liquid biopsy gene panels and the fact that low shedding of tumor DNA into circulation may fail to detect hypermutated tumors. We previously reported, in a modest 27 advanced NSCLC cohort, that TMB can be ascertained with a 73-gene cfDNA NGS panel that adjusts for the degree of tumor shedding, and here investigate whether detection of TMB and the above genomic mutations can be used to predict immune checkpoint inhibitor response in a larger cohort.
a9ded1e5ce5d75814730bb4caaf49419 Method
In this retrospective study, data were collected on NSCLC patients treated in multiple medical centers in Israel between 2014 and 2017. We used NGS on cell-free circulating tumor DNA (ctDNA) to evaluate whether mutational burden and specific genomic alterations influence the response to immunotherapy in these patients.
4c3880bb027f159e801041b1021e88e8 Result
Overall, 336 NSCLC patients underwent NGS on ctDNA. Of these 336 patients, 192 (57%) were females and 144 (43%) were males. The average age (range) was 64 (23-103) years. Clinical treatment information is currently available for 117 patients, of whom 50 (43%) received immune check-point inhibitors. Rates of stable disease, partial and complete responses (RECIST criteria), as well as progression-free survival and overall survival will be reported. In addition, to unravel the genomic determinants of response to immunotherapy we will use the blood-derived ctDNA to understand if hypermutated ctDNA is a predictive biomarker of response to immunotherapy.
8eea62084ca7e541d918e823422bd82e Conclusion
ctDNA collection was feasible in 336 patients. A prediction model to associate the ctDNA signature with response to immunotherapy based on plasma will be presented.
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