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Heather A Wakelee

Moderator of

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    MA03 - Clinomics and Genomics (ID 119)

    • Event: WCLC 2019
    • Type: Mini Oral Session
    • Track: Advanced NSCLC
    • Presentations: 12
    • Now Available
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      MA03.01 - The Impact of Early Steroids on Clinical Outcomes in Patients with Advanced NSCLC Treated with Immune Checkpoint Inhibitors- A Cancerlinq Cohort (Now Available) (ID 2807)

      10:30 - 12:00  |  Presenting Author(s): Nathan Pennell  |  Author(s): Pradnya Dinkar Patil, Xuefei Jia, Brian Hobbs

      • Abstract
      • Presentation
      • Slides

      Background

      Immune checkpoint inhibitors (ICIs) have changed the treatment paradigm for patients with NSCLC, however only a fraction of patients have objective responses to these agents. Identifying clinical factors that influence efficacy of ICIs is crucial for optimal patient selection for treatment. Since ICIs produce anti-tumor responses by reinvigorating cytotoxic effector T cells, one can surmise that patients who receive steroids within a short interval of initiating ICIs will have less robust anti-tumor responses. Clinical trials usually exclude patients receiving steroids for this reason. In clinical practice, patients with NSCLC often receive corticosteroids for various indications such as brain metastases, appetite stimulation, autoimmune disorders, or COPD. By analyzing data obtained from a large real world cohort of patients with NSCLC, we aim to study the impact of early steroids (within 30 days) on clinical outcomes in patients with advanced NSCLC treated with ICIs.

      Method

      Using the Cancerlinq Discovery Database which consists of data aggregated from the electronic medical records of oncology practices, 11,143 patients with advanced NSCLC treated with ICIs were identified. Of these, 1581 patients were prescribed or administered ≥ 10 mg of prednisone or equivalent corticosteroid dose within the first 30 days of initiating ICIs. To account for prognostic heterogeneity within the population, we created matched cohorts of patients that exhibited similar prognostic clinical characteristics such as age (using 65 years as a cutoff) and gender. Association between time on treatment with ICIs and early steroid use was evaluated using the Student’s t-test. Overall survival (OS) was estimated using the Kaplan-Meier method and analyzed using the Cox proportional-hazards model.

      Result

      The cohort consisted of a predominantly white population (53.4%), with a median age of 76 years and a slight male predominance (54.9%). The median time on ICI treatment was 3.8 months. Patients who received steroids within the first 30 days had a shorter time on treatment- median of 3.36 months vs 3.86 months for those without steroid use (p= 0.023). Early steroid use was also associated with significantly worse overall survival [HR 1.16, 95% CI (1.05, 1.28) p<0.002].

      Figure: Kaplan-Meier survival analyses of patients with NSCLC treated with ICIs according to early steroid use

      p1.png

      Conclusion

      The use of ≥ 10 mg of prednisone equivalent corticosteroid dose within 30 days of initiating ICIs was associated with shorter time on treatment and worse overall survival in this large real world cohort of NSCLC patients. It is prudent that clinicians judiciously prescribe corticosteroids upon initiation of ICIs.

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      MA03.02 - Genetic Variants in ERAP1 and NCF2 in the MHC Class I Related Genes Are Associated with Non-Small Cell Lung Cancer Survival (Now Available) (ID 1491)

      10:30 - 12:00  |  Presenting Author(s): Sen Yang  |  Author(s): Qingyi Wei, David C Christiani, Qiming Wang

      • Abstract
      • Presentation
      • Slides

      Background

      Adaptive immunity, particularly the presence of tumor-infiltrating CD8+ T cells, is crucial in the control of tumor cells and preventing overall cancer progression. However, the process of CD8+ T cells recognizing and killing tumor cells depends on the expression of MHC class I (MHCI) complex presented on tumor cell surface.

      Method

      In the present study, we performed a two-phase analysis of two independently published genome-wide association studies (GWASs) to evaluate associations between genetic variants in the MHCI-related gene-set and overall survival (OS) of patients with non-small cell lung cancer (NSCLC). In the discovery GWAS dataset, we performed multivariate Cox proportional hazards regression with Bayesian false-discovery probability for multiple test corrections and evaluated associations between 9,718 single-nucleotide polymorphisms (SNPs) in 102 genes and survival of 1,185 NSCLC patients. After validation in another GWAS dataset, we performed linkage disequilibrium, function prediction and a multivariate stepwise Cox proportional hazards regression analysis.

      Result

      We found that two independent, potentially functional SNPs in two genes (ERAP1 rs469783 T>C and NCF2 rs10911362 C>T) were significantly associated with NSCLC survival, and their meta‐analysis showed an adjusted hazards ratio (HR) of 0.83 [95% confidence interval (CI) =0.77–0.89] and P meta =  8.2×10-7; 1.31 (1.06-1.73) and P meta = 0.0009; respectively. A genetic score of unfavorable genotypes of these two SNPs revealed a decreased OS in a dose–response manner (P trend < 0.0001). Further expression quantitative trait loci (eQTL) analysis showed significant associations between the genotypes and mRNA expression levels. Furthermore, the expression levels of these genes in tumor and normal tissues were different and had an effect on patient survival as well.pdf转图片- 老版.jpgpdf转图片- 老版11.jpg

      Conclusion

      Taken together, the genetic variant of the ERAP1 rs469783 and NCF2 rs10911362 from the MHCI pathway genes may be a promising predictor of survival in NSCLC patients via ERAP1 and NCF2 expression alteration.

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      MA03.03 - CEA and CYFRA 21-1 as Prognostic Biomarkers of Benefit from Nivolumab and as a Tool in Treatment Monitoring in Advanced NSCLC (Now Available) (ID 1370)

      10:30 - 12:00  |  Presenting Author(s): Filippo Gustavo Dall'Olio  |  Author(s): Francesca Abbati, Francesco Facchinetti, Francesco Gelsomino, Barbara Melotti, Maria Massucci, Sebastiano Buti, Michele Veneziani, marcello Tiseo, Andrea Ardizzoni

      • Abstract
      • Presentation
      • Slides

      Background

      To assess the role of pre-therapy levels of Carcinoembryonic antigen (CEA) and Cytokeratin-19 Fragments (CYFRA 21-1) as prognostic marker in advanced NSCLC patients treated with nivolumab, and their change as an early predictor of treatment outcome.

      Method

      This is a retrospective cohort study including all patients with stage IIIB – IV NSCLC who received nivolumab after first-line chemotherapy in 2 Italian institutions. Median Overall Survival (OS), Overall Response Rate (ORR), Disease Control Rate (DCR) and Time to Treatment Failure (TTF) were chosen as endpoints.

      Result

      100 patients were included. Cyfra 21-1 > ULN resulted correlated with OS (FIG.1A) both in univariate (HR 2.77, 95% CI 1.53 – 5.30, p 0.001) and multivariate analysis (HR 2.72, 95% CI 1.44 – 5.16, p 0.002). The only other factor correlated with OS in multivariate was ECOG PS (0-1 vs 2) (HR 5.46, 95% CI 3.07 – 9.91, p< 0.001) (Table 1).

      ECOG PS (0-1 vs 2) and CYFRA 21-1 (≤ 3.5 vs > 3.5) where combined to create a prognostic score (FIG.1B). Median OS was 23.9 months for patients without risk factors, 6.3 months with one (HR 2.75, 95% CI 1.40 – 5.40 p 0.003) and 1.3 months with 2 risk factors (HR 14.50, 95% CI 6.35 – 33.09, p< 0.001).

      Early 20% reduction after 3rd cycle was correlated with OS for CEA, HR 0.05 (95% CI 0.01–0.41), p 0,003 and borderline for CYFRA 21-1, HR 0.29 (95% CI 0.09 – 1.01), p 0.052. (FIG.1C-1D)imm per abstr.jpg.

      Univariate

      Multivariate

      Covariate

      HR (95% CI)

      P value

      HR (95%CI)

      P value

      ECOG PS 2 vs 0-1

      5.40 (3.21 – 9.09)

      < 0.001

      5.46 (3.07 – 9.91)

      < 0.001

      Cyfra > vs ≤ ULN

      2.77 (1.53 – 5.03)

      0.001

      2.72 (1.44 – 5.16)

      0.002

      Liver metastasis yes vs no

      2.19 (1.26 – 3.78)

      0.005

      0.102

      Neutrophil/lymphocyte ratio ≥ 4 vs < 4

      1.99 (1.23 – 3.20)

      0.005

      0.105

      KRAS mutated vs wild type*

      0.39 (0.21 – 0.74 )

      0.004

      0.262

      Bone metastasis yes vs no

      1.75 (1.10 – 2.79)

      0.018

      0.362

      Response to previous therapy yes vs no

      0.51 (0.29 – 0.91)

      0.023

      0.376

      CEA > vs ≤ ULN

      1.41 (0.88 – 2-25)

      0.150

      0.418

      Stage IV vs IIIB

      1.63 (0.75 – 3.54)

      0.22

      0.449

      Squamous vs non squamous

      0.79 (0.48 – 1.28)

      0.334

      0.689

      Smoker vs never smoker

      0.88 (0.65 – 1.18)

      0.386

      0.694

      Second-line vs third or more

      0.94 (0.60 – 1.47)

      0.77

      0.843

      Brain metastasis yes vs no

      1.16 (0.66 – 2.04)

      0.603

      0.594

      Conclusion

      Our data suggests that Cyfra 21-1 pre-therapy assessment, both alone and in combination with other factors in a prognostic/predictive score, may provide clinicians with further information on the prognosis of patients treated with nivolumab.

      CEA and CYFRA 21-1 repeated measures could be useful as an early surrogate marker of clinical benefit.

      Further analysis are warranted to confirm these findings.

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      MA03.04 - Discussant - MA03.01, MA03.02, MA03.03 (Now Available) (ID 3723)

      10:30 - 12:00  |  Presenting Author(s): Nathan Pennell

      • Abstract
      • Presentation
      • Slides

      Abstract not provided

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      MA03.05 - BRAF Mutations Are Associated with Increased Benefit from PD1/PDL1 Blockade Compared with Other Oncogenic Drivers in Non-Small Cell Lung Cancer (Now Available) (ID 1472)

      10:30 - 12:00  |  Presenting Author(s): Marcelo Vailati Negrao  |  Author(s): Ferdinandos Skoulidis, Meagan Montesion, Katja Schulze, Ilze Bara, Vincent Shen, Sylvia Hu, Yasir Elamin, Xiuning Le, Michael E Goldberg, Chang-Jiun Wu, Jianhua Zhang, David S Barreto, Waree Rinsurongkawong, George R Simon, Jack Roth, Stephen Swisher, Jack Lee, Anne Tsao, Vassiliki A Papadimitrakopoulou, Don Lynn Gibbons, Bonnie Glisson, Vincent A Miller, Brian Alexander, Garrett M Frampton, Lee A Albacker, David S Shames, Jianjun Zhang, John Victor Heymach

      • Abstract
      • Presentation
      • Slides

      Background

      PD-1/PD-L1 immune checkpoint blockade (ICB) has revolutionized the treatment of non-small cell lung cancer (NSCLC), but only a minority of patients achieve durable clinical benefit. Although classic EGFR/ALK alterations are correlated with ICB resistance, it is unknown if patients with other molecular subtypes of NSCLC also derive poorer outcomes from ICB. We investigated if there are oncogene-driven NSCLC associated with higher response rates (RR) and progression-free survival (PFS) to ICB.

      Method

      Two independent retrospective cohorts of oncogene-driven NSCLC treated with ICB monotherapy were analyzed for clinical outcome: MD Anderson (MDACC) and Flatiron Health-Foundation Medicine Clinico-Genomic Database (FH-CGDB). PD-L1 expression (Dako 22C3 - FoundationCore) and tumor mutational burden (TMB - FoundationCore; TCGA and MSK-IMPACT – cbioportal.org) were compared across distinct molecular subtypes of NSCLC to determine differences in clinical outcome.

      Result

      Among five oncogene defined groups from the MDACC cohort, BRAF-mutant NSCLC had the highest response rate (RR) (RECIST 1.1) (P<0.01) and PFS (P<0.01) when treated with ICB (Table). These differences remained significant after adjusting for PD-L1 expression. Classic EGFR and HER-2 mutant NSCLC had the lowest RR and PFS (Table). Similar results were observed in the independent FH-CGDB cohort where BRAF-mutant NSCLC had longer real-world (rw) PFS and OS to ICB monotherapy (Table). PD-L1 expression (tumor score ≥1% and ≥50%) and TMB were higher in BRAF-mutant NSCLC compared to EGFR and HER-2 (P<0.01). BRAF V600E NSCLC had lower TMB compared to non-V600E (5.9 vs 13.7 mut/Mb, P<0.01), but both had high PD-L1 expression (≥1%: 72% vs 61%; ≥50%: 42% vs 32%).

      KRAS

      BRAF

      Classic EGFR

      EGFR exon 20

      HER2

      MDACC cohort

      Patients – N

      87

      10 (V600E 3 / non-V600E 7)

      28

      25

      15

      RR – %

      24.3

      62.5

      4.5b

      10b

      8.3

      Median PFS – mo (95% CI)

      2.76

      (2.23-3.30)

      7.37 (not estimable)a

      1.78 (1.18-2.37)

      2.73 (1.71-3.75)

      1.88 (1.63-2.12)

      FH-CGDB

      Patients – N

      503

      68 (V600E 32 / non-V600E 36)

      52

      42

      25

      Median rwPFS -

      mo (95% CI)

      3.55

      (3.15-4.24)

      6.0

      (2.89-11.6)

      2.17b

      (1.77-2.63)

      2.66b

      (2.23-5.13)

      1.87b (1.31-4.34)

      Median rwOS – mo (95% CI)

      10.28

      (8.51-12.02)

      16.07

      (8.64-NA)

      5.29b

      (3.25-17.68)

      9.89b

      (3.68-20.86)

      10.81

      (4.17-NA)

      FoundationCore cohort – N

      NA

      188 (V600E 74 / non-V600E 114)

      386

      96

      57

      TMB – mean (mut/Mb)

      NA

      10.6a

      3.7

      3.8

      5.8

      PD-L1 TPS ≥ 50% (%)

      NA

      36a

      19

      23

      16

      a: P<0.01 vs all groups; b: P<0.05 for pairwise comparison vs BRAF.

      Conclusion

      NSCLCs with BRAF mutations are associated with increased benefit from ICB when compared to tumors harboring other targetable oncogenic drivers. Oncogene driver mutations are associated with distinct patterns of TMB and PD-L1 expression. These findings highlight the importance of developing mutation-specific clinical trials in NSCLC.

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      MA03.06 - Efficacy Results of Selective AXL Inhibitor Bemcentinib with Pembrolizumab Following Chemotherapy in Patients with NSCLC (Now Available) (ID 2271)

      10:30 - 12:00  |  Presenting Author(s): Enriqueta Felip  |  Author(s): Paal Brunsvig, Åslaug Helland, Nuria Viñolas, Santiago Ponce Aix, Enric Carcereny, Manuel Dómine, Jose Manuel Trigo Perez, Edurne Arriola, Rosario Garcia Campelo, James Spicer, Jonathan Robert Thompson, Ana Laura Ortega Granados, Robert J. Holt, Dominic Smethurst, James B. Lorens, Muhammad Shoaib, Abdul Siddiqui, Julia Schoelermann, Katherine Lorens, Emmett V. Schmidt, Michael Jon Chisamore, Matthew Krebs

      • Abstract
      • Presentation
      • Slides

      Background

      The RTK AXL is implicated in epithelial-to-mesenchymal transition, negative regulation of anti-tumour immunity and resistance to multiple therapies including immune checkpoint inhibitors.

      Bemcentinib (BGB324) is a first-in-class, oral, highly selective and potent AXL inhibitor which has been demonstrated to enhance anti-PD1 therapy.

      Method

      This phase II trial (Cohort A, NCT03184571) enrolled 48 advanced lung adenocarcinoma patients with progression on or after no more than one prior line of platinum-based chemotherapy. Patients with EGFR/ALK mutations were included in this study and must have progressed on or after at least one standard targeted therapy. The primary endpoint was ORR according to RECIST v1.1. Additional endpoints included efficacy according to biomarker expression, DCR, PFS, OS, and safety. Tumour biopsies were analysed for PD-L1 expression (22C3 pharmDx), AXL by IHC, and infiltrating immune cells.

      Result

      As of April 2019, the trial was fully recruited: median age 65 (range 39-82) yrs, 61% male, 76% smokers or ex-smokers.

      At time of writing, a total of 210 treatment cycles had been completed by all patients. 17 patients were ongoing.

      17 of 32 biomarker-evaluable patients (53%) were PD-L1 negative, 13 (41%) had TPS 1-49%, and 2 (6%) had TPS >50%. Of 28 biomarker-evaluable patients, 14 (50%) expressed AXL on their tumours.

      Among patients who had at least 1 evaluable on-treatment scan: 5 responses were observed in 13 AXL positive patients (38%), and 7 in 30 patients with TPS 0-49% (23%). There were 10 responses observed among 34 evaluable patients overall (29%).

      In Stage 1, two of the 4 AXL positive responses are ongoing; mDoR is not mature in the AXL positive patients. mPFS was 5.9 mo in AXL positive patients (n=10, 3.0-NR) and 4.0 mo (95% CI 1.9-NR) overall (n=24). mOS was not mature.

      The most common TRAEs (occurring in >10% of patient in both stages) were transaminase increases (34%), asthenia/fatigue (30%), diarrhoea (26%), nausea (13%), anaemia (11%), decreased appetite (11%), and pruritus (11%). All cases of transaminase increase were reversible and resolved with concomitant administration of systemic corticosteroids and interruption of study treatments.

      Conclusion

      Patients had predominantly low or no PD-L1 expression; approximately half were AXL positive. The combination of bemcentinib and pembrolizumab was well tolerated and showed promising efficacy in previously treated IO-naïve NSCLC patients, particularly in those with AXL positive disease, including PD-L1 negative patients. Mature ORR for both stages, as well as 12-month OS for stage 1 will be presented at the meeting.

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      MA03.07 - First-Line Atezolizumab Chemoimmunotherapy in Advanced Non-Squamous NSCLC Patients Harboring EGFR/ALK Genetic Alterations (Now Available) (ID 1163)

      10:30 - 12:00  |  Presenting Author(s): Kyaw Zin Thein  |  Author(s): Nusrat Jahan, Aung Myint Tun, Anita Sultan, Sriman Swarup, Francis Mogollon-Duffo, Rachana Yendala, Miguel Quirch, Thura Win Htut, Nicholas D’cunha, Shabnam Rehman, Fred Hardwicke, Sanjay Awasthi, Lukman Tijani

      • Abstract
      • Presentation
      • Slides

      Background

      Management of advanced non-squamous non-small cell lung cancer (NSCLC) is an area in dire need of therapeutic innovation. In recent years, multiple randomized clinical trials (RCT) have combined atezolizumab, programmed death ligand 1 (PDL-1) antibody, with chemotherapy as first-line treatment of advanced non-squamous NSCLC. In patients with EGFR/ ALK genetic alterations, PDL-1 or programmed death receptor 1 (PD-1) inhibitors monotherapy previously failed to demonstrate survival benefits compared to standard chemotherapy. The purpose of our study is to explore the efficacy of atezolizumab in combination with chemotherapy for first-line treatment of advanced non-squamous NSCLC harboring EGFR or ALK genetic alterations.

      Method

      We conducted a comprehensive literature search using PUBMED, MEDLINE, EMBASE databases and meeting abstracts from inception through March 2019. RCTs utilizing first-line atezolizumab combination regimen in patients with advanced non-squamous NSCLC were incorporated in the analysis. A generic inverse variance method was used to calculate the estimated pooled hazard ratio (HR) for progression-free survival (PFS) with 95% confidence interval (CI). Heterogeneity was assessed with Cochran's Q -statistic. Random effects model was applied.

      Result

      3 RCTs (IMpower – 130, 132 and 150) including 2101 patients with advanced non-squamous NSCLC were eligible. The study arm used standard chemotherapy regimens in combination with atezolizumab while control arm used only standard chemotherapy regimens. The randomization ratio was 2:1 in IMpower130 study and 2:1 in other studies. The I2statistic for heterogeneity was 0, suggesting homogeneity among RCTs. 1949 patients were EGFR/ ALK wild type and 152 patients from Impower 130 and 150 were positive for EGFR/ ALK genetic alterations. The pooled HR for PFS was statistically significant at 0.62 (95% CI: 0.56- 0.69; P < 0.0001) in patients with EGFR or ALK genetic alterations, favoring first-line atezolizumab chemoimmunotherapy regimen. In the EGFR/ ALK wild type population, the pooled HR for PFS was 0.63 (95% CI: 0.43 to 0.94; P = 0.02).

      Conclusion

      Our meta-analysis demonstrated that atezolizumab in combination with chemotherapy significantly improved progression-free survival compared to standard chemotherapy in patients with advanced non-squamous NSCLC, regardless of the presence or absence of EGFR/ ALK genetic alterations.

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      MA03.08 - Discussant - MA03.05. MA03.06, MA03.07 (Now Available) (ID 3724)

      10:30 - 12:00  |  Presenting Author(s): Myung-Ju Ahn

      • Abstract
      • Presentation
      • Slides

      Abstract not provided

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      MA03.09 - Dramatic Responses to Immune Checkpoint Inhibitors in MET Exon 14 Skipping Mutation (METex14mut) Non Small Cell Lung Cancers (Now Available) (ID 1621)

      10:30 - 12:00  |  Presenting Author(s): Marie Mayenga  |  Author(s): Isabelle Monnet, Marie-Ange Massiani, Jean-Baptiste Assié, Laure Tabeze, Sylvie Friard, Severine Fraboulet, Anne-Cécile Metivier, Christos Chouaid, Leila Zemoura, Elisabeth Longchampt, Samia Melaabi, Louis-Jean Couderc, Helene Doubre

      • Abstract
      • Presentation
      • Slides

      Background

      METex14 mutations occur in 2-3% of Non-Small-Cell Lung Cancers (NSCLC), with a higher prevalence in patients aged over 70-years-old, non-smokers.and women. Crizotinib, a MET-inhibitor, allows remarkable, but often short, tumor responses. Immune Checkpoint Inhibitors (ICIs) have become pivotal treatments in NSCLC but seem less efficient in non-smokers and in case of oncogenic addiction. We report durable strong responses in four non-smoker women (A, B, C, D) and two smokers (E, F) treated by ICIs in a second-line setting for NSCLC harboring METex14 mut.

      Method

      We studied the clinical and biological characteristics and the tumor response after ICIs for each patient. The complete DNA sequencing of the tumor was available after the beginning of ICIs (explaining why crizotinib was not proposed in second line). PDL1 expression on tumor cells was evaluated by antibody clone E1L3N (Cell signaling Technology).

      Result

      Table 1 summarizes patient and tumor characteristics, and the evolution during ICIs : Nivolumab for all patients except E (pembrolizumab). There were neither EGFR, BRAF, KRAS mutations, nor ALK or ROS translocations (except minority KRAS mutation for C). No concurrent MET amplification was found.

      tableau.jpeg

      Partial or complete response was rapidly (2 months) obtained in five patients, while pseudo-progression was first observed in D. After a grade 3 diarrhea and diabetic ketoacidosis, ICI was stopped in A but the reintroduction one year later did not cause any toxicity. The tolerance was excellent for the 5 other patients. Response was maintained from 16 to 40 months and treatment is ongoing in four patients. C stopped ICI after 26 months (Complete response on PETscan). B had an isolated bone progression after 7 months of ICI which benefited from a local radiotherapy. After almost 2 years of ICI, a multisite progression occurred and crizotinib was proposed.

      Conclusion

      ICIs should be discussed in the treatment of METex14 mut NSCLC.

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      MA03.10 - Prospective Evaluation of a Prognostic Clinico-Molecular Score (DEMo) to Predict Outcome of Advanced NSCLC Patients Treated with Immunotherapy (Now Available) (ID 1378)

      10:30 - 12:00  |  Presenting Author(s): Arsela Prelaj  |  Author(s): Claudia Proto, Giuseppe Lo Russo, Diego Signorelli, Roberto Ferrara, Mavis Mensah, Giulia Galli, Alessandro De Toma, Giovanni Randon, Filippo Pagani, MARTA Brambilla, Benedetta Trevisan, Monica Ganzinelli, Nicoletta Zilembo, Filippo Guglielmo Maria De Braud, VALTER Torri, Marina Chiara Garassino, Gabriella Sozzi, Mattia Boeri

      • Abstract
      • Presentation
      • Slides

      Background

      We have already reported three different molecular (MSC: plasma miRNA-signature classifier, Boeri, Clin Cancer Res 2019) and clinico-biochemical scores (DiMaio: Di Maio, EJC 2010; EPSILoN: Ann.Onco 2018 supp) able to differently predict prognosis in advanced non-small cell lung cancer (aNSCLC) patients treated with immunotherapy (IO). Exploiting the ability of each test we developed a combined clinico-biological composite score called DEMo (DiMaio EPSILoN MSC). Objective of the study is to prospectively evaluate the prognostic value of DEMo in aNSCLC patients treated with IO.

      Method

      We enrolled 127 consecutive aNSCLC patients treated with IO in first (n=37) and further-lines (n=90) at Istituto Nazionale dei Tumori, Milan. All patients had complete clinico-laboratoristic data necessary for both scores: DiMaio (ECOG-PS, sex, histology, stage, uses of platinum-based therapy at first-line and response to first-line) and EPSILoN (ECOG-PS, Smoke, Liver, LDH, NLRatio). MSC was prospectively evaluated in plasma samples collected prior starting IO and the risk level were assessed. Progression-free survival (PFS) and overall survival (OS) in strata of MSC/DiMaio/EPSILoN alone or DEMo and overall response rate (ORR), were considered as endpoints. Kaplan Meier were used to generate survival curves and Cox hazard model were employed to perform multivariate analyses.

      Result

      In multivariate analyses, adjusted for age, sex, pack/year and ECOG-PS, patients with high MSC and high DiMaio and EPSILoN scores reported a lower PFS (MSC: HR 1.72 CI95% 1.06 – 2.77, p=0.027; DiMaio: HR 2.63 CI95% 1.40 – 5.00, p=0.002; EPSILoN: HR 2.17 CI95% 1.16 – 4.16, p=0.014) and OS (MSC: HR 2.17 CI95% 1.29 – 3.70, p=0.003; DiMaio: HR 3.57 CI95% 1.66 – 7.69, p=0.001; EPSILoN: HR 2.50 CI95% 1.15 – 5.26, p=0.020). DEMo stratified patients into four risk groups according to the presence of 3–2–1–0 bad markers (High MSC/DiMaio/EPSILoN or none). Groups had 0%–0%–32.2%–53.3% 1-year PFS (p<0.0001) and 4.4%– 19.4% – 66.9% – 75.4% 1-year OS (p<0.0001). We further compared 0/1 to 2/3 combined groups. At the multivariate Cox model group 2/3 had a mPFS 1.9 vs 9.4 mo compared to group 0/1 (HR 3.70 CI95% 2.08 – 6.67, p<0.0001) and mOS 4.1 vs 22.4 mo (HR 4.76 CI95% 2.56 – 9.10, p<0.0001). Regarding ORR, DEMo group 0/1 had a 3.86 (CI95% 1.76-8.47) fold higher probability to respond compare to 2/3 group (p=0.0007).

      Conclusion

      DEMo composite biomarker is able to predict better prognosis compared to each single score and can be a useful tool for guiding IO treatment choices. In particular, DEMo allowed a good selection for those patients who are less likely to benefit from IO.

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      MA03.11 - Chemotherapy After PD-1 Inhibitors Versus Chemotherapy Alone in Patients with Non–Small Cell Lung Cancer (WJOG10217L) (Now Available) (ID 409)

      10:30 - 12:00  |  Presenting Author(s): Hirotsugu Kenmotsu  |  Author(s): Eriko Miyawaki, Ryoji Kato, Hidetoshi Hayashi, Yasutaka Chiba, Junichi Shimizu, Tomohiro Ozaki, Daichi Fujimoto, Ryo Toyozawa, Yuki Akazawa, Motoyasu Okuno, Sayako Morikawa, Tatsuo Ohira, Taishi Harada, Ryota Ushio, Akihito Kubo, Toshiyuki Harada, Nozomu Kimura, Hiroyuki Yamaguchi, Kazuo Nishikawa, Nobuyuki Yamamoto, Kazuhiko Nakagawa

      • Abstract
      • Presentation
      • Slides

      Background

      Studies have suggested that chemotherapy after immune checkpoint inhibitors may confer an improved response in patients with non–small cell lung cancer (NSCLC). However, potential selection bias in such studies has not been addressed. We therefore applied propensity score analysis to investigate the efficacy of subsequent chemotherapy after PD-1 inhibitors (CAP) compared with chemotherapy alone.

      Method

      We conducted a multicenter retrospective cohort study for patients with advanced or recurrent NSCLC who were treated at 47 institutions across Japan between 1 April 2014 and 31 July 2017 with chemotherapy (docetaxel with or without ramucirumab; S-1; or pemetrexed) either after PD-1 inhibitor therapy (CAP cohort) or alone (control cohort). The primary end point was objective response rate (ORR). Inverse probability weighting (IPW) was applied to adjust for potential confounding factors, including age, sex, smoking status, performance status, histology, EGFR or ALK genetic alterations, brain metastasis, and recurrence after curative radiotherapy.

      Result

      A total of 1439 patients (243 and 1196 in the CAP and control cohorts, respectively) was available for unadjusted analysis. Several baseline characteristics—including age, histology, EGFR or ALK alterations, and brain metastasis—differed significantly between the two cohorts. After adjustment for patient characteristics with the IPW method, ORR was 18.9% for the CAP cohort and 10.8% for the control cohort (ORR ratio, 1.75; 95% confidence interval [CI], 1.25–2.45; P = .001). Median PFS was 3.5 and 2.6 months for the CAP and control cohorts, respectively (hazard ratio [HR], 0.862; 95% CI, 0.743–0.998; P = .048). The PFS rate at 3, 6, and 12 months was 53.3%, 28.5%, and 4.6%, respectively, for the CAP cohort, and 44.3%, 19.7%, and 6.1% for the control cohort. Median OS was 9.8 months for the CAP cohort and 10.3 months for the control cohort (HR, 0.979; 95% CI, 0.813–1.179; P = .822).

      Conclusion

      After adjustment for selection bias using propensity score–weighted analysis, CAP showed a significantly higher ORR and longer PFS compared with chemotherapy alone, with the primary end point of ORR being achieved. However, these results did not translate into an OS advantage, and no PFS benefit was apparent at 12 months despite the improvement observed at 3 and 6 months. Our findings suggest that prior administration of PD-1 inhibitors may result in a synergistic antitumor effect with subsequent chemotherapy, but that such an effect is transient. CAP therefore does not appear to achieve durable tumor control or confer a lasting survival benefit.

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      MA03.12 - Discussant - MA03.09, MA03.10, MA03.11 (Now Available) (ID 3725)

      10:30 - 12:00  |  Presenting Author(s): HOWARD WEST

      • Abstract
      • Presentation
      • Slides

      Abstract not provided

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    MA06 - Challenges in the Treatment of Early Stage NSCLC (ID 124)

    • Event: WCLC 2019
    • Type: Mini Oral Session
    • Track: Treatment of Early Stage/Localized Disease
    • Presentations: 1
    • Now Available
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      MA06.07 - E1505: Adjuvant Chemotherapy +/- Bevacizumab for Early Stage NSCLC: Updated Chemotherapy Subset Analysis (Now Available) (ID 2885)

      13:30 - 15:00  |  Presenting Author(s): Heather A Wakelee

      • Abstract
      • Presentation
      • Slides

      Background

      Adjuvant chemotherapy (chemo) for resected early stage NSCLC provides modest survival benefit with limited comparison data between regimens. From this trial we previously reported that adding bevacizumab (B) to adjuvant chemo failed to improve either disease free survival (DFS) or overall survival (OS). Here we update outcomes by chemotherapy regimen with an additional 30 months of follow-up.

      Method

      Enrolled patients with resected early stage NSCLC, stratified by stage, histology, sex, and chemo option, were randomized 1:1 to chemo alone or with B (15 mg/kg every 3 weeks for up to 1 year). Chemo consisted of a planned 4 cycles of every 3 week cisplatin with either vinorelbine (V), docetaxel (D), gemcitabine (G) or pemetrexed (P).

      Result

      From July 2007 to September 2013, 1501 patients were enrolled with this distribution of chemo: V 25.0%, D 22.9%, G 18.9% and P 33.2%. P was added in 2009 and restricted to non-squamous (NSq) pts. Chemo regimen was chosen (not randomized). Arms were well balanced for known prognostic factors; 28% had Sq histology. Median f/up per chemo group is: V 83.5 months(m); D 89.9m; G 87.8m; P 71.9m. In pooled analysis DFS differed by histology ranging from 29.9m(G)-43.5m(V) for NSq and 59.4m(V)-77.3m(G) for Sq. OS also differed by histology ranging from 80m(D)-98.8m(P) for NSq and 98m(G)-119m(V) for Sq. A non-significant decline in both DFS and OS was seen when B was added to D or V regimens, regardless of histology. Conversely, the addition of B to P improved both DFS (HR 0.74, p= .00994) and OS (HR 0.65, p= .00368). We thus compared outcomes across non-B regimens and though numerical differences were seen in median DFS and OS, these failed to reach statistical significance. Toxicity details were presented previously.

      Conclusion

      B did not improve OS when added to adjuvant chemo for patients with surgically resected early stage NSCLC, though variable DFS and OS outcomes by chemotherapy regimen have emerged with longer-term follow-up. These include a significant positive improvement in DFS and OS with B combined with P and trends of worse outcomes when B was added to other regimens. Ongoing molecular analysis of samples will hopefully elucidate the etiology of these differences.

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    MA11 - Immunotherapy in Special Populations and Predictive Markers (ID 135)

    • Event: WCLC 2019
    • Type: Mini Oral Session
    • Track: Immuno-oncology
    • Presentations: 1
    • Now Available
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      MA11.11 - STK11/LKB1 Genomic Alterations Are Associated with Inferior Clinical Outcomes with Chemo-Immunotherapy in Non-Squamous NSCLC (Now Available) (ID 2898)

      14:00 - 15:30  |  Author(s): Heather A Wakelee

      • Abstract
      • Presentation
      • Slides

      Background

      Addition of pembrolizumab (P) to platinum-doublet chemotherapy [carboplatin (or cisplatin) and pemetrexed (CP)] prolongs overall survival and is a standard of care (SOC) for the 1st line treatment of metastatic EGFR/ALK wild-type (wt) non-squamous non-small cell lung cancer (mnsNSCLC). Despite widespread use of the CPP regimen, molecular determinants of clinical benefit from the addition of P to CP remain poorly defined. We previously identified genomic alterations in STK11/LKB1 as a major driver of primary resistance to PD-1/PD-L1 blockade in mnsNSCLC. Here, we present updated data on the impact of STK11/LKB1 alterations on clinical outcomes with CPP chemo-immunotherapy from a large retrospective multi-institution international study.

      Method

      620 pts with mnsNSCLC and tumor genomic profiling encompassing STK11/LKB1 from 21 academic institutions in the US and Europe were included in this study. Clinical outcomes were collected for two distinct patient cohorts: a) 468 pts treated with first-line CPP (or >1st line following FDA-approved TKIs) that were alive for 14 days thereafter and b) 152 STK11/LKB1-mt pts that received CP prior to regulatory approval of CPP.

      Result

      Among 468 CPP-treated pts, STK11/LKB1 genomic alterations (N=118) were associated with significantly shorter PFS (mPFS 5.0m vs 6.8m, HR 1.45, 95% CI 1.11 to 1.91; P=0.007) and shorter OS (mOS 10.6m vs 16.7m, HR 1.46, 95% CI 1.04 to 2.07; P=0.031) compared with STK11/LKB1-wt tumors (N=350). The likelihood of disease progression as BOR to CPP differed significantly between the two groups (29.5% vs 17%, P= 0.006). Similar results were obtained when limiting the analysis to EGFR and ALK-wt tumors (N=435) (mPFS 5.0m vs 6.9m, HR 1.48, 95% CI 1.12-1.95, P=0.006 and mOS 10.6m vs 16.7m, HR 1.45, 95% CI 1.02-2.05, P=0.036). Importantly, in pts with STK11/LKB1-mt mnsNSCLC, addition of pembrolizumab to CP did not result in significant improvement of PFS (mPFS 5.0m vs 3.9m, HR 0.82, 95% CI 0.63 to 1.07, P=0.14) or OS (mOS 10.6m vs 9.1m, HR 0.93, 95% CI 0.67 to 1.30, P=0.69) compared to CP alone.

      Conclusion

      In mnsNSCLC, STK11/LKB1 alterations define a subgroup of pts with inferior clinical outcomes with CPP and lack of benefit from the addition of pembrolizumab to CP chemotherapy. Novel therapeutic strategies are required to establish effective antitumor immunity in STK11/LKB1-mutant NSCLC.

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    MS04 - New Systemic Adjuvant/Neo-Adjuvant Strategies in Early Stage Lung Cancer: Targeted Therapy and I/O (ID 67)

    • Event: WCLC 2019
    • Type: Mini Symposium
    • Track: Treatment of Early Stage/Localized Disease
    • Presentations: 1
    • Now Available
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      MS04.03 - Adjuvant PD-(L)1 Checkpoint Inhibitors (Now Available) (ID 3457)

      15:15 - 16:45  |  Presenting Author(s): Heather A Wakelee

      • Abstract
      • Presentation
      • Slides

      Abstract

      Advances in adjuvant therapy for early stage, resectable, non-small cell lung cancer (NSCLC) have been slow for many years. Four cycles of post-operative platinum-based chemotherapy remains the standard of care in most of the world, yet this confers a survival benefit of only ~5% at 5 years.1 Early efforts to stimulate adaptive immunity to prevent tumor recurrence via several immunologic interventions including antigen specific cancer vaccines, Bacillus Calmette-Guerin (BCG), adoptive cell transfer and tumor-infiltrating lymphocytes failed to show a benefit in overall survival in a meta analysis of the early trials2,3 In 2018 though positive results from the PACIFIC trial ushered in a new era of immunotherapy with PD-L1 checkpoint blockade in non-operable, stage III non-small cell lung cancer (NSCLC) and established consolidation durvalumab following chemoradiation as the new standard of care.4 These data provided further enthusiasm for ongoing trials of checkpoint inhibitors in early stage, surgically resectable disease.

      Promising preliminary data has been presented from ongoing neoadjuvant PD-(L)1 checkpoint inhibitor trials, many of which contain an adjuvant component. The most exciting results to date have come from the NADIM trial of neoadjuvant carboplatin/paclitaxel/nivolumab followed by adjuvant nivolumab for one year after surgical resection. Analysis of the first 41 patients following surgical resection showed 35 (86%) of patients with a major pathologic response (MPR) (defined as <10% viable tumor cells present) and of those, 25 (71%) had a complete pathologic response (CR).5 The NEOSTAR study of induction nivolumab or nivolumab/ipilumumab and the LCMC trial with neoadjuvant followed by adjuvant atezolizumab in resectable NSCLC patients were both updated at ASCO 2019 with reported MPR in 17%, 33%, and 19% (with 5% CR) of the nivolumab and nivolumab/ipilumumab and atezolizumab intent to treat populations, respectively.6,7 However, immune toxicity was reported in all of these trials and there were some patients who were not able to complete definitive surgery. We also do not know how MPR with immune therapy correlates with disease free survival (DFS) and overall survival (OS).

      Thus there is still a lot of enthusiasm for the post-operative (adjuvant) use of checkpoint inhibitors. There are multiple adjuvant immunotherapy trials currently underway although there are no results reported to date. A branch of the US coopertive network (NCTN) ALCHEMIST trial, ANVIL, is currently enrolling patients with stage IB (>4cm)-IIIA NSCLC who test negative for EGFR and ALK mutations. After completion of surgical resection and standard of care adjuvant therapy (chemotherapy or radiation therapy if indicated), patients are randomized to up to a year of adjuvant nivolumab or observation. These patients are further stratified by stage, histology, adjuvant treatment received and PD-L1 status (≥1% or <1%). Co-primary endpoints are disease free and overall survival.8 IMpower 010 is a randomized, phase III trial of adjuvant atezolizumab vs supportive care in stage IB (>4cm) - IIIA NSCLC patients following surgical resection and cisplatin-based adjuvant chemotherapy with enrollment of 1280 patients. This study does not allow for radiation therapy and mandates that the adjuvant chemotherapy contain cisplatin plus vinorelbine, gemcitabine, docetaxel or pemetrexed. Following completion of 4 cycles of adjuvant chemotherapy, patients are randomized 1:1 to a year of atezolizumab or observation. Primary outcome is disease free survival.9 In KEYNOTE-091 patients with IB/II-IIIA surgically resected NSCLC who have completed standard of care adjuvant therapy will be randomized to one year of pembrolizumab vs supportive care. The target enrollment is 1080 patients. Primary endpoint is disease free survival. Finally, adjuvant durvalumab is being examined in a randomized, phase III prospective, triple-blind, placebo controlled trial of patients with stage IB (>4cm)-IIIA resected NSCLC being lead by the Canadian Cancer Trials Group. Standard adjuvant chemotherapy is permitted, but post-operative radiation is only allowed for N2 disease. Primary endpoint is disease free survival in PD-L1 positive patients and in all randomized patients. The study stratifies across PD-L1 subgroups (≤1%, 1-49% and ≥50%). Target enrollment is 1360 patients.10

      Checkpoint inhibitor therapy has been established as the new standard of care in unresectable and metastatic NSCLC. Many trials are underway with adjuvant and neoadjuvant immunotherapy for early stage lung cancer and preliminary data from the neoadjuvant trials are promising. In a setting where patients have only modestly benefited from chemotherapy, we eagerly await the results of the ongoing adjuvant immunotherapy studies with the hopes of improving outcomes for surgically resectable NSCLC.

      References

      1. Pignon JP, et al. Lung adjuvant cisplatin evaluation: a pooled analysis by the LACE Collaborative Group. J Clin Oncol. 2008;26(21):3552-3559.

      2. Somasundaram A, Burns TF. Pembrolizumab in the treatment of metastatic non-small-cell lung cancer: patient selection and perspectives. Lung Cancer (Auckl). 2017;8:1-11.

      3. Zhu J, et al. Immunotherapy (excluding checkpoint inhibitors) for stage I to III non-small cell lung cancer treated with surgery or radiotherapy with curative intent. Cochrane Database Syst Rev. 2017;12:CD011300.

      4. Antonia SJ, et al. Overall Survival with Durvalumab after Chemoradiotherapy in Stage III NSCLC. N Engl J Med. 2018.

      5. Provencio-Pulla M, , et al. Neoadjuvant chemo/immunotherapy for the treatment of stages IIIA resectable non-small cell lung cancer (NSCLC): A phase II multicenter exploratory study—NADIM study-SLCG. Journal of Clinical Oncology. 2018;36(15_suppl):8521-8521.

      6. Cascone T, et al. Neoadjuvant nivolumab (N) or nivolumab plus ipilimumab (NI) for resectable non-small cell lung cancer (NSCLC): Clinical and correlative results from the NEOSTAR study. ASCO 2019.

      7. Kwiatkowski DJ, et al. Neoadjuvant Atezolizumab in Resectable Non-Small Cell Lung Cancer (NSCLC): Interim Analysis and Biomarker Data From a Multicenter Study (LCMC3). ASCO 2019

      8. Chaft JE, et al. EA5142 adjuvant nivolumab in resected lung cancers (ANVIL). Journal of Clinical Oncology. 2018.

      9. Wakelee HA, et al. A phase III trial to compare atezolizumab (atezo) vs best supportive care (BSC) following adjuvant chemotherapy in patients (pts) with completely resected NSCLC: IMpower010. Journal of Clinical Oncology. 2017;35(15_suppl):TPS8576-TPS8576

      10. O'Brien MER, et al. EORTC-ETOP randomized, phase 3 trial with anti-PD-1 monoclonal antibody pembrolizumab versus placebo for patients with early stage non-small cell lung cancer (NSCLC) after resection and standard adjuvant chemotherapy: PEARLS (NCT02504372). Journal of Clinical Oncology. 2016;34(15_suppl):TPS8571-TPS8571.

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    OA08 - Advanced Models and "Omics" for Therapeutic Development (ID 133)

    • Event: WCLC 2019
    • Type: Oral Session
    • Track: Biology
    • Presentations: 1
    • Now Available
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      OA08.03 - A Single-Cell Resolution Map of EMT and Drug Resistance States for Evaluating NSCLC Clinical Specimens (Now Available) (ID 2771)

      11:00 - 12:30  |  Author(s): Heather A Wakelee

      • Abstract
      • Presentation
      • Slides

      Background

      The role of epithelial-mesenchymal transition (EMT) in NSCLC is well reported and has been shown to prime cells for metastasis. EMT can be adopted or reversed (i.e. mesenchymal-epithelial transition, MET) by cells, revealing plasticity that can also lead to drug resistance. Although it is appreciated that EMT is not a binary process of two extremes but instead a spectrum of intermediate states of EMT phenotypes, these are poorly defined at the single-cell proteomic level in NSCLC clinical specimens. Our overall goal was to dynamically capture and characterize EMT-related drug resistance states in lung cancer cells to construct a single-cell resolution state map of clinical applicability.

      Method

      We used mass cytometry (CyTOF) time-course experimentation and novel computational tools to analyze TGFβ and drug treated NSCLC cell lines, as well as NSCLC clinical samples to identify clinically relevant drug resistant EMT and MET states and construct a single-cell resolution proteomic map of phenotypic states.

      Result

      Through TGFβ treatment and withdrawal we resolved previously unrealized EMT and MET states in NSCLC cell lines by analyzing the expression of up to 30 surface and intracellular markers. Using a novel computational tool (TRACER) we also provide evidence that EMT and MET trajectories differ and exert differential drug sensitivity profiles. We used the identified EMT and MET states to construct a NSCLC reference EMT-MET state map, on which we projected NSCLC clinical samples to characterize their phenotypic profile in terms of our in vitro EMT-MET analysis. Finally, we extended our mass cytometry time-course analysis to NSCLC cells that underwent various drug treatments (e.g. Erlotinib, Docetaxel) and subsequent withdrawal to augment our EMT-MET state map with drug resistance phenotypic traits. We found that NSCLC resistant cells displayed through time overlapping morphological and cell signaling features with EMT and MET and were able to rebound from short-term drug-induced effects. These data are currently being used to evaluate EMT-related drug resistant cell states detected in pleural effusions during and after the course of treatment in different NSCLC patient therapy time-points.

      Conclusion

      In summary, we provide a framework that can be extended to phenotypically characterize clinical samples with single-cell resolution in the context of in vitro studies showing differential EMT-MET traits related to drug sensitivity. This sets the foundation for developing tools towards evaluating - at a personalized level – disease status and response to treatment in NSCLC patients.

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    OC01 - Opening Ceremony (ID 82)

    • Event: WCLC 2019
    • Type: Opening Ceremony
    • Track:
    • Presentations: 1
    • Now Available
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      OC01.02 - IASLC Distinguished Awards (Now Available) (ID 3553)

      19:00 - 20:30  |  Author(s): Heather A Wakelee

      • Abstract
      • Presentation

      Abstract not provided

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    P1.04 - Immuno-oncology (ID 164)

    • Event: WCLC 2019
    • Type: Poster Viewing in the Exhibit Hall
    • Track: Immuno-oncology
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/08/2019, 09:45 - 18:00, Exhibit Hall
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      P1.04-17 - Phase I/II Study of Nivolumab and Vorolanib in Patients with Refractory Thoracic Tumors (ID 2443)

      09:45 - 18:00  |  Author(s): Heather A Wakelee

      • Abstract

      Background

      Single-agent nivolumab has limited efficacy in thoracic tumors. The antitumor activity of VEGF TKIs is typically attributed to their effect on angiogenesis; however, emerging data suggest these agents can modulate the immune system, especially in the immune suppressive microenvironment. Preliminary results in multiple solid tumors demonstrated clinical benefit when nivolumab was added to anti-angiogenic agents albeit with increased toxicities. Vorolanib was designed to improve the safety profile without compromising efficacy. No dose-limiting toxicities (DLTs) from vorolanib were reported in multiple single-agent phase I trials.

      Method

      NCT03583086 is an ongoing multi-institutional, phase I/II study of nivolumab and vorolanib in patients with thoracic tumors who have failed at least one prior line of therapy. A standard 3+3 dose escalation design was planned with three doses of vorolanib (200, 300, and 400 mg once-daily) and 240 mg nivolumab every two weeks to determine the maximum tolerated dose. Phase II will evaluate the response rate in five cohorts: PD-1/PD-L1 naïve non-small cell lung cancer (NSCLC), PD-1/PD-L1 primary refractory (defined as progression on PD-1/PD-L1 therapy within 12 weeks), NSCLC patients with acquired resistance (achieved at least stable disease and then progressed) to PD-1/PD-L1, thymic carcinoma, and small cell lung cancer patients who have progressed on prior platinum-based chemotherapy. Exploratory correlatives will assess changes in the innate and adaptive immune responses after treatment.

      Result

      Phase I enrolled 10 patients (eight NSCLC and two thymic cancers); one patient was not evaluable for DLT and replaced. No DLTs were observed in three patients at the first dose level of 200 mg. Vorolanib was escalated to 300 mg, and elevated ALT (Grade 3) occurred in two of six patients just beyond the DLT period but deemed clinically significant; thus, 200 mg vorolanib with 240 mg nivolumab is being evaluated in expansion cohorts. The most common adverse events were elevated ALT, AST, and lipase, diarrhea, and fatigue; most were Grade 1/2. Grade 4 hyperglycemia and elevated lipase and Grade 3 elevated serum amylase occurred in one patient each. In seven efficacy-evaluable patients (2 immunotherapy naïve NSCLC; 3 NSCLC with prior immunotherapy; 2 thymic cancer), two partial responses were observed (1 PD-1/PD-L1 naive NSCLC and 1 thymic cancer patient); the NSCLC patient was also PD-L1 negative. Three NSCLC patients with prior PD-1/PD-L1 inhibitors had tumor regression; two of these had acquired resistance and the other was primary refractory to prior immunotherapy.

      Conclusion

      The combination of 200 mg vorolanib and 240 mg nivolumab was generally well tolerated. Clinical activity was observed in both PD-1/PD-L1 naïve patients and those treated with prior immunotherapy. Final phase I results and available phase II data will be presented.

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    P1.14 - Targeted Therapy (ID 182)

    • Event: WCLC 2019
    • Type: Poster Viewing in the Exhibit Hall
    • Track: Targeted Therapy
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/08/2019, 09:45 - 18:00, Exhibit Hall
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      P1.14-32 - Rash and Efficacy in Anaplastic Lymphoma Kinase Positive (ALK+) Non-Small Cell Lung Cancer Patients Treated with Ensartinib (ID 2382)

      09:45 - 18:00  |  Presenting Author(s): Heather A Wakelee

      • Abstract
      • Slides

      Background

      Ensartinib is a potent ALK small molecule tyrosine kinase inhibitor (TKI). In a phase 1/2 study, ensartinib was generally well tolerated and demonstrated good clinical activity in pts with ALK+ non-small cell lung cancer (NSCLC). This post hoc analysis sought to determine the relationship between ensartinib-related rash and clinical benefit.

      Method

      Adverse events (AEs) were coded using MedDRA v15.0; severity was assessed by investigators using NCI CTCAE v4.03. Objective response rate (ORR) and median progression-free survival (mPFS) were explored in the efficacy-evaluable population, which included ALK+ pts receiving ensartinib 225 mg QD who had a postbaseline response assessment.

      Result

      As of Feb 07, 2019, 80 pts were dosed at the phase 3 dose of 225 mg QD and were efficacy evaluable (13 were ALK TKI naive, 37 had received prior crizotinib only, and 30 had received a prior second-generation ALK TKI). Rash was the most common AE observed in 69% of pts, mostly grade 1/2. The rashes started most frequently (33%) at day 7 or 8. The most common types of rash were general rash, rash maculopapular, and rash erythematous. Rash was primarily managed with topical corticosteroids, with some dose reductions, or no intervention at all and rarely led to discontinuation (2% [n=2]). The median duration of rash was 22 days. The ORR and mPFS were better in pts with rash vs those without (ORR, 53% vs 40%; mPFS, 8.6 vs 5.7 mo; P=.0044) (Table). A multivariate Cox proportional hazards model controlling for baseline factor (eg, age, sex, ECOG PS, and prior ALK TKI) revealed a correlation between rash and PFS (HR=0.556; P=.0755). Pts are still being accrued in this study.

      table 1_wclc.jpg

      Conclusion

      Ensartinib was associated with mild to moderate rash that was easily managed. Preliminary findings suggest that rash is potentially associated with better clinical benefit with ensartinib.

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    P1.15 - Thymoma/Other Thoracic Malignancies (ID 184)

    • Event: WCLC 2019
    • Type: Poster Viewing in the Exhibit Hall
    • Track: Thymoma/Other Thoracic Malignancies
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/08/2019, 09:45 - 18:00, Exhibit Hall
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      P1.15-02 - Role of mTOR Inhibitor Everolimus in the Treatment of Metastatic Thymic Epithelial Tumors (ID 2763)

      09:45 - 18:00  |  Author(s): Heather A Wakelee

      • Abstract
      • Slides

      Background

      Optimal treatment for metastatic thymic epithelial tumors (TETs) after progression on platinum-based chemotherapy has yet to be determined. There is emerging evidence to support the use of mTOR inhibitor everolimus in this setting including the recent phase II study by Zucali et al. However, patient selection and identifying predictors of response remains a challenge. Here, we describe a single-center experience with everolimus in TETs and molecular markers associated with response to therapy using a computational biological model (CBM).

      Method

      Data on all patients with advanced TETs who were prescribed everolimus at our institution were retrospectively abstracted from the electronic medical record. Time to treatment failure (TTF) and overall survival (OS) were calculated. Solid Tumor Actionable Mutation Panel (STAMP), a targeted next generation sequencing (NGS) panel, was run on each TET and the results were computationally matched to a cohort of genomically similar TET patients from The Cancer Genome Atlas (TCGA). CBM was used to examine key genomic alterations of TETs correlated with response on everolimus. Responders were defined as having TTF > 6 months.

      Result

      Thirteen patients with TETs, including ten thymomas (T) and three thymic carcinomas (TC) treated with everolimus, were included. All patients had been heavily pre-treated with an average of three prior lines of therapy. Three patients discontinued treatment due to adverse events. The average TTF was 10.8 months in T and 2.6 months in TC with median OS of 205 months (T) and 67.8 months (TC). Molecular data was available for 11 of 13 patients and identified mutations in MAP2K, HRAS and NF1 as key molecular features associated with a response to everolimus. CBM accurately predicted response in 9 of 11 genomically similar TCGA tumors to our patient cohort.

      Conclusion

      Patients with previously treated metastatic TETs appear to benefit from everolimus. Molecular testing of these tumors using targeted NGS panel revealed an association with several key genes, which may help to guide patient selection in the future.

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    P2.01 - Advanced NSCLC (ID 159)

    • Event: WCLC 2019
    • Type: Poster Viewing in the Exhibit Hall
    • Track: Advanced NSCLC
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/09/2019, 10:15 - 18:15, Exhibit Hall
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      P2.01-73 - Outcome Disparities in American Indian/Alaskan Natives with Advanced Stage Lung Cancer (ID 2679)

      10:15 - 18:15  |  Author(s): Heather A Wakelee

      • Abstract
      • Slides

      Background

      Although there have been many advances in the treatment of lung cancer, outcomes for American Indian/Alaskan Natives (AI/AN) have remained poor. AI/AN patients present at a younger age, more advanced stage and have higher lung-cancer attributed mortality rates. While disparities in treatment of early stage lung cancer are well described, the pattern of treatment in advanced stage disease and cancer guideline concordance is incompletely understood.

      Method

      Data was obtained from the National Cancer Institute SEER database from 2000-2013, which was linked with Medicare enrollment and claims data from the Centers for Medicare and Medicaid Services. Patients were included if they were characterized as AI/AN by either SEER or Medicare databases and diagnosed with stage IIIB/IV lung cancer. Demographic data and clinical characteristics were abstracted. Metrics were developed to assess adherence with lung cancer treatment guidelines.

      Result

      Out of 238,439 lung cancer patients, 404 patients had advanced stage disease and were coded as AI/AN in SEER. They were propensity matched by age at diagnosis, year of diagnosis and number of lung cancers to a cohort of white advanced stage patients (N=404). The comparison of the patient characteristics across the two race groups shows that AI/AN patients were more likely to have squamous cell histology, live in smaller urban communities, less likely to be married, and less likely to receive surgery or radiation. Only 20.5% of the advanced lung cancer AI/AN population received appropriate therapy within 90 days of diagnosis compared with 29.5% of the propensity matched white cohort (p = 0.004).

      Conclusion

      AI/AN patients are less likely to receive cancer-directed care such as surgery or radiation than the matched white cohort and less likely to receive appropriate therapy within 90 days of diagnosis. Work is ongoing to evaluate adherence to other metrics such as receipt of appropriate diagnostics and treatment as well as trends in survival.

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    WS06 - Women in Thoracic Oncology Networking Event (ID 355)

    • Event: WCLC 2019
    • Type: Workshop
    • Track: Thymoma/Other Thoracic Malignancies
    • Presentations: 3
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      WS06.01 - Welcome (ID 3828)

      07:00 - 08:00  |  Presenting Author(s): Heather A Wakelee

      • Abstract

      Abstract not provided

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      WS06.02 - Lessons Learned – Women Leaders in Thoracic Oncology (ID 3829)

      07:00 - 08:00  |  Presenting Author(s): Heather A Wakelee

      • Abstract
      • Slides

      Abstract not provided

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      WS06.03 - Networking Table 1: Mentor-Mentee Relationship (ID 3830)

      07:00 - 08:00  |  Presenting Author(s): Heather A Wakelee

      • Abstract

      Abstract not provided

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    YI01 - First Time Attendee Session (ID 107)

    • Event: WCLC 2019
    • Type: Young Investigator Session
    • Track: Young Investigators
    • Presentations: 1
    • Now Available
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      YI01.03 - Making the Most of WCLC: A Guide for First Time Attendees (Now Available) (ID 3692)

      07:00 - 08:30  |  Presenting Author(s): Heather A Wakelee

      • Abstract
      • Presentation
      • Slides

      Abstract

      Congratulations on making the decision to attend the International Association for the Study of Lung Cancer (IASLC) World Conference on Lung Cancer (WCLC)! This is the largest meeting in the world focused entirely on thoracic malignancies and is truly an international and multidisciplinary event. However, it is possible to get lost with so many concurrent sessions and in the sea of thousands of delegates. So having a game plan is critical. You will want to have a roadmap and plan for each day but also allow time for networking and to have some fun. With the virtual meeting available afterwards do not worry too much if you want to be in two places at once. You can be… “virtually.”

      Check out the “First Time WCLC Attendees” tab on the IASLC WCLC2019 conference website for great guidance from Dr. Anne-Marie Baird. To paraphrase her:

      #1 Prepare

      #2 Attend the Young Investigators Symposium

      #3 Check out the Posters

      #4 Network

      #5 Engage with Social Media.

      These are all outstanding suggestions! To help you prepare be sure to look at the program in advance and get a sense of the conference center layout. Each morning there is a Plenary session highlighting key topics with talks given by world leaders. These can be amazing! The top abstracts of the meeting will be presented in the Presidential symposium on Monday morning Sept 9. The conference app (available a week or so before the start of WCLC2019) is a great way to keep track of everything. With so many concurrent sessions it will be important to have the info at your fingertips.

      There is a daily press conference that you can attend or review in the press and media section of the WCLC website. Highlights of the day (HOD) will be presented Mon Sept 9 and Tues Sept 10 from 10:30-12 of the conference and also included in emails and on the website. Checkout the daily newspaper (WCLC Daily News) for more highlights. Also you may want to follow everything that is happening on social media!

      IASLC is active on: Twitter, Facebook, LinkedIn, YouTube, Instagram

      Important Hashtags for lung cancer #LungCancer, #CureMESO, #NSCLC, #SCLC, #CancerResearch, #Oncology, #clinicaltrials

      IASLC 2019 World Conference on Lung Cancer – Social Details:

       Official Conference Hashtag: #WCLC19

       Official Hashtag of Lung Cancer Social Media Community: #LCSM

      The IASLC operates a social media booth at each WCLC for new users to learn about social media, get a tip-sheet and take photos with special branded backdrop (which is really fun)!

      As you look at the program you will see there is a great mix of education sessions, workshops and new data presentations. You will likely want to attend a mix of all of these. The education sessions may be a focus since those will include global experts summarizing particular topics and future predictions. It can be a bit tricky to understand the significance of some of the new data without knowing the background and the education sessions will help with that knowledge. It is also great to go to some of the mini-orals (MA) and oral (O) sessions to hear the latest research, particularly in your areas of interest. The mini-orals can be tricky as each one goes by fast so be ready! Again, plan in advance.

      As Dr. Baird points out, the poster/networking sessions are really wonderful. A lot of critical data that might not be as “flashy” is buried in the posters and you are likely to learn a lot. Even more importantly you will have a chance to network and find out who around the world is focusing in the same areas where you have interests. There are 2 poster sessions each day. The poster sessions are particularly great because you actually get to interact with people. If you see someone you want to talk to at the poster session do not be intimidated if they happen to be a “name” you have read multiple times in key papers. Everyone is excited to meet eager people working to help fight lung cancer!

      The importance of networking cannot be over-emphasized. Getting to know the field and others who share your passion for fighting lung cancer and other thoracic malignancies can make a tremendous impact on your future academic career. Branch out and meet people in other disciplines and from other parts of the world. Having a common interest in fighting lung cancer can lead to some strong connections and it is incredibly fun to attend future conferences knowing that you will get to connect with friends you met at your first IASLC WCLC. Important collaborations can also be started including international efforts. If you are still in training this networking time is also critical to your future job hunting!

      Remember to have FUN! Sign up and attend the IASLC social events. These involve good food, great music and sometimes dancing and most importantly a real opportunity to network.

      Saturday – Opening Ceremony and Welcome Reception

      Monday - IASLC Foundation Road to Hope gala

      Tuesday - Closing Ceremony

      After running around at the conference there will be times you just want to sit and relax. Fortunately there is an IASLC membership lounge in the exhibit hall open during exhibit hours. All members are invited to use the space for meetings, to sit for a few minutes, and to learn more about the IASLC and its committees. More details can be found here: https://wclc2019.iaslc.org/networking_opportunities/

      Also, make some time before or after the conference to be a tourist in the local region. Most convention centers are fairly similar, but thinking about the last 3 IASLC WCLC conferences you can imagine how Yokohama, Toronto and Barcelona are all very different and fabulous places to explore.

      Enjoy your first IASLC WCLC and hopefully you will plan to make it an annual event!

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