Virtual Library
Start Your Search
Andrés F. Cardona
Author of
-
+
MA08 - Clinical Trials in Brain Metastases (ID 906)
- Event: WCLC 2018
- Type: Mini Oral Abstract Session
- Track: Advanced NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 9/24/2018, 15:15 - 16:45, Room 203 BD
-
+
MA08.02 - Prophylactic Cranial Irradiation Reduces the Risk of Brain Metastases in High-Risk Lung Cancer Patients: EGFR and ALK Mutations (ID 13496)
15:20 - 15:25 | Author(s): Andrés F. Cardona
- Abstract
- Presentation
Background
Prophylactic Cranial Irradiation (PCI) is considered standard-of-care for small-cell lung cancer, due to consistent findings of a reduced risk of developing brain metastases (BM) and a survival benefit. The role of PCI for patients with Non-small cell lung cancer (NSCLC) is less well established, since a clear survival benefit has not been identified, although high-risk subgroups have been identified, including patients with driver mutations and with elevated carcinoembryonic antigen (CEA) levels.
a9ded1e5ce5d75814730bb4caaf49419 Method
We assessed the use of PCI compared to observation in patients with stage IV NSCLC (NCT01603849). PCI dose was set 25 Gy/10 f. An amendment to the original record was requested so that patients who received PCI after January 2016 had hippocampal sparing. Primary end point was Intracranial Progression-Free survival (IPFS), secondary was overall survival (OS).
4c3880bb027f159e801041b1021e88e8 Result
84 patients were included, 43 were randomized to observation and 41 to PCI. 83.3% had a driver mutation (DM). Baseline characteristics were well balanced among groups. Median IPFS was 21.0 months (95%CI 16.2-25.9). Factors which were independently, positively associated with IPFS included ECOG (p=0.012) and therapeutic arm (p=0.006). PCI was associated with lower odds of progression to CNS (OR:0.16 (0.04–0.53), p=0.006).Cumulative incidence of BM at 1-yr was higher among patients without PCI (22% vs. 3%, p<0.001). Relative risk for IPFS in patients with DM was 0.29 (0.10-0.82, p=0.01), HR for OS was 0.48 (0.20-1.16, p=0.098). Median OS was higher in the PCI group compared to control [42.8 (95%CI: 28.1–57.6) vs. 25.9 (95%CI: 17.7 – 34.2)] months. Last, PCI was associated with lower hazards of death, 0.47 (0.24–0.95), p=0.035.
8eea62084ca7e541d918e823422bd82e Conclusion
PCI significantly increases IPFS and decreases risk of death in patients with advanced NSCLC, without neurocognitive impairment or decreased QoL. This intervention appears to be particularly useful for patients with good performance status and driver mutations. PCI increased IPFS without neurocognitive impairment or decreased QoL.
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.
-
+
MA25 - Oligometastasis: Defining, Treating, and Evaluating (ID 929)
- Event: WCLC 2018
- Type: Mini Oral Abstract Session
- Track: Oligometastatic NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 9/26/2018, 13:30 - 15:00, Room 203 BD
-
+
MA25.10 - Complete Response by PET-CT After Radical Treatment in Oligometastatic Non-Small Cell Lung Cancer Predicts Longer Survival (ID 14232)
14:35 - 14:40 | Author(s): Andrés F. Cardona
- Abstract
- Presentation
Background
Evidence is rapidly accumulating for the use of radical treatment approaches for patients with oligometastatic Non-small cell lung cancer (NSCLC). Several limitations remain, however, to further strengthen the use of radical therapy as opposed to standard maintenance therapy, including a lack of robust markers to predict patient response. In this study, we assessed the utility of reaching a complete response (CR) by PET-CT in patients with oligometastatic disease after radical treatment (NCT02805530).
a9ded1e5ce5d75814730bb4caaf49419 Method
We included patients with stage IV NSCLC who presented with ≤5 synchronous, any-site metastases (oligometastatic disease) as assessed by PET-CT. Patients received 4 initial cycles of systemic treatment. Following, patients were evaluated by PET-CT and those with stable disease and partial response received radical treatment to the primary site and metastases (surgery, radiotherapy, chemotherapy plus radiotherapy, radiofrequency and SBRT alone or in any combination). Response to radical treatment was evaluated by PET-CT. Maintenance treatment was permitted.
4c3880bb027f159e801041b1021e88e8 Result
37 patients were included in the analysis. Mean age was 55.7. At diagnosis 43.2% of patients presented with CNS metastases. After 4 cycles of first-line therapy, 100% of patients received treatment to the primary site, while 83.8% also received therapy to metastases. Following radical treatment, 19 (51.4%) patients achieved a CR by PET-CT, while 18 (48.6%) had a partial response (NON-CR). Median PFS was 26.2 months (95%CI 12.2-40.1), and was positively affected by CR by PET-CT (NR vs. 14.3 [95%CI 11.9-16.7]; p<0.001). Median overall survival (OS) was NR. OS was also positively affected by CR by PET-CT (42-month survival: 82.5%±18 for CR vs. 34.4%±28 for NON-CR by PET-CT; p=0.01).
8eea62084ca7e541d918e823422bd82e Conclusion
Patients with oligometastatic NSCLC who undergo radical treatment and reach a CR by PET-CT show a significant improvement in survival outcomes. Our results suggest that CR by PET-CT could serve as a surrogate marker for prolonged survival in this patient su
6f8b794f3246b0c1e1780bb4d4d5dc53
bgroup.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.
-
+
P1.01 - Advanced NSCLC (Not CME Accredited Session) (ID 933)
- Event: WCLC 2018
- Type: Poster Viewing in the Exhibit Hall
- Track:
- Presentations: 1
- Moderators:
- Coordinates: 9/24/2018, 16:45 - 18:00, Exhibit Hall
-
+
P1.01-03 - Effect of Prophylactic Cranial Irradiation on Cognitive Function and QoL in NSCLC Patients at High Risk of Brain Metastases (ID 14166)
16:45 - 18:00 | Author(s): Andrés F. Cardona
- Abstract
Background
Up to 50% of NSCLC patients develop brain metastases (BM). Prophylactic Cranial Irradiation (PCI) is a potentially useful strategy to prevent this event, although its use remains controversial due to inherent risks. Therefore, actions such as dose adjustment for Whole Brain Radiotherapy (WBRT), or hippocampal-sparing techniques have been explored. We evaluated the impact of PCI on cognitive function and Quality of Life (QoL).
a9ded1e5ce5d75814730bb4caaf49419 Method
Within the clinical trial NCT01603849 we evaluated a total of 84 histologically-confirmed NSCLC patients with high risk of developing BM (adenocarcinomas harboring oncodrivers (EGFR or ALK) and/or carcinoembryonic antigen (CAE) level at diagnosis ≥20 pg/mL). Patients were randomized 1:1, 41 to receive PCI and 43 to observation. Cognitive function (CF) was evaluated before and after treatment and at 6, 9 and 12 months with Mini Mental State Examination (MMSE). Reliable Change Index was used to evaluate the effect on CF. QoL was assessed through the European Organization for Research and Treatment of Cancer (EORTC-QLQ-30). Differences between groups were compared with Mann Whitney U and Friedman test. OS was estimated from the first MRI assessing the absence of BM until death/last follow-up with Kaplan-Meier and compared with Log-Rank test.
4c3880bb027f159e801041b1021e88e8 Result
83.3% of patients presented an EGFR-mutation (n=60) or ALK-rearrangement (n=6). Median OS was 42.8 vs. 25.9 months among patients with or without PCI (p=0.031). MMSE scores and median score values for global QoL, fatigue and cognitive functioning did not differ among groups or at baseline and follow-up. There were also no differences in percentual change at 1-yr (Table).
8eea62084ca7e541d918e823422bd82e ConclusionClinical changes (MMSE)
3 months
6 months
9 months
1 yr
n/N (%)
n/N (%)
n/N (%)
n/N (%)
Without PCI
Without Changes
38/43 (88.4)
34/42 (81)
34/42 (81.0)
29/37 (78.4)
Cognitive Deterioration
0/43 (0)
2/42 (4.8)
0/42 (0)
0/37(0)
Cognitive Improvement
5/43 (11.6)
6/42 (14.2)
8/42 (19.0)
8/37 (21.6)
With PCI
Without Changes
39/41 (95.1)
31/34 (91.2)
31/34 (91.2)
27/31(87.1)
Cognitive Deterioration
1/41 (2.4)
0/34 (0)
0/34 (0)
1/31(3.2)
Cognitive Improvement
1/41 (2.4)
3/34 (8.8)
3/34 (8.8)
3/31 (9.7)
Baseline
3 months
6 months
9 months
1 yr
p-Value (*)
Diff. at 1 yr
Median (IQR)
Median (IQR)
Median (IQR)
Median (IQR)
Median (IQR)
Median (IQR)
Global QoL
Without PCI
66.7 (50.0 - 83.3)
66.7 (50.0 - 83.3)
66.7 (64.6 - 83.3)
83.3 (66.7 - 85.4)
83.3 (75.0 - 87.5)
<0.001
8.3 (0.0 - 29-2)
With PCI
66.7 (50.0 - 83.3)
66.7 (50.0 - 83.3)
66.6 (66.7 - 83.3)
83.3 (66.7 - 83.3)
83.3 (75.0 - 83.3)
<0.001
0.0 (0 - 25.0)
p-Value (diff between groups)
0.956
0.786
0.903
0.172
0.595
0.791
Fatigue
Without PCI
22.2 (11.1 - 44.4)
33.3 (22.2 - 44.4)
22.2 (11.1 - 44.4)
22.2 (11.1 - 44.4)
22.2 (11.1 - 33.3)
<0.001
0.0 (-22.2 - 0.0)
With PCI
22.2 (5.6 -33.3)
33.3 (11.1 - 33.3)
22.2 (8.3 - 33.3)
22.2 (8.3 - 33.3)
22.2 (0.0 - 33.3)
<0.001
0 (0 - 0)
p-Value (diff between groups)
0.493
0.132
0.942
0.931
0.93
0.553
Cognitive
Without PCI
83.3 (66.7 - 100.0)
83.3 (66.7 - 100.0)
83.3 (66.7 - 100.0)
73.3 (83.3 - 100.0)
73.3 (83.3 - 100.0)
0.004
0 (0 - 0)
With PCI
83.3 (66.7 - 100.0)
83.3 (66.7 - 100.0)
83.3 (66.7 - 100.0)
91.7 (70.8 - 100.0)
83.3 (83.3 - 100.0)
0.017
0.0 (0.0 - 0.0)
p-Value (diff between groups)
0.854
0.983
0.521
0.411
0.757
0.734
PCI was not associated with significant differences in MMSE and QoL scores, furthermore there were no differences when assessing specific subscales (e.g. fatigue and cognitive functioning). These results along with the clinical benefit in OS highlight the benefit of this approach particularly among patients at high risk of developing BM.
6f8b794f3246b0c1e1780bb4d4d5dc53
-
+
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
-
+
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): Andrés F. Cardona
- 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
-
+
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
-
+
P1.13-01 - Anti-EGF Antibodies Increase the Effect of ALK and MEK Inhibitors in ALK and KRAS NSCLC and CRC Cell Lines (ID 13160)
16:45 - 18:00 | Author(s): Andrés F. Cardona
- Abstract
Background
Immunization against Epidermal Growth Factor (EGF) has demonstrated efficacy in a phase III trial including unselected NSCLC patients, and we have recently shown that antibodies generated by vaccination (anti-EGF VacAbs) potentiate the effects of TKIs in EGFR-mut cells growing in vitro. In this study, we aimed to determine if anti-EGF VacAbs show antitumor activity in KRAS-mutant (mut) and Anaplastic Lymphoma Kinase (ALK) translocated non-small cell lung cancer (NSCLC) and colorectal cancer (CRC) cells, alone or in combination.
a9ded1e5ce5d75814730bb4caaf49419 Method
Anti-EGF VacAbs were generated in rabbits. Cell lines were treated with anti-EGF VacAbs alone and in combination with ALK TKIs, trametinib and standard chemotherapeutic agents in ALK translocated (H3122, E13;A20 (v1) and H2228, E6;A20 (v3)) and lung (A549 and H23) and colon (DLD1 and LS174T) KRAS-mut cell lines. Cell viability was analyzed by MTT, changes of total and phosphorylated proteins by Western blot and emergence of resistance by direct microscopic examination in low density cultures.
4c3880bb027f159e801041b1021e88e8 Result
Anti-EGF VacAbs suppressed EGF-induced cell proliferation and inhibited EGFR phosphorylation signaling in all cell lines tested. In combination, the anti-EGF VacAbs significantly enhanced the antitumor activity of alectinib and crizotinib in H2228 cells and trametinib in A549, H23 and DLD1 cells. In these cell lines, the antibodies decreased Erk ½ and Akt phosphorylation. Finally, the addition of the anti-EGF VacAbs to the culture medium significantly delayed the emergence of resistant clones to alectinib and crizotinib in H2228 cells. In previous experiments, H2228 cells had shown a stronger dependency on the EGF/EGFR pathway than H3122. Results for the combination with standard chemotherapy in KRAS-mut cell lines will be presented at the meeting.
8eea62084ca7e541d918e823422bd82e Conclusion
Anti-EGF VacAbs decreased cell proliferation and inhibited EGFR activation in lung and colon ALK translocated and KRAS-mut cell lines. In addition, they potentiated the effects of trametinib in KRAS-mut cells and TKIs in ALK translocated cells (v3), where they also prevented the emergence of resistance to alectinib and crizotinib. Two clinical trials are currently testing anti-EGF vaccination in advanced NSCLC; the Epical Phase I/II trial, in combination with EGFR TKIs in EGFR-mut patients; and the BV-NSCLC-002 Phase III trial, in combination with chemotherapy in EGFR-wt.
6f8b794f3246b0c1e1780bb4d4d5dc53
-
+
P2.03 - Biology (Not CME Accredited Session) (ID 952)
- Event: WCLC 2018
- Type: Poster Viewing in the Exhibit Hall
- Track:
- Presentations: 1
- Moderators:
- Coordinates: 9/25/2018, 16:45 - 18:00, Exhibit Hall
-
+
P2.03-15 - Integrin-Linked Kinase (ILK), Protein Tyrosine Phosphatase SHP2 and B lymphoma Mo-MLV Insertion Region 1 Homolog (Bmi-1) in EGFR-Mutant NSCLC (ID 12557)
16:45 - 18:00 | Author(s): Andrés F. Cardona
- Abstract
Background
The clinical efficacy of EGFR tyrosine kinase inhibitors (TKIs) in EGFR-mutant non-small cell lung cancer (NSCLC) is jeopardized by the activation of multiple signaling pathways. ILK regulates the expression of Bmi-1, a well-known epithelial mesenchymal transition-inducing transcription factor. SHP2 function is required for MAPK pathway activation, and also plays a role in receptor tyrosine kinase signaling pathways.
a9ded1e5ce5d75814730bb4caaf49419 Method
Clinical data were assessed in accordance with the protocol approved by the institutional review board and de-identified for patient confidentiality. Pretreatment tumor specimens from advanced EGFR-mutant NSCLC patients (pts) were collected from eight sites in Spain, France, Italy and Colombia. mRNA gene expression analysis was performed by TaqMan (qRT-PCR). We examined the mRNA levels of ILK, SHP2 and Bmi-1.
4c3880bb027f159e801041b1021e88e8 Result
With a median follow-up of 26.7 months, median progression-free survival (PFS) was 9.3 (95% CI, 7.6-14.2) and 15.7 months (95%CI, 12.3-30.1) for pts with high and low ILK mRNA, respectively (P=0.0002), (HR for disease progression, 2.4; 95% CI, 1.3-4.5; P=0.002). Median PFS was 11.4 (95% CI, 8.2-14) and 24.1 months (95% CI, 8.2-30.9) for pts with high and low SHP2 mRNA, respectively (P=0.009), (HR, 2.4; 95% CI, 1.2-4.7; P=0.01). Median PFS was 8.2 (95% CI, 4.8-13.1) and 24.1 months (95% CI, 14.2-36.5) for pts with high and low SHP2 mRNA, respectively (P=0.001), (HR, 2.9; 95% CI, 1.4-5.9; P=0.002). Median overall survival (OS) was 17.9 (95% CI, 13.2-33) and 34.4 months (95% CI, 18.5-44.2) for pts with high and low ILK mRNA, respectively (P=0.200), (HR, 1.5; 95% CI, 0.79-3; P=0.200). Median OS was 18.5 (95% CI, 14-33) and 36.7 months (95% CI, 16.7-47.1) for pts with high and low SHP2 mRNA, respectively (P=0.018), (HR, 2.5; 95% CI, 1.1-5.8; P=0.020). Median OS was 17.6 (95% CI, 8.6-39.1) and 36.7 months (95% CI, 19.1-64.1) for pts with high and low Bmi-1 mRNA, respectively (P=0.004), (HR, 2.2; 95% CI, 1.0-5.1; P=0.040).
8eea62084ca7e541d918e823422bd82e Conclusion
The disturbance of RTKs, including ILK-SHP2-Bmi-1 axis, occurs frequently in EGFR mutant NSCLC patients, significantly limiting the PFS and OS. The levels of ILK, SHP2 and Bmi-1 could be predictive for upfront combinatory therapy of EGFR TKI plus a MAPK pathway inhibitor (SHP2 or MEK inhibitors).
6f8b794f3246b0c1e1780bb4d4d5dc53
-
+
P2.04 - Immunooncology (Not CME Accredited Session) (ID 953)
- Event: WCLC 2018
- Type: Poster Viewing in the Exhibit Hall
- Track:
- Presentations: 1
- Moderators:
- Coordinates: 9/25/2018, 16:45 - 18:00, Exhibit Hall
-
+
P2.04-01 - Associations Histological Subtype of Lung Adenocarcinoma and Programmed Death Ligand 1 (PD-L1) Expression in Tumor Cells. (ID 12995)
16:45 - 18:00 | Author(s): Andrés F. Cardona
- Abstract
Background
The analysis by immunohistochemistry (IHC) of the programmed cell death-ligand 1 (PD-L1) protein expression is the most extensively explored biomarker for response to immunotherapy in non-small cell lung cancer (NSCLC). However, there are differences concerning diverse IHC assays and cut-off criteria: Pembrolizumab with the 22C3 assay with cut-off ranges of >1%, 1-49% and >50%; and Nivolumab with the 28-8 assay and ranges of <1%, 1-5%, 5 -10% and >10%. Furthermore, there is lack of information regarding the association between the histological subtype of adenocarcinoma and PD-L1 expression. In this work, we assessed the frequency of PD-L1 expression according with to histological subtype of adenocarcinoma.
a9ded1e5ce5d75814730bb4caaf49419 Method
PD-L1 expression was assessed using the PD-L1 IHC 22C3 pharmDx immunohistochemistry assay (Dako North America, Inc.). We correlated histological subtype of adenocarcinoma with the frequency and intensity of PD-L1 expression, smoking history, EGFR and ALK status.
4c3880bb027f159e801041b1021e88e8 Result
Tissue samples from one hundred and sixty-two were analyzed, of which 33 (20.4%) were excluded due to insufficient material for PD-L1asessment. Among them, 106 patients (71,55%) were female, the median age was 63 years (range 31-86 years), 69 (53.5%) were never-smokers with no exposition to wood smoke or asbestos (79,61.2% and 117, 90.7% respectively). Among the 129 adenocarcinomas, 31.0% were acinar histological subtype; 27.1% solid, 17.1% papillary, 3.9% lepidic, 1.6% micropapillary and 54.3% had a moderated tumor differentiation grade. According to PD-L1 score, 49 (38%) of the patients were classified as negative (PD-L1<1%), 71(55%) as poor PD-L1 expression (1 - 49%), and 9 (7%) as strong PD-L1 expression (≥50%). According to the IASLC/ATS adenocarcinoma histological subtype was associated with PD-L1 expression (p=0.003). Solid and acinar adenocarcinomas were more likely to present strong PD-L1 expression (55.6% & 33.3%, respectively) compared to lepidic, papillary, micropapillary and unspecified tumors, which presented a strong PD-L1 expression in up to 11.1%. Median PFS to first line therapy was 10.3 (95% CI: 6.1–14.5) months. Tobacco exposure was the only factor independently associated with an increase in the hazard of progression to first line therapy (either CT or TKI) from any cause among NSCLC patients (HR, 95% CI: 1.56-12.1). The median OS was 41.9 (95% CI: 10.9–72.9) months. Median OS differences were not found among PD-L1 (negative vs. positive: 60.6 vs. 31.3 months, p=0.685).
8eea62084ca7e541d918e823422bd82e Conclusion
Patients with adenocarcinoma tumors, solid histological subtype and poor differentiation grade can be more benefited with a PD-1 based immunotherapy. PD-L1 score can be a predictor factor for the response to first line chemotherapy.
6f8b794f3246b0c1e1780bb4d4d5dc53
-
+
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
-
+
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 | Presenting Author(s): Andrés F. Cardona
- 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
-
+
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
-
+
P3.01-11 - Depression and Inflammation in Patients with EGFR-Mutated Non-Small Cell Lung Cancer (ID 14336)
12:00 - 13:30 | Presenting Author(s): Andrés F. Cardona
- 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
-
+
P3.04 - Immunooncology (Not CME Accredited Session) (ID 970)
- Event: WCLC 2018
- Type: Poster Viewing in the Exhibit Hall
- Track:
- Presentations: 1
- Moderators:
- Coordinates: 9/26/2018, 12:00 - 13:30, Exhibit Hall
-
+
P3.04-16 - A Seven-Gene Expression Signature Reveals Unique Immune-Phenotypes Related to Major Oncogenic-Drivers in NSCLC (ID 13991)
12:00 - 13:30 | Author(s): Andrés F. Cardona
- Abstract
Background
In oncogenic-driven non-small cell lung cancer (NSCLC), programmed death ligand 1 (PD-L1) expression is the result of a constitutive oncogenic activation leading to an immunosuppressive microenvironment. However, the relationship between the major driver mutations (KRAS, EGFR and ALK) and PD-L1 and other immune markers remains unclear. Gene expression signatures incorporating not only PD-L1 but also other components of the stroma might better capture the immune-context of these oncogenic subgroups.
a9ded1e5ce5d75814730bb4caaf49419 Method
A 7-gene ‘immune signature’ comprising CD4, CD8, PD-1, PD-L1, IFNG, GZMM and FOXP3 was included in a customized nCounter panel (NanoString Technologies), used in our clinical institution on a routine basis and designed to simultaneously screen for gene fusion drivers (ALK, ROS1, RET and NTRK1), MET overexpression and MET exon 14-skipping mutations in formalin-fixed paraffin embedded (FFPE) samples. A total of 296 advanced NSCLC patients from two different institutions were analyzed by the panel. Among them, 115 patients (38.9%) were also submitted to next-generation sequencing (NGS, Ion Torrent PGM® or GeneReader) . Analyses of variance (ANOVA) were used to describe statistical significance between immune response genes in the two major oncogenic groups: KRAS mutant (n=33) andALK rearranged (n=44), compared to wild-type (WT) tumor samples (n=38).
4c3880bb027f159e801041b1021e88e8 Result
Oncogenic genes (ALK, KRAS) were mutually exclusive. The analysis of the 7-gene signature revealed distinct expression patterns in the oncogenic biomarker groups. A significantly higher mRNA expression of CD4 and PD-L1 was found in ALK rearranged tumors compared to the KRAS mutant, and WT groups (p=0.0014 and p=0.0467, respectively). In addition, a trend was observed between GZMM mRNA levels and the oncogenic groups (p= 0.0665) whereas no association was found with the other immune genes (CD8, PD-1, IFNG, FOXP3). There was a significant linear correlation between CD4 and PD-L1 in ALK positive patients (p= 0.0214), but not in KRAS mutant samples (p= 0. 112). Unsupervised clustering across mRNA expression data from 296 samples using 7-immune-related genes showed two clusters, high expression for ALK-rearranged patients and low expression for KRAS mutant patients. The correlation between each of the immune genes was performed and a high correlation was found between PD-1 and FOXP3 (r=0.9) and PD-1 with GZMM (r=0.8).
8eea62084ca7e541d918e823422bd82e Conclusion
NSCLC tumors with ALK alterations show a distinct CD4 and PD-L1 immune profile when compared to KRAS and WT samples.
6f8b794f3246b0c1e1780bb4d4d5dc53
