Virtual Library
Start Your Search
Luis E Raez
Author of
-
+
MA19 - Genomic Markers of IO Response (ID 922)
- Event: WCLC 2018
- Type: Mini Oral Abstract Session
- Track: Immunooncology
- Presentations: 1
- Moderators:
- Coordinates: 9/25/2018, 15:15 - 16:45, Room 201 BD
-
+
MA19.06 - Blood Based Biomarkers: RNA, KRAS and PD-L1 Strongly Matching with Tissue and Showing Correlation with Clinical Responses In NSCLC Patient’s (ID 12358)
15:45 - 15:50 | Presenting Author(s): Luis E Raez
- Abstract
- Presentation
Background
Circulating cell-free tumor RNA (cfRNA) can be now safety isolated as cfDNA and used to measure changes in the tumor burden in the blood and changes in gene expression in non-small cell lung cancer (NSCLC) patients (pts). We are correlating these changes in cfRNA and PD-L1 with clinical response to therapy (chemotherapy, immunotherapy (IMMUNO) or targeted therapy) in stage IV NSCLC pts. Our group has been the first one to use cfRNA to detect PD-L1.
a9ded1e5ce5d75814730bb4caaf49419 Method
Blood was drawn from 31 pts under various treatments (tx) every 6-8 weeks, at the same time that CT scans were done. CfRNA was extracted from the resulting plasma and reverse transcribed with random hexamers to cDNA. Levels of cfRNA were quantitated by RT-qPCR and correlated with pts clinical response (CR/PR/SD/PD), as determined by CT scans.
4c3880bb027f159e801041b1021e88e8 Result
A total of 31 lung cancer pts were enrolled in a 2-year clinical study. 25 of 31 pts completed already the first two cycles of tx and had CT scans done. Of these, 6/8 pts with progressive disease (PD) showed increased (INC) levels of cfRNA, 9/13 pts with stable disease (SD) showed either no change (NC) or decreased (DEC) cfRNA, and 4/4 pts with partial response (PR) had NC or DEC cfRNA, corresponding to 76% concordance between cfRNA and clinical responses. PD-L1 expression measured in plasma cfRNA matched the tissue expression in 7/10 pts. In the one pt where PD-L1 was (-) in blood and (+) in tissue there was PD on IMMUNO. Among 8 pts treated with IMMUNO: 3/3 pts with PD showed INC PD-L1 cfRNA expression, 3/3 pts with SD had NC in negative PD-L1 status, and 2 pts with PR showed DEC PD-L1 cfRNA, corresponding to 100% correlation between PD-L1 expression levels and pt response. Of the 31 pts, 32% (10/31) harbored KRAS mutations in cfDNA. Of those with KRAS+ status by tissue-based testing, 83% matched with cfDNA results. Among KRAS+ pts, 80% (8/10) showed PD-L1 cfRNA expression in same blood draws with KRAS+ cfDNA, suggesting correlation between these cfDNA and cfRNA analyses.
8eea62084ca7e541d918e823422bd82e Conclusion
Significant association was observed between clinical response and changes in plasma cfRNA levels in NSCLC pts (76%). There was concordance between tissue- and blood-based testing in both DNA (KRAS mutations, 83%) and RNA (PD-L1 expression, 70%). While on IMMUNO levels of PD-L1 expression could be used to monitor response to immunotherapy.
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.
-
+
OA05 - Clinical Trials in IO (ID 899)
- Event: WCLC 2018
- Type: Oral Abstract Session
- Track: Advanced NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 9/24/2018, 13:30 - 15:00, Room 106
-
+
OA05.01 - Efficacy/Safety of Entinostat (ENT) and Pembrolizumab (PEMBRO) in NSCLC Patients Previously Treated with Anti-PD-(L)1 Therapy (ID 12922)
13:30 - 13:40 | Author(s): Luis E Raez
- Abstract
- Presentation
Background
Treatment options are limited for lung cancer patients whose disease has progressed on anti-PD-(L)1 therapy. HDAC inhibitors may synergize with PD-(L)1 inhibition to overcome resistance. We report the interim results of a Phase 2 trial of entinostat (ENT), a class I selective histone deacetylase (HDAC) inhibitor, plus pembrolizumab (PEMBRO) in patients with NSCLC previously treated with anti-PD-(L)1 therapy.
a9ded1e5ce5d75814730bb4caaf49419 Method
ENCORE-601 is an open-label study evaluating the combination of ENT + PEMBRO in patients with recurrent or metastatic NSCLC and prior progression on anti-PD-1/PD-L1 therapy. Patients were eligible irrespective of histology or baseline PD-L1 expression. Patients were treated with ENT 5 mg PO weekly and PEMBRO 200 mg IV Q3W. The primary endpoint was ORR as assessed by irRECIST. Tumor biopsies and blood samples for immune correlates were taken prior to and during treatment in a subset of patients. A total of 70 patients will be enrolled.
4c3880bb027f159e801041b1021e88e8 Result
Of 57 patients with anti-PD-(L)1 resistant/refractory NSCLC, the confirmed objective response rate with ENT + PEMBRO was 11% (6 of 57, 95% CI: 4-21%). Of 49 patients with post-baseline tumor measurements, 47% had at least some reduction in tumor. Anti-PD-(L)1 therapy was the most recent line of therapy in 38 of 57 patients, and the median time from last dose of prior anti-PD-(L)1 to study entry was 67 days. The median duration of response with ENT + PEMBRO was 5 months, with the longest over 14 months. Of the 6 responders, four were PD-L1 negative at study entry. Response was associated with a higher median baseline level of peripheral classical monocytes (CD14+CD16-HLA-DRhi) with 16.9% of total live PBMCs in responders (n=6) compared to 8.2% in non-responders (n=45). 5 patients (8.8%) experienced Grade 3/4 related irAEs (2 events each of pneumonitis and colitis, 1 event of hyperthyroidism). In addition, 19 patients (33.3%) experienced other Grade 3/4 related AEs with only fatigue, anemia, hypophosphatemia, and hyponatremia occurring in more than 1 patient. Additional correlative analyses to identify biomarkers of response, including whole exome sequencing and RNAseq, are in progress.
8eea62084ca7e541d918e823422bd82e Conclusion
ENT + PEMBRO demonstrated anti-tumor activity and acceptable safety in patients with NSCLC who have progressed on prior PD-(L)1 blockade. Ongoing analysis of immune correlates may identify strategies for effective patient selection.
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.
-
+
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: 2
- Moderators:
- Coordinates: 9/25/2018, 16:45 - 18:00, Exhibit Hall
-
+
P2.15-07 - Lung Cancer in the Young (ID 14248)
16:45 - 18:00 | Author(s): Luis E Raez
- Abstract
Background
Lung cancer is the leading cause of cancer related death worldwide. Median age at diagnosis is 70 years. Its presentation in patients 40 or younger is uncommon and it has been proposed that maybe is a different disease due to its clinical characteristics and genetic makeup. There are a limited number of studies in this population and they report different clinico-pathological characteristics in comparison with older patients.
a9ded1e5ce5d75814730bb4caaf49419 Method
This is a retrospective analysis of patients 40 years or younger diagnosed with lung cancer between 2009 and 2015 at Instituto Nacional de Enfermedades Neoplasicas (INEN) in Lima, Peru. Patient characteristics such as age, sex, smoking history, family history, symptoms, histological type, stage at diagnosis, and overall survival were collected from clinical files.
4c3880bb027f159e801041b1021e88e8 Result
During the study period, we identified 2946 patients with lung cancer. Among these, 107 (3.63%) patients were 40 years or younger. Median age at diagnosis was 36 years and 58% of patients were female. Most patients (77.5%) lacked family history of cancer. A smoking history was present in 13.3% of patients and exposition to biomass fumes from inhouse cooking was reported in 16.3%. Mean time from onset of symptoms to diagnosis was 2 months. Frequent symptoms at diagnosis were cough (59.2%), weight loss (56.1%), chest pain (50%), dyspnea (44.2%), hemoptysis (18.4%) and fever (9.6%). Most patients (59.8%) had performance status (PS) of 1. Adenocarcinoma was the most histological type (64.5%), followed by not otherwise specified (NOS) lung cancer (13.1%), squamous carcinoma (10.3%) and neuroendocrine carcinoma (5.6%). Almost all patients (96.9%) had unresectable disease at diagnosis (7.3%, stage III; 89.6% stage IV). The median overall survival was 7 months (range 4.4 – 9.5).
8eea62084ca7e541d918e823422bd82e Conclusion
The proportion of young patients with lung cancer in our population is higher than that reported in the literature. Lung cancer in the young is mostly sporadic, more frequent in women and usually of adenocarcinoma type. Young patients tend to present with advanced disease at diagnosis, resulting in a very poor survival. The molecular characterization of this cohort of patients is ongoing.
6f8b794f3246b0c1e1780bb4d4d5dc53 -
+
P2.15-23 - Are there Ethnic Disparities in the Clinical Outcomes of Non-Small Cell Lung Cancer Hispanic Patients Treated with Immunotherapy? (ID 12359)
16:45 - 18:00 | Presenting Author(s): Luis E Raez
- Abstract
Background
Immunotherapy outcomes in non-small cell lung cancer (NSCLC) are widely available thanks to studies that got the approval of PD-1/PD-L1 inhibitors. However a careful review of ethnicity can find that most of the studies were done in Non-Hispanic White or Asian populations. There is little known about the outcomes in Hispanics (H). It is well known that Hispanics (H) in the US seem to have a lower age-adjusted mortality in NSCLC and have a different gene expression profile than NHW with higher prevalence of EGFR mutations.
a9ded1e5ce5d75814730bb4caaf49419 Method
We reviewed clinical outcomes in 216 H pts with NSCLC stage IV treated with atezolizumab, nivolumab or pembrolizumab at 4 large cancer centers (Memorial Cancer Institute, University of Miami and Moffitt Cancer Center all of them in Florida (US), and the National Cancer Institute in Peru. These patients have failed at least one line of chemotherapy previously. All of these patients did not have actionable genes (EGFR. ALK, ROS-1). We assessed overall response rate ORR (CR+PR) as main objective and disease control rate (DCR: ORR+SD), median PFS (progression free survival) & overall survival (OS) and PFS at 6m and 12m as secondary objectives.
4c3880bb027f159e801041b1021e88e8 Result
Most of the pts were males: 116 (54%), 82% adenocarcinomas and the median age was 65 years (range: 37-88y). The ORR was 16% and the DCR that shows the clinical benefit was 67%. ORR and DCR were similar in adenocarcinomas (20%/68%) and squamous cell carcinomas (17%/64%). The progression free survival (PFS) at 6 months (m) and 12m were 80% and 56% respectively. Median PFS 14.5m and median overall survival were 19m, respectively.
8eea62084ca7e541d918e823422bd82e Conclusion
ORR for NSCLC pts treated with immunotherapy is 16% in Hispanics treated at 4 cancer centers compared to an expected 20% ORR for NHW as reported in the literature. Therefore it appears that Hispanics might not have a benefit from immunotherapy to the extent that NHWs do. We need a larger cohort and prospective studies to validate these findings.
6f8b794f3246b0c1e1780bb4d4d5dc53
-
+
SH01 - Highlight of the Previous Day Sessions (ID 884)
- Event: WCLC 2018
- Type: Highlight of the Day Session
- Track:
- Presentations: 1
- Moderators:
- Coordinates: 9/25/2018, 07:00 - 08:00, Plenary Hall
-
+
SH01.04 - Advanced Lung Cancer (ID 14779)
07:36 - 07:48 | Presenting Author(s): Luis E Raez
- Abstract
- Presentation
Abstract not provided
Only 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.
