Virtual Library
Start Your Search
Rosa Alvarez
Author of
-
+
EP1.01 - Advanced NSCLC (ID 150)
- Event: WCLC 2019
- Type: E-Poster Viewing in the Exhibit Hall
- Track: Advanced NSCLC
- Presentations: 1
- Now Available
- Moderators:
- Coordinates: 9/08/2019, 08:00 - 18:00, Exhibit Hall
-
+
EP1.01-07 - Definitive Results of a Clinical and Molecular Multicentric Characterization of Long-Term Survivors with Advanced Non-Small Cell Lung Cancer (Now Available) (ID 1191)
08:00 - 18:00 | Author(s): Rosa Alvarez
- Abstract
Background
Long survivors (LS) in non-small-cell lung cancer (NSCLC), defined as an overall survival (OS) greater than 2 years, are less than 10% in most series. Classical prognosis factors include stage, weight loss and ECOG, but more information is missing in the literature. Recently, EGFR, ALK and ROS 1 population (less than 20%) reach OS longer than 2 years. Immunotherapy has demonstrated very promising results with more LS compared to chemotherapy in first and second line setting. In this study, we focused in the analysis of LS patients with advanced NSCLC EGFR wt (wild type) and ALK nt (non-translocated), defined as those with OS greater than 36 months, in 7 hospitals in Madrid.
Method
In this serie, first of all, we will try to make a clinical, histopathological characterization collecting data from clinical reports according to a previously defined information. In a second step, we will carry out a genetic analysis of these patient samples comparing to an opposite extreme short survivors (SS) samples (OS less than 9 months). Initially, we used a NGS method of RNA-seq technology to identify differentiating profiles of gene expression between the two opposite populations. And finally, we confirmed this preliminary profile by RT-PCR in the rest of samples.
Result
Ninety-six patients were initially included. The majority were men, smokers or former with adenocarcinoma and ECOG 0- 1. We have obtained a differential transcriptome expression between samples from 6 LS and 6 SS, resulting 13 over-expressed and 42 down-expressed genes in LS comparing to SS transcriptome expression. Some of the genes involved in this initial profile belong to different cellular pathways: Secretin Receptor, Surfactant Protein, Trefoil Factor 1, Serpin Family, Ca-bindings Protein channel and Toll like Receptor family. Finally, we carried on by RT-PCR in 40 samples of SS and LS survivors and only four genes were significantly down-regulated in SS compared to LS in the multivariate analysis. These 4 genes were related to Surfactant Proteins: SFTPA1 (p = 0.023), SFTPA2 (p = 0.027), SFTPB (p = 0.02) and SFTPC (p = 0.047)
Conclusion
We present a sequential genetic analysis of a LS population with NSCLC EGFR wt (wild type) and ALK nt (non-translocated), obtaining a differential RNA seq- and RT-PCR gene profile based on different surfactant proteins expression. A further confirmation in a larger sample is ongoing.
-
+
P2.14 - Targeted Therapy (ID 183)
- Event: WCLC 2019
- Type: Poster Viewing in the Exhibit Hall
- Track: Targeted Therapy
- Presentations: 1
- Moderators:
- Coordinates: 9/09/2019, 10:15 - 18:15, Exhibit Hall
-
+
P2.14-29 - Clinical Impact of Next-Generation Sequencing (NGS) in Blood Liquid Biopsies for Treatment Decisions in Advanced NSCLC (ID 2803)
10:15 - 18:15 | Author(s): Rosa Alvarez
- Abstract
Background
Blood-based NGS is emerging as either complementary or alternative to standard tissue genotyping in metastatic non-small-cell lung cancer (NSCLC). In cases where tissue is not enough to complete standard EGFR, ALK, and ROS1 testing, or when patients are tested as triple-negative for these genetic alterations, additional tumor genotyping can lead to the detection of further actionable mutations. Moreover, NGS provides valuable genomic information that could be used to select for immunotherapy in metastatic NSCLC.
We aimed to describe the molecular findings obtained by liquid biopsy of a cohort of advanced NSCLC patients with unknown/negative EGFR, ALK and ROS1 and how the results modified treatment decisions.
Method
We performed a retrospective study of advanced NSCLC patients that were analyzed with NGS as part of a molecular pre-screening for clinicals trials in our institution in Madrid (Spain) between October 2016 and March 2019. Patients >18 years-old, PS ECOG 0-2, stage IIIC-IV NSCLC were routinely tested for EGFR, ALK, and ROS1, in addition to PD-L1 (22C3). Those wild-type for EGFR, ALK, or ROS1, or without enough tissue to perform the triple testing were considered for blood-based NGS. The different diagnostic assays for ctDNA NGS used depended on clinical trial molecular pre-screening protocol: Foundation One® Liquid or Guardant360®.
We analyzed the frequency of oncogenic drivers, the proportion of patients treated with genotype-directed therapy, and survival.
Result
We analyzed 95 NSCLC pts with valid NGS results from ctDNA (blood sample).
We detected 14 oncogenic driver mutations (15%): 5 EGFR (5.2%), 1 ALK fusion (1%), 1 BRAF V600E (1%), 2 METex14 (2.1%), 2 RET fusion (2.1%) and 3 HER2 mutations (3.2%). We also found 16 KRAS mutations (16.8%), and genetic alterations in tumor suppressor genes: 39 TP53 (41%), and 6 NF1 mutations (6.3%).
So far 8/14 patients were treated with genotype-directed therapy (8.4%), 2 of them under clinical trial: 5 pts were treated with an anti-EGFR treatment, 2 pts received alectinib (1 pt for ALK rearrangement, 1 pt for RET rearrangement) and 1 pt with tepotinib (MET splice mutation)
Of the 6 patients with NF1 mutations, 4 pts were women (66%), 5 pts were current smokers (83%), median age at diagnosis was 69 years (66-80), and 5 pts had non-squamous histology (83%). PDL1 tumor expression was determined in 4 patients: 2 pts >50%, 1 pt 10%, and 1 pt 0%. NF1 was co-mutated in 4 pts with RAS (66%), 1 with both RAS and TP53, and 1 HER2 A775:G776insYVMA.
3/6 NF1 mutant patients were treated with single agent ICI: 2 pts with first-line pembrolizumab, and 1 pt second-line pembrolizumab. In addition, one patient with germline NF1 mutation was treated with 2nd line atezolizumab. All 3 pts obtained responded to ICI (1 pt with atypical response). We will present updated data on PFS and OS.
Conclusion
Blood-based NGS can guide treatment decisions in metastatic NSCLC, with special interest in those patients without enough tumor tissue, or wild-type to standard-tissue diagnostic tests. NF1 mutations in NSCLC could predict responses to immune-checkpoint inhibitors, and warrants further evaluation.
