INTRODUCTION To address the lack of genomic data from Hispanic/Latino (H/L) patients with lung cancer, the Latino Lung Cancer Registry was established to collect patient data and biospecimens from these patients. METHODS This retrospective observational study examined lung cancer tumor samples from 163 H/L patients, and tumor-derived DNA was subjected to targeted-exome sequencing (>1000 genes, including EGFR, KRAS, STK11, and TP53) and ancestry analysis. Mutation frequencies in this H/L cohort were compared with those in a similar cohort of non-Hispanic white (NHW) patients and were correlated with ancestry, sex, smoking status, and tumor histology. RESULTS Among adenocarcinomas (n=120) in the H/L cohort, 31% had EGFR mutations, versus 17% in the NHW control group (p < 0.001). KRAS (20% vs. 38%; p=0.002) and STK11 (8% vs. 16%; p=0.065) mutations occurred at lower frequency, and mutations in TP53 occurred at similar frequency (46% vs. 40%; p=0.355) in H/L and NHW patients, respectively. Within the Hispanic cohort, ancestry influenced the rate of TP53 mutations (p=0.009) and may influence the rate of EGFR, KRAS, and STK11 mutations. CONCLUSIONS Driver mutations in H/L lung adenocarcinoma patients differ in frequency from those in NHWs associated with their Indigenous American ancestry. The spectrum of driver mutations needs to be further assessed in the H/L population.
When compared to prior reports, this study suggests a lower frequency of MSI among the Puerto Rican population. The higher prevalence of MLH1 mutations correlates with previous studies of protein expression among the Hispanic community including Colombian, Uruguay and Brazilian populations.
We report a patient with CS presenting with ganglioneuromatosis, benign breast mass and osteosarcoma, harboring a novel molecular alteration in PTEN which to our knowledge has not been previously reported.
Introduction: Hispanics are projected to constitute 23% of the U.S. population by 2050. However, large-scale sequencing projects, such as The Cancer Genome Atlas (TCGA), provide little information on this ethnic population. In fact, only seven out of over 500 lung adenocarcinoma tumors sequenced in the TCGA database are reported to be Hispanic. To address the lack of genomic data from Hispanic/Latino patients with lung cancer, the Latino Lung Cancer Registry was established to collect patient data and biospecimens from these patients. Methods: This retrospective observational study examined lung cancer tumor samples from 163 Hispanic/Latino patients, and tumor-derived DNA was subjected to targeted-exome sequencing (>1000 genes, including EGFR, KRAS, STK11, and TP53) and ancestry analysis. Mutation frequencies in this Hispanic/Latino cohort were compared with those in a similar cohort of non-Hispanic white (NHW) patients. Novel mutations in EGFR were functionally characterized, and mutation rates were correlated with ancestry, patient sex, smoking status, and tumor histology. Results: Among adenocarcinomas (n=120) in the Hispanic/Latino cohort, 31% had EGFR mutations versus 17% in the NHW control group (p < 0.001). The EGFR mutations in Hispanic/Latino patients included well-characterized activating mutations, such as L858R, and uncharacterized EGFR variants. A rare exon 19 mutation, W731R, was identified that conferred resistance to both erlotinib and AZD9291. KRAS (20% vs. 38%; p=0.002) and STK11 (8% vs. 16%; p=0.065) mutations occurred at lower frequency, and mutations in TP53 occurred at similar frequency (46% vs. 40%; p=0.355) in Hispanic/Latino and NHW patients, respectively. Within the Hispanic cohort, ancestry influenced the rate of TP53 mutations (p=0.009) and may influence the rate of EGFR, KRAS, and STK11 mutations. Conclusions: Driver mutations in Hispanic/Latino lung adenocarcinoma patients differ in frequency from those in NHWs associated with their Indigenous American ancestry. The spectrum of driver mutations needs to be further assessed in the Hispanic/Latino population. Citation Format: William D. Cress, Nicholas T. Gimbrone, Bhaswati Sarcar, Edna Gordian, Jason I. Rivera, Christian Lopez, Jamie K. Teer, Eric A. Welsh, Alberto A. Chiappori, Matthew B. Schabath, Gary W. Reuther, Pedro G. Santiago-Cardona. Somatic mutations and ancestry markers in Hispanic lung cancer patients [abstract]. In: Proceedings of the Tenth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2017 Sep 25-28; Atlanta, GA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2018;27(7 Suppl):Abstract nr PR03.
BackgroundNivolumab (NIV) is a monoclonal antibody for patients with pre-treated advanced nonsquamous non–small-cell lung cancer (NSCLC). It is necessary to evaluate the cost effectiveness of NIV versus docetaxel (DOC), taking into consideration the expression of programmed death ligand 1 (PD-L1).PurposeCost-effectiveness analysis from the payer’s perspective of NIV versus DOC in patient with nonsquamus NSCLC by expression of PD-L1 test (subgroups:<10% vs.≥10%).Material and methodsEfficacy data were obtained from the CheckMate-057 trial to model the incremental cost-effectiveness ratio (ICER) of NIV versus DOC:Difference of overall survival (OS) between NIV vs. DOC: PD-L1 expression ≥10%: 0.9 life years gained (LYG) and PDL1 expression <10%: −0.03 LYG.Drug costs were estimated considering manufacturing costs plus VAT (4%). NIV: mg/m2; DOC: mg/m2. An adult patient was considered (weight=70 kg; body surface: 1.7 m2) (total doses per administration: NIV: 210 mg; DOC: 127.5 mg). Total treatment costs were estimated with the median of the number of administrations received (NIV: six administrations; DOC: four administrations). Other costs were not considered.Time horizon considered: 1 year.Two different one-way sensitivity analyses were performed to test the robustness of the model. Scenario 1: Difference in OS variation was considered.Variations of ±20% OS were performed:PDL1 expression ≥10%. Interval considered: 0.792 LYG – 1.18 LYG.PDL1 expression <10%. Interval considered: −0.036 LYG – −0.024 LYG. Scenario 2: Cost mg variation was considered. Variations of ±25% were performed.Interval considered: €17.14/mg – €10.28/mg.ResultsTreatment total costs were: NIV: €17,274.60 and DOC: 1167.92€.The ICER observed in the subgroup with PD-L1 expression ≥10% was €16,269.37/LYG. Otherwise, the ICER estimated in patients with PDL1 expression <10% was €536,889.33/LYG.No relevant differences in ICER were observed after both one-way sensitivity analyses were performed (OS variation and cost mg variation).ConclusionNIV vs. DOC is cost effective in patients with non-squamous NSCLC with PD-L1 expression ≥10%, although ICER is high.NIV vs. DOC is not cost effective in patients with non-squamous NSCLC with PD-L1 expression <10%.Reference and/or Acknowledgements1. Borghaei H, Paz-Ares L, Horn L, et al. Nivolumab versus docetaxel in advanced nonsquamous non-small-cell lung cancer. N Engl J Med2015;373:1627–39.No conflict of interest
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