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Carlos Vargas
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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): Carlos Vargas
- 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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P2.13 - Targeted Therapy (Not CME Accredited Session) (ID 962)
- 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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P2.13-11 - EGFR Amplification and Sensitizing Mutations Correlates with Survival from Erlotinib in Lung Adenocarcinoma Patients (MutP-CLICAP¶) (ID 14305)
16:45 - 18:00 | Author(s): Carlos Vargas
- Abstract
Background
Tumor heterogeneity causes different EGFR mutation abundances, and is believed to be responsible for varied progression-free survival (PFS) in lung adenocarcinoma (ADC) patients receiving EGFR-TKI treatment. EGFR amplification and its common presence in EGFR mutant allele might be determined by the EGFR copy number variation. Examination of EGFR amplification status in EGFR mutant patients could predict the efficacy of EGFR-TKI treatment
a9ded1e5ce5d75814730bb4caaf49419 Method
72 lung ADC patients, who harbored EGFR activating mutations and received erlotinib as first line treatment, were examined for EGFR amplification by FISH. We analyzed the relationship between the EGFR mutational status and copy number profile with clinical outcomes including response rate, overall-survival (OS), and PFS.
4c3880bb027f159e801041b1021e88e8 Result
Median age was 62-yo (r, 20-87 years), 53 patients were females (73%), and 89% had common mutations. Twenty-two (30.6%) samples with EGFR activating mutations were identified as having EGFR amplification. EGFR amplification was more frequent in patients with exon 19 deletion (p=0.05) and in those with better performance status (p=0.01). Patients with EGFR gene amplification had a significantly longer PFS than those without [(25.2 months, 95%CI 22.0-38.5) vs. (12.4 months, 95%CI 5.3-19.5); p=0.002] as well as better OS [(EGFR amplified 37.8 months, 95%CI 30.9-44.7) vs. (EGFR non-amplified 27.1 months, 95%CI 12.8-41.3); p=0.009]. EGFR amplification significantly influenced the response to erlotinib (p=0.0001).
8eea62084ca7e541d918e823422bd82e Conclusion
EGFR amplification occurs in one third of patients with lung ADC harboring EGFR activating mutations, and could serve as an indicator for better response and survival from EGFR-TKI treatment.
6f8b794f3246b0c1e1780bb4d4d5dc53
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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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P3.01-11 - Depression and Inflammation in Patients with EGFR-Mutated Non-Small Cell Lung Cancer (ID 14336)
12:00 - 13:30 | Author(s): Carlos Vargas
- Abstract
Background
Although depression appears to be associated with worse survival outcomes in cancer patients, the underlying mechanisms and basis of this association remain unknown. EGFR mutations have been associated with improved treatment response and prognosis in advanced non-small lung cancer (NSCLC). However, previous reports have described a positive association between this genotype and depression. This relationship could be at least partially explained by TNFa-mediated inflammation, which activates the hypothalamus-pituitary-adrenocortical (HPA) axis, leading to tryptophan depletion through the stimulation of indoleamine 2,3 dioxygenase.
a9ded1e5ce5d75814730bb4caaf49419 Method
32 patients diagnosed with metastatic NSCLC with an EGFR mutation were enrolled and followed monthly. In all cases patients were evaluated using the Self-rating depression scale (SDS) and the Numeric Rating Scale (NRS) in order to obtain a detailed evaluation of the initial symptoms and a qualitative assessment of the state of depression. In parallel we measured TNFa levels in serum/plasma (MaxDiscovery™ Human TNF-α ELISA Test Kit) upon receipt of genotype report, 4 and 12 weeks after initiating the targeted therapy, and at the time of progression. We examined differences between patients with and without depression with respect to the TNFa, as well as impact on various outcomes.
4c3880bb027f159e801041b1021e88e8 Result
Mean age was 58.9 years (+/- 12.4), 22 (68.8%) were women and 94% had an ECOG <2. Nineteen patients (59.4%) carried a del19, 8 (25%) had L858R, 2 (6.3%) L858R+T790M, 2 (6.3%) G719S and one patient had a del19+S768I (3.1%). Median follow-up was 15.4 months (95%CI 2.8-32.0), overall survival (OS) was 28.1 months (95%CI 25.5-30.6) and median progression-free survival (PFS) to first-line TKI was 13.1 months (95%CI 9.6-16.6).37.5% (n=12) of patients self-reported depression; in 25, 9.4 and 3.1% the clinical manifestations were mild (SDS 50-59; supportive psychotherapy), moderate (SDS 60-69; requirement of antidepressants) and severe (SDS 70 and above; required hospitalization). Depression was significantly associated with moderate-to-severe basal dyspnea (p=0.043), with brain metastases (p=0.003), and poor performance status (p=0.021). The average TNF at the time of genotype report was 12.2 pg/mL (SD±4.1), and was significantly higher in those who manifested depression (p=0.03). TNF levels increased 11% at 4 weeks and 75% at 12 weeks. Depression did not influence OS or first-line PFS.
8eea62084ca7e541d918e823422bd82e Conclusion
Mild to moderate depression is prevalent in patients with lung cancer harboring EGFR mutations. As previously reported, TNFa levels are elevated in patients with lung cancer and depression, particularly in the first 12 weeks post-treatment, a finding attributable to inflammation.
6f8b794f3246b0c1e1780bb4d4d5dc53
