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N. Peled
Moderator of
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Optimizing targeted therapy in lung cancer (ID 56)
- Event: ELCC 2018
- Type: Poster Discussion session
- Track:
- Presentations: 7
- Moderators:F. Cappuzzo, N. Peled
- Coordinates: 4/12/2018, 16:45 - 17:45, Room W
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Invited Discussant 3PD, 51PD and 132PD (ID 678)
16:45 - 17:45 | Presenting Author(s): F. Cappuzzo
- Abstract
- Presentation
Abstract not provided
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Invited Discussant 52PD and 133PD (ID 679)
16:45 - 17:45 | Presenting Author(s): N. Peled
- Abstract
- Presentation
Abstract not provided
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132PD - Plasma concentrations of pemetrexed to predict clinical outcomes in patients with advanced NSCLC (ID 614)
16:45 - 17:45 | Presenting Author(s): S. Visser | Author(s): S. Koolen, P. de Bruijn, R. Mathijssen, B. Stricker, J. Aerts
- Abstract
Background:
Currently, there are no clinically useful predictors of efficacy and toxicity to pemetrexed (PMX) in advanced non-small-cell lung cancer (NSCLC). Using population pharmacokinetic (pop-PK) modelling, we explored whether total exposure to PMX predicts for progression-free and overall survival (PFS/OS) and occurrence of (severe) chemotherapy (CTx)-related adverse events (AEs).
Methods:
In a prospective observational multi-center study, patients with stage IIIB/IV NSCLC receiving first- or second-line PMX(/platinum) were enrolled. PMX (500 mg/m[2]) was administered as a 10-min intravenous infusion every 21 days. Prior to and weekly after each PMX administration, plasma sampling was performed (cycle PK). In a subgroup, blood samples were also collected at 10, 30 minutes and 1, 2, 4, 8, 24 hours after start of PMX infusion (24h PK). With pop-PK modelling total exposure (AUC) to PMX per patient was estimated. The relation between AUC during cycle 1 (AUC~1~) and OS/PFS in treatment-naïve patients was examined using Cox regression analyses and in all patients we compared the difference in mean AUC~1~ between patients with and without grade ≥3 CTx-related AEs (CTCAE 4.03) during total treatment of 4 cycles.
Results:
For 106 of the 165 patients, concentrations of PMX were quantified (24h PK, n = 15; cycle PK, n = 106). Median estimated AUC~1~ was 201 mg·h/L (interquartile range: 179–224). In treatment-naive patients (n = 95), AUC~1~ did neither univariably predict for OS/PFS, nor multivariably when adjusted for prognostic factors sex, disease stage and WHO performance score (OS, HR = 1.05, 95%CI: 1.00–1.11; PFS, HR = 1.03, 95%CI:0.98–1.08). Compared to patients without ≥ grade 3 CTx-related AEs (n = 51), patients with ≥ grade 3 CTx-related AEs (n = 55) had significantly higher AUC~1~ values (220 vs 191, p < 0.001). When seperating ≥ grade 3 CTx-related AEs into clinical and laboratory AEs, identical results were found.
Conclusions:
Total systemic exposure to PMX does not predict for PFS/OS, but is significantly associated with more frequent occurrence of severe CTx-related AEs. Although the impact of peak concentrations on efficacy remains unclear, our findings suggest that lower dosage might prevent severe toxicity with preservation of efficacy.
Clinical trial identification:
Legal entity responsible for the study:
Erasmus MC
Funding:
ZonMw
Disclosure:
J. Aerts: Member of Scientific Committee ELCC 2018; consultant/advisory role with Eli Lilly and Company. All other authors have declared no conflicts of interest.
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133PD - Adjuvant epidermal growth factor receptor tyrosine kinase inhibitors (EGFR TKIs) for non-small cell lung cancer (NSCLC): A systematic review and meta-analysis (ID 256)
16:45 - 17:45 | Presenting Author(s): J. Raphael | Author(s): M. Vincent, G. Boldt, P. Shah, G. Rodrigues, P. Blanchette
- Abstract
Background:
The role of adjuvant EGFR-TKIs in NSCLC is not well defined. Recently 2 randomized trials showed a significant disease free survival (DFS) benefit with the use of adjuvant TKIs compared to platinum-based chemotherapy in EGFR-mutant patients. Yet, older trials conducted on patients with any EGFR status did not demonstrate the same benefit. Herein, we conduct a systematic review and meta-analysis to assess the efficacy and safety of adjuvant TKIs in NSCLC patients.
Methods:
The electronic databases Medline (PubMed) and EMBASE were searched for relevant randomized trials between January 2000 and October 2017. Pooled hazard ratios (HR) for DFS and overall survival (OS), and pooled risk ratios (RR) and odds ratios (OR) for 2-year DFS and toxicity were extracted using the generic inverse variance and the Mantel-Haenszel and Peto method to perform a meta-analysis. To account for between-studies heterogeneity, random-effect models were used. Subgroup analyses assessed patients with a sensitizing EGFR mutation.
Results:
Six studies met the inclusion criteria and were included. In patients with any EGFR status, adjuvant TKIs marginally improved the DFS (5 trials, 1,860 participants, HR = 0.65, 95%CI 0.43–1.00) but not OS (4 trials, 662 participants, HR = 0.8, 95%CI 0.48–1.33). The risk of developing grade 3 or higher skin toxicity (6 trials, 1,831 participants, OR = 6.07, 95%CI 4.34–8.51) and diarrhea (6 trials, 1, 831 participants, OR = 4.05, 95%CI 2.44–6.74) was increased compared to chemotherapy, placebo or no treatment. In EGFR-mutant patients, adjuvant TKIs decreased the risk of disease recurrence by 48% (5 trials, 560 participants, HR = 0.52, 95%CI 0.35–0.78), improved the 2-year DFS (6 trials, 599 participants, HR = 0.53, 95%CI 0.43–0.66) but had no effect on OS (4 trials, 662 participants, HR = 0.64, 95%CI 0.22–1.89).
Conclusions:
Adjuvant TKIs significantly decrease the risk of recurrence in EGFR-mutant NSCLC patients but do not improve OS. Yet, OS data are still immature and longer follow up is needed for a definitive assessment of this outcome measure. Further results from ongoing well-designed trials will define the role of adjuvant TKI in NSCLC and provide stronger conclusions.
Clinical trial identification:
N/A
Legal entity responsible for the study:
Jacques Raphael
Funding:
Has not received any funding
Disclosure:
All authors have declared no conflicts of interest.
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3PD - Co-targeting PIM1 or Src to overcome the limits of single MET inhibition (ID 333)
16:45 - 17:45 | Presenting Author(s): I. Attili | Author(s): N. Karachaliou, J. Bracht, J. Berenguer, C. Codony-Servat, M. Ito, M. Rugge, P.F. Conte, L. Bonanno, R. Rosell
- Abstract
Background:
Single MET inhibition has controversial effects in MET addicted tumors. Proviral integration site for Moloney murine leukemia virus-1 (PIM1) is activated upon MET inhibition in MET addicted cells. PIM1 drives the expression of receptor tyrosine kinases (RTKs). SHP2, a non-receptor protein tyrosine phosphatase, is central in RTKs signaling and in Src activation. We have shown that the overexpression of RTKs like AXL and the transmembrane protein CUB domain-containing protein-1 (CDCP1) as well as Src activation, are mechanisms of intrinsic resistance to EGFR inhibition in EGFR mutant lung cancer. We are now testing whether RTKs, SHP2 or CDCP1 expression and activation are driven by PIM1 or Src and cause resistance to MET inhibitors in MET addicted tumors.
Methods:
We studied the inhibitory effect of the class I MET inhibitors tepotinib and savolitinib, the pan-PIM inhibitor AZD1208, and the Src inhibitor dasatinib in five MET addicted cell lines: 2 MET amplified lung cancer cells (EBC1 and H1993), 2 MET exon 14 mutant cells (Hs746T and H596) and a glioma cell line that carries the still not well recognized MET exon 7–8 splicing variant (E98). We assessed the effect of combined MET and PIM or MET and Src inhibition in cell viability and protein immunoblotting.
Results:
All the cell lines were sensitive to single MET inhibition (except H596) and resistant to single AZD1208 or dasatinib. The combination of savolitinib or tepotinib with AZD1208 was synergistic in the EBC1 cell line and slightly synergistic or additive in the H1993, Hs746T and E98 cell lines. The combination of savolitinib or tepotinib with dasatinib was highly synergistic in all four cell lines. The treatment of EBC1 cells with tepotinib monotherapy was not able to inhibit AXL activation while it induced the activation of SHP2 and CDCP1. AXL, CDCP1 and SHP2 expression or activation were downregulated when tepotinib was combined with dasatinib.
Conclusions:
Co-targeting PIM or Src with MET can be more effective than MET inhibition alone in MET addicted cell lines. Overexpression and activation of RTKs, CDCP1 and SHP2 can be mechanisms of resistance to single MET inhibition. The investigation of combinatorial strategies in MET addicted tumors, merits further investigation.
Clinical trial identification:
Legal entity responsible for the study:
IGTP – Germans Trias i Pujol Research Institute, Badalona, Barcelona, Spain
Funding:
Fundació Obra Social “La Caixa”
Disclosure:
All authors have declared no conflicts of interest.
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51PD - Effect of MEK inhibition on PDL1 and and on cytokinesproduction profilein NSCLC cell lines and in human lymphocites (ID 535)
16:45 - 17:45 | Presenting Author(s): F. Morgillo | Author(s): C.M. Della Corte, G. Viscardi, R. Di Liello, F. Papaccio, F. Ciardiello
- Abstract
Background:
Preclinical models suggest that MAPK pathway is implicated in the immune-resistance of tumors and MEK-inhibition can increase the CD8+ T-cell infiltration and the efficacy of PD-1/PD-L1 blockade.
Methods:
First, we evaluated PD-L1 mRNA expression by Real Time qPCR and its protein production, togheter with MAPK proteins in a panel of non-small cell lung cancer (NSCLC) cell lines. Then, we studied the changes in PD-L1 and major histocompatibility complex class-I (MHC-I) expression and cytokines’ production, after inhibition with selumetinib or stimulation of MAPK signalling by phorbol 12-myristate 13-acetate (PMA). In addition, we explored the effect of MEK inhibition on T-cell function by using Peripheral blood mononuclear cells (PBMC) from healthy volunteers.
Results:
A consistent correlation between PD-L1 mRNA and protein expression across cell lines suggested that expression mainly depends on trascriptional regulation, and it is regulated by MAPK signal, through the bindng of p65 to the PD-L1 promoter. Moreover, MEK inhibition resulted in an increased expression of MHC-I on cancer cells and increased mRNA expression levels of IFN gamma, IL-6, IL-1B, and TNFalpha, all molecules involved in the activation and differentiation of TCD8+ cytotoxic lymphocytes (CTL) subset. In this scenario, we also tested the effect of MEK inhibitor on activated T-lymphocytes from PBMC of healthy volunteers. After five days of treatment, RT-qPCR analysis revealed a significant increase of mRNA expression of some typical CD8+ T cell pro-inflammatory cytokines, like IL-12, TNFalpha and IFNgamma.
Conclusions:
These results further support the idea that MEK inhibitor reduces PD-L1 expression and this allows the establishment of a pro inflammatory microenvironment. On the other side, pheripheral T cells, treated with selumetinib, produce pro inflammatory cytokines typical of CTL subset, that seems more involved in immune response against cancer. In this context, MEK inhibition may represent a potential mechanism to convert otherwise resistant cancers and suggest new potential treatment combination strategies of MEK-inhibitors with anti-PD-L1 antibodies in NSCLC.
Clinical trial identification:
Legal entity responsible for the study:
University of Campania “L. Vanvitelli”
Funding:
Has not received any funding
Disclosure:
All authors have declared no conflicts of interest.
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- Abstract
Background:
TKI has significantly improved survival time of NSCLC pts with sensitive mutation. However, pts present different outcome while receiving TKI treatment. We conduct a prospective multicenter clinical trial to determine whether clonality of sensitive mutation is related to the efficacy of TKI. We also evaluate the consistency of TMB between tissue and blood in this cohort.
Methods:
Paired tumor and plasma samples at diagnosis were obtained from systemic treatment naïve pts with advanced NSCLC. DNA was sequenced by target-capture deep sequencing of 1021 previously annotated genes related to solid tumors. Clonal EGFR mutation was defined if EGFR mutation was in the cluster with the highest mean variated allele frequency with PyClone, and otherwise subclonal EGFR mutation. TMB of tissue (tTMB) and blood (bTMB) analysis interrogated single nucleotide variants, small insertion and deletion, with VAF ≥3% and ≥0.5%, respectively. TMB-high pts were identified with ≥9 mut/MB (upper quartile of data from geneplus).
Results:
During February to November 2017, 80 advanced NSCLC pts were enrolled from 9 centers. A total of 371 somatic variations were detected in tissues. Mutations occurred most frequently in TP53 (52%), EGFR (47%), ALK (13%), KRAS (11%). In matched plasma, 258 (70%) tumor-derived mutations were detected by pan-caner panel sequencing. A total of 41 EGFR mutations were detected in 37 pts, most of which occurred in tyrosine kinase domain (Ex19del, 42%; L858R, 37%). Most EGFR mutation were clonal in tissue and plasma, with a consistence of 85% in paired samples. In addition, bTMB was significantly correlated to tTMB (Pearson r = 0.75, p-value = 2.3e-12), with a consistence of 90%. Interestingly, high TMB was observed in a small fraction of patients (6%) with driver mutations, such as mutations in EGFR, ALK fusion, ERBB2 and PIK3CA.
Conclusions:
Deep sequencing with the pan-cancer panel can effectively detect mutations and evaluate TMB in both tissue and blood with high consistence. EGFR mutations can be clonal or subclonal in both tissue and blood. Prospective multicenter study is ongoing to determine the EGFR clonality as a predictive factor for the TKI efficacy in NSCLC (TRACELib-NSCLC).
Clinical trial identification:
NCT03059641
Legal entity responsible for the study:
Shanghai Chest Hospital
Funding:
Geneplus-Beijing Institute
Disclosure:
All authors have declared no conflicts of interest.
Author of
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Keynote lecture (ID 30)
- Event: ELCC 2018
- Type: Keynote Lecture
- Track:
- Presentations: 1
- Moderators:P. Van Schil
- Coordinates: 4/14/2018, 08:45 - 09:15, Room A
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Early detection of lung cancer (ID 122)
08:45 - 09:15 | Presenting Author(s): N. Peled
- Abstract
- Presentation
Abstract not provided
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Optimizing targeted therapy in lung cancer (ID 56)
- Event: ELCC 2018
- Type: Poster Discussion session
- Track:
- Presentations: 1
- Moderators:F. Cappuzzo, N. Peled
- Coordinates: 4/12/2018, 16:45 - 17:45, Room W
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Invited Discussant 52PD and 133PD (ID 679)
16:45 - 17:45 | Presenting Author(s): N. Peled
- Abstract
- Presentation
Abstract not provided
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Poster Display session (Friday) (ID 65)
- Event: ELCC 2018
- Type: Poster Display session
- Track:
- Presentations: 5
- Moderators:
- Coordinates: 4/13/2018, 12:30 - 13:00, Hall 1
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10P - The micro-environmental cross talk between mast cells and lung cancer cells through cell-to-cell contact (ID 170)
12:30 - 13:00 | Author(s): N. Peled
- Abstract
Background:
Mast cells (MCs) are key effectors in allergic reactions, but are also involved in tissue remodeling, wound healing and protection against pathogens. MCs infiltrate tumors and their number within the tumor microenvironment in certain cancer types, such as lung cancer, has been correlated with poor prognosis. The nature of crosstalk between lung cancer and MCs remains poorly resolved. In this study, we investigated the activation patterns within the MCs following cell-to-cell contact with lung cancer cells.
Methods:
Human MCs (HMC-1 and LAD-2) were exposed to Human lung cancer cell (H1299) derived membranes to recapitulate cell contact mediated activation. Lysates of MCs were tested for protein expression and posttranslational modifications (i.e. phosphorylation) by targeted western blotting. We unraveled the intracellular signaling molecules that are necessary for this signaling pathway by a pharmacological approach using several inhibitors. Each treatment was repeated at least 3 times.
Results:
H1299 membrane exposure activated the ERK1/2 MAP kinases in HMC-1 and in LAD-2 cells. AKT signaling was also activated in LAD-2 cells as a result of this contact. Furthermore, we discovered that inhibition of protein kinase C (PKC) augments the activation of ERK1/2 in LAD-2 cells, while it inhibits ERK1/2 activation in HMC-1 cells. Activation of AKT is inhibited by PI3K and PKC inhibitors.
Conclusions:
Our results suggest that H1299 membranes activate ERK1/2 in MCs. In addition, we discovered that there is an important difference between ERK1/2 MAP kinase signal transduction in HMC-1 and LAD-2 cells, whereby PKC is an inhibitor of the H1299 stimulated activation of ERK1/2 in LAD-2 cells, while it mediates ERK 1/2 activation in HMC-1 cells. Furthermore, we can conclude that H1299 membranes activate AKT and that the activation is mediated by PI3K and PKC. Rachel Shemesh and Yaara Gorzalczany contributed equally to this work. Correspondence Authors: Nir Peled, Ronit Sagi-Eisenberg.
Clinical trial identification:
Legal entity responsible for the study:
Prof. Nir Peled, Prof. Ronit Sagi-Eisenberg
Funding:
Has not received any funding
Disclosure:
All authors have declared no conflicts of interest.
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145P - Impact of next-generation sequencing on survival in lung cancer (ID 595)
12:30 - 13:00 | Author(s): N. Peled
- Abstract
Background:
Next-generation sequencing (NGS) enables a comprehensive genomic analysis of lung cancer patients. It has uncovered many novel genetic abnormalities and identified actionable genomic alterations in lung tumors that previously tested “negative” by conventional non-NGS tests. In this study, we evaluated the clinical impact of NGS on overall survival of advanced non-small cell lung cancer (NSCLC) patients.
Methods:
In this retrospective study, 234 consecutive stage IIIb/IV NSCLC patients who performed hybrid capturing NGS were enrolled in Israel, between 2011–2017. Hybrid capture-based NGS was performed by Foundation Medicine and Guardant 360[TM] if tissue was not available.
Results:
234 consecutive NSCLC patients were included in this study. 62% (145/234) performed tissue NGS and 38% (89/234) performed liquid NGS. Median age at diagnosis was 63 years. 84% had adenocarcinoma. 37% were never-smokers. The patients were divided into 4 groups according to the identification of NCCN-approved actionable genomic alterations on NGS analysis: Group A did not have an actionable target; Group B discovered an actionable target but did not receive targeted treatment, due to high performance status or preference to use immunotherapy for PD-L1 positive patients; Group C received targeted therapy subsequent to NGS analysis, among them 75 received treatment according to NCCN guidelines, 9 off-protocol and 7 received immunotherapy due to high tumor mutation burden found on NGS analysis; Group D received targeted therapy due to standard molecular tests, as PCR, IHC and FISH performed prior to NGS. Median Overall survival (OS) is summarized in the Table (p = 0.0278).Table: (Abstract 145P)Overall SurvivalTotal Cohort (n = 234) Group A 46% (108/234) Group B 5.5% (13/234) Group C 39% (91/234) Group D 9.5% (22/234) Median OS 20.9 months (95% CI: 19.0–28.7) 17.8 months (95% CI: 13.1–24.2) 10.8 months (95% CI: 4.1–NA) 25.7 months (95% CI: 19.9–41.7) 37.7 months (95% CI: 26.7–NA)
Conclusions:
This study evaluates the clinical impact of comprehensive NGS testing by demonstrating the survival advantage of patients with actionable targets discovered through NGS. Comprehensive tissue and liquid-based NGS have revealed targeted treatment options for a significant number of patients. Overall Survival of patients treated with tailored therapy subsequent to NGS analysis was positively impacted in comparison to patients without an actionable target, only exceeded by patients who received targeted treatment subsequent to upfront standard molecular tests.
Clinical trial identification:
Legal entity responsible for the study:
Soroka Cancer Center, Ben-Gurion University, Beer Sheva, Israel.
Funding:
Has not received any funding
Disclosure:
S. Geva: Travel grant from Teva Pharmaceuticals, Honorarium from Guardant Health. L.C. Roisman: Lectures fees: Roche, MSD, Pfizer, Astrazenca. M. Ilouze: Honorarium from Pfizer, MSD, Roche and Takeda. A. Zer: Personal fees from Roche, grants and personal fees from BMS, personal fees from AstraZeneca, personal fees from BI, outside the submitted work. N. Peled: Advisor & Honorarium from AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Eli Lilly, FoundationMedicine, Gaurdant360, MSD, Novartis, NovellusDx, pfizer, Roche, Takeda. All other authors have declared no conflicts of interest.
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146P - The clinical impact of comprehensive cfDNA genomic testing in lung cancer (ID 566)
12:30 - 13:00 | Author(s): N. Peled
- Abstract
Background:
Next-generation sequencing (NGS) of cell-free circulating tumor DNA (cfDNA) enables a non-invasive option for comprehensive genomic analysis of lung cancer patients. Currently there is insufficient data in regard to the impact of cfDNA analysis on clinical decision making. In this study, we evaluated the clinical utility of cfDNA sequencing on treatment strategy and progression-free survival in non-small cell lung cancer (NSCLC) patients.
Methods:
In this retrospective study, data was collected from files of 116 NSCLC patients monitored between the years 2014–2017 in Israel. Plasma samples from stage IIIb/IV NSCLC patients were analyzed by a commercial test (Guardant 360), using hybrid capture, single molecule barcoding and massively parallel paired-end synthesis to sequence a targeted gene panel. This test allows the detection of somatic alterations such as point mutations, indels, fusions and copy number amplifications.
Results:
116 consecutive NSCLC patients were included in this study. Median age at diagnosis was 63 years, male:female ratio was 1:1.7. 40% (47/116) were never-smokers, 83% (96/116) had adenocarcinoma. 41.4% (48/116) were tested before 1[st] line therapy (Group A), 34.5% (40/116) upon progression on chemotherapy or immunotherapy (Group B1) and 24.1% (28/116) upon progression on EGFR TKIs (Group B2). The most common genes were EGFR sensitizing mutations (25.9%, 30/116), MET amplifications and/or exon 14 skipping mutations or resistance point mutation (9.5%, 11/116) and EGFR T790M mutations (6.9%, 8/116). Clinical outcome of cfDNA analysis and targeted therapy for the entire cohort and for each group are summarized in the Table.Table: (Abstract 146P)Clinical Outcome of cfDNA Analysis and Targeted TherapyTotal (n = 116) Group A (n = 48) Group B1 (n = 40) Group B2 (n = 28) Drug-associated actionable Mutations (On/Off Lable) 65% (75/116) 65% (31/48) 52.5% (21/40) 82% (23/28) Lung Cancer Related Actionable Mutations (NCCN guidelines) 41% (48/116) 31% (15/48) 32.5% (13/40) 71% (20/28) Tretmanet change (Impact on Decision) 26% (30/116) 23% (11/48) 25% (10/40) 32% (9/28) Response Evaluable 93% (28/30) 82% (9/11) 100% (10/10) 100% (9/9) Response not Evaluable 7% (2/30) 18% (2/11) Early cessation of treatment d/t toxicity 0% (0/10) 0% (0/9) Response Assessment (RECIST): CR 4% (1/28) 0% (0/9) 0% (0/10) 11% (1/9) Response Assessment (RECIST): PR 39% (11/28) 44% (4/9) 30% (3/10) 44% (4/9) Response Assessment (RECIST): SD 32% (9/28) 56% (5/9) 20% (2/10) 22% (2/9) Response Assessment (RECIST): PD 25% (7/28) 0% (0/9) 50% (5/10) 22% (2/9) Objective Response Rate 43% (12/28) 44% (4/9) 30% (3/10) 55.5% (5/9) Disease Control Rate 75% (21/28) 100% (9/9) 50% (5/10) 78% (7/9) Median Duration of Treatment 5 months (6/28 ongoing) 9 months (4/9 ongoing) 3.5 months (0/10 ongoing) 4 months (2/9 ongoing) Durable Disease Control Rate (over 4 months) 43% (13/30) 64% (7/11) 20% (2/10) 44% (4/9) Median PFS 3.6 months 7.3 months 2.5 months 3.3 months
Conclusions:
This study extends the evidence for clinical utility of comprehensive NGS testing by demonstrating durability of response to plasma-detected genomic alterations. cfDNA NGS changes treatment decisions in a significant number of patients in this retrospective study. It also has the potential to reduce undergenotyping of advanced NSCLC patients, while reducing costs and complications of biopsies, and facilitating more precise use of targeted therapy as well as immunotherapy.
Clinical trial identification:
Legal entity responsible for the study:
Soroka Cancer Center, Ben-Gurion University, Beer Sheva, Israel.
Funding:
Has not received any funding
Disclosure:
S. Geva: Travel grant from Teva Pharmaceuticals, Honorarium from Guardant Health. A. Dvir, L. Soussan-Gutman: Employee of Oncotest (subsidiary of Teva pharmaceuticals), the distributor of Guardant360 in Israel. L.C. Roisman: Lectures fees: Roche, MSD, Pfizer, Astrazenca. A. Zer: Personal fees from Roche, grants and personal fees from BMS, personal fees from AstraZeneca, personal fees from BI, outside the submitted work. N. Peled: Advisor & Honorarium from AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Eli Lilly, FoundationMedicine, Gaurdant360, MSD, Novartis, NovellusDx, pfizer, Roche, Takeda. All other authors have declared no conflicts of interest.
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42P - Is there a delay in diagnosis of lung cancer in women? (ID 442)
12:30 - 13:00 | Author(s): N. Peled
- Abstract
Background:
Lung cancer remains a major cause of death in the world, and while it was considered in the past to be primarily a male disease, the number of female patients has risen in recent years, such that rates among women are similar to those among men. Nevertheless, it has been found previously (in cardiovascular disease) that when there is a sex specific stereotype to a disease, it may remain entrenched in medical diagnostic processes, so as to cause belated diagnosis among the other sex. Here we aim to characterize the effects of sex on lung cancer diagnosis.
Methods:
We performed a retrospective analysis using two cohorts, 458,132 patients from the USA using the SEER (Statistics, Epidemiology and End Results) database, and 30330 patients from Israel. Patient cohorts were analyzed for sex-based differences by tumor type and stage at diagnosis, and results were stratified by race and analyzed with data regarding possible confounders such as smoking and socio-economic factors.
Results:
Male patients were more likely than female patients to be diagnosed at stage 3–4, consistent across lung cancer types, cancer registries, smoking, and racial and socioeconomic backgrounds. The exception to this was the arab population in the Israeli cohort, where there was no significant difference between men and women in the percentage diagnosed in later stages. The difference between the percentage of men vs. women diagnosed in stages 3–4 correlated negatively with increased female ever smokers and with squamous and small cell carcinoma, and were not correlated with the rate of cancer in women, or the difference between male and female cancer rates. Race was shown to have a significant effect on the percentage of women diagnosed in later stages.
Conclusions:
Results do not show a general belated diagnosis of lung cancer in women. In fact, the opposite appears to be the case. Results appear to point to the fact that smoking women are more likely to be diagnosed at later stages, which is consistent with current literature. Israeli arab women may suffer from belated lung cancer diagnosis, despite very low levels of smoking, perhaps owing to social and cultural causes.
Clinical trial identification:
Legal entity responsible for the study:
Institute of Oncology, Soroka Medical Center & Ben-Gurion University
Funding:
Has not received any funding
Disclosure:
N. Peled: Advisor & honorarium from AZ, BI, BMS, Lilly, MSD, Novartis, Pfizer, Roche, Takeda, FMI. All other authors have declared no conflicts of interest.
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67P - The influence of circulating tumor DNA analysis on response to immunotherapy in non-small cell lung cancer (NSCLC) (ID 603)
12:30 - 13:00 | Author(s): N. Peled
- Abstract
Background:
International guidelines have advocated molecular profiling as part of the standard diagnostic evaluation for advanced NSCLC, with the goal of identifying driver mutations for which effective therapies or clinical trials are available. In advanced NSCLC, immunotherapy demonstrated good response rates with some responses being remarkably durable. Understanding the molecular determinants of response to immunotherapies is a key challenge in oncology. Notably, tumor mutational burden detected by tissue next generation sequencing (NGS) was found to be correlated with response to immune checkpoint inhibitors.
Methods:
In this retrospective study, data were collected on NSCLC patients treated in multiple medical centers in Israel between 2014 and 2017. We used NGS on cell-free circulating tumor DNA (ctDNA) to evaluate whether mutational burden influences the response to immunotherapy in these patients.
Results:
Overall, 336 NSCLC patients underwent NGS on ctDNA. Of these 336 patients, 192 (57%) were females and 144 (43%) were males. The average age (range) was 64 (23–103) years. Clinical treatment information is currently available for 117 patients, of whom 50 (43%) received immune check-point inhibitors. Rates of stable disease, partial and complete responses (RECIST criteria), as well as progression-free survival and overall survival will be reported. In addition, to unravel the genomic determinants of response to immunotherapy we will use the blood-derived ctDNA to understand if hypermutated ctDNA is a predictive biomarker of response to immunotherapy.
Conclusions:
ctDNA collection was feasible in 336 patients. Prediction model to associate the ctDNA signature with response to immunotherapy will be presented.
Clinical trial identification:
Legal entity responsible for the study:
Soroka Medical Hospital
Funding:
Has not received any funding
Disclosure:
L.C. Roisman: Lectures fees from Roche, Astrazenca, MSD, Pfizer. S. Geva: Travel grant from Teva Pharmaceuticals, honorarium from Guardant Health. L. Soussan-Gutman, A. Dvir, R. Yair, T. Twito: Works at Oncotest-Teva, which is a distributor of Guardant Health in Israel. R. Larman: Employee by Guardant Health inc. N. Peled: Advisor & honorarium from AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Eli Lilly, FoundationMedicine, Gaurdant360, MSD, Novartis, NovellusDx, Pfizer, Roche, Takeda. All other authors have declared no conflicts of interest.
