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Victoria M. Raymond
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MA23 - Early Stage Lung Cancer: Present and Future (ID 926)
- Event: WCLC 2018
- Type: Mini Oral Abstract Session
- Track: Treatment of Early Stage/Localized Disease
- Presentations: 1
- Moderators:
- Coordinates: 9/26/2018, 10:30 - 12:00, Room 105
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MA23.02 - Circulating Tumor DNA Analysis with a Novel Variant Classifier for Recurrence Detection in Resected, Early-Stage Lung Cancer (ID 13498)
10:35 - 10:40 | Author(s): Victoria M. Raymond
- Abstract
- Presentation
Background
ctDNA is a blood-based biomarker with promising potential in lung cancer for minimal residual disease (MRD) assessment and early detection of recurrence. However, data regarding feasibility are limited, especially for stage I-II disease.
a9ded1e5ce5d75814730bb4caaf49419 Method
We performed longitudinal plasma ctDNA profiling of early-stage lung cancer patients (pts) that underwent resection at MD Anderson Cancer Center from Apr 2016 to Jan 2017. Plasma ctDNA was analyzed from pre-operative and multiple post-operative time points until disease recurrence. ctDNA profiling was performed using a 30kb Digital Sequencing panel (Guardant Health) covering SNVs in 21 genes and indels in 9 genes that are commonly present in lung cancer. ctDNA profiles from ~30,000 lung cancer pts were used to train a classifier to exclude non-tumor related mutations.
4c3880bb027f159e801041b1021e88e8 Result
A total of 40 pts were included in this analysis, comprised of the first 17 pts with recurrence in the longitudinal study and 23 consecutive pts without recurrence. This cohort was primarily stage I and II (15 [38%], 16 [40%]). Histology included adenocarcinoma (29 [73%]), SCC (6 [15%]), and SCLC (2 [5%]). 58% had adjuvant therapy. Median follow-up was 17.7 (3.4 – 24.5) months and median time to recurrence was 7.1 (3.4 – 16.5) months in this selected cohort. At least one ctDNA alteration was detected in 55% (21/38) of pts with evaluable pre-op samples and in 22% (8/37) of pts at 4 weeks post-op. Presence of ctDNA at 4 weeks post-op heralded eventual recurrence with 43% sensitivity and 91% specificity (75% PPV, 73% NPV) and was significantly associated with worse recurrence free survival (p=0.022, HR 6.52; 95% CI 1.3 – 32.6), while also accounting for stage. In the absence of the variant classifier, an additional 7/37 pts had non-tumor alterations detected at 4 weeks post-op with a recurrence sensitivity and specificity of 57.1% and 69.6%. ctDNA was identified in 76% (13/17) of pts prior to or at the time of recurrence. The median interval between ctDNA detection and radiographic recurrence was 91 days.
8eea62084ca7e541d918e823422bd82e Conclusion
Detection of post-op ctDNA, as early as 4 weeks after resection of early-stage lung cancer, is associated with significantly increased risk of recurrence. Accurate detection of ctDNA in this MRD setting is enabled by a highly sensitive sequencing platform that incorporates a novel variant classifier to enhance clinical specificity.
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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): Victoria M. Raymond
- 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.
6f8b794f3246b0c1e1780bb4d4d5dc53
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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): Victoria M. Raymond
- 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.
6f8b794f3246b0c1e1780bb4d4d5dc53
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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 | Presenting Author(s): Victoria M. Raymond
- 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%
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-6.0%
9.6%
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- 9.6%
Immunotherapy + Chemotherapy
1.8%
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- 1.8%
0.6%%
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- 0.6%
Chemotherapy +/- Biologics
23.5%
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- 23.5%
6.5%
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- 6.5%
Targeted Therapy
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31.3%
+ 31.3%
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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.
6f8b794f3246b0c1e1780bb4d4d5dc53
