Virtual Library

Start Your Search

Diana Saravia



Author of

  • +

    MA19 - Genomic Markers of IO Response (ID 922)

    • Event: WCLC 2018
    • Type: Mini Oral Abstract Session
    • Track: Immunooncology
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/25/2018, 15:15 - 16:45, Room 201 BD
    • +

      MA19.04 - The Clinical Implication of Frameshift Indel Mutation Burden in Non-Small Cell Lung Cancer (NSCLC) (ID 12592)

      15:35 - 15:40  |  Author(s): Diana Saravia

      • Abstract
      • Presentation
      • Slides

      Background

      Tumor mutational burden (TMB) has been proposed as a potential predictive marker for immune checkpoint inhibitor (ICI) response in many cancers, including NSCLC. Recently, research has revealed frameshift indel (fsindel) of all mutations to be significantly associated with ICI response in melanoma patients. However, little is currently known regarding its clinical implication in NSCLC patients treated with PD1/PD-L1 inhibitors (ICIs).

      a9ded1e5ce5d75814730bb4caaf49419 Method

      Next generation sequencing of 324 genes (FoundationOneTM) was used to derive fsindel burden and TMB. A total of 128 patient data with NSCLC treated with ICIs were analyzed from Northwestern University (N=68) and the University of Miami (N=60). A total of 128 patients were divided into two groups with 0 fsindel (FS-) and more than 1 fsindel (FS+). Progression free survival (PFS) and overall survival (OS) were compared between FS+ and FS- groups. PFS and OS outcomes of TMB high group (H-TMB, upper¼) and TMB low group (L-TMB, lower¼) were also compared.

      4c3880bb027f159e801041b1021e88e8 Result

      figure 1.jpg

      Among 128 patients, 51.6% belonged to FS+ group (N=66). Between FS-/FS+ groups, there were no significant differences in mean age (66.2/66.0) and performance status (0.9/0.9). Lines of ICIs used in the FS-/FS+ groups were 1st (19/19%), 2nd (47/56%), 3rd (24/11%), and 4th line or more (10/14%). FS+ group had significantly longer PFS compared with FS- group (median 6.2/2.7 months, P=0.02, Figure 1). No significant difference in OS was seen between the two groups (median 16.8/11.2 months, P=0.70). In contrast, however, H-TMB did not show any significant difference in PFS (median 5.6/4.0 months, P=0.14) and OS (median 15.8/15.1 months, P=0.69) compared to L-TMB.

      8eea62084ca7e541d918e823422bd82e Conclusion

      This is the first report to illustrate an association between fsindel and outcome in patients with NSLC treated with ICIs. Our findings suggest its potential role as a predictive marker for immunotherapy.

      6f8b794f3246b0c1e1780bb4d4d5dc53

      Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.

      Only Active Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login or select "Add to Cart" and proceed to checkout.

  • +

    P1.01 - Advanced NSCLC (Not CME Accredited Session) (ID 933)

    • Event: WCLC 2018
    • Type: Poster Viewing in the Exhibit Hall
    • Track:
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/24/2018, 16:45 - 18:00, Exhibit Hall
    • +

      P1.01-68 - Correlation of the Lung Immune Prognostic Index (LIPI) and PDL1 Status with Outcomes for Immune Checkpoint Inhibitors in Advanced NSCLC Patients (ID 14256)

      16:45 - 18:00  |  Author(s): Diana Saravia

      • Abstract

      Background

      Baseline LIPI, based on derived NLR (neutrophils/[leucocytes-neutrophils]) and lactate dehydrogenase (LDH) was associated with outcomes for immune checkpoint inhibitors in advanced NSCLC patients. We assessed the correlation between LIPI and PDL1 for ICI outcomes in NSCLC.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      Baseline dNLR and LDH and clinical data were retrospectively collected in advanced NSCLC patients, treated with PD1/PDL1 +/- CTLA4 inhibitors from Nov. 2012 to Mar. 2018, in a multicentric cohort (N=794) from 11 centers. LIPI stratified 3 groups: good (dNLR<3+LDH<upper limit of normal (ULN), intermediate (dNLR>3 or LDH>ULN), poor risk (dNLR>3+LDH>ULN). PDL1 positivity was defined as ≥ 1% tumor cells expression by immunohistochemistry.

      4c3880bb027f159e801041b1021e88e8 Result

      476 patients (60%) were male, 693 (87%) smokers, 695 (88%) had PS ≤1, with median age 65; 576 (73%) had nonsquamous histology. PDL1 was ≥ 1% in 195 (70%) patients, negative in 82 (30%), and unknown in 517. The median of prior lines was 1 (0-11). The median PFS and OS were 4 months (m) [95% CI 4-5] and 12 m [10-15]. dNLR was>3 in 276 (35%) and LDH>ULN in 290 (37%) patients. LIPI stratified 349 patients as good (44%), 323 (41%) as intermediate and 121 (15%) as poor LIPI risk groups. LIPI was an independent factor for OS (table) and PFS (HR 2.58; CI 1.3-5.2, P=0.02). ≥ 1% PDL1 and ≥ 50% PDL1 were not correlated with OS and PFS. Median OS for good, intermediate, and poor LIPI risk groups were 21 m [17-23], 11 m [9-14] and 4 m [2-6], respectively (P=<0.0001). Median PFS for good, intermediate, and poor risk was 5 m [5-7], 4 m [3-5], and 2 m [1-3], respectively (P=0.0005). No differences were observed in LIPI groups according to the PDL1 expression.

      Multivariate analysis for OS

      HR

      95% CI

      P value

      Immunotherapy line

      >2

      2.117

      0.641

      6.992

      0.219

      N# Metastasis sites

      ≥2

      1.242

      0.727

      2.121

      0.428

      Performance status

      ≥2

      2.141

      1.059

      4.332

      0.034

      Albumin

      >35 g/dL

      0.867

      0.507

      1.48

      0.6

      LIPI

      Intermediate

      Poor

      1.697

      4.178

      0.917

      1.956

      3.142

      8.925

      0.001

      PDL1 IHC

      ≥1%

      0.713

      0.406

      1.252

      0.239

      8eea62084ca7e541d918e823422bd82e Conclusion

      Baseline LIPI is associated with ICI outcomes in advanced NSCLC, regardless the PDL1 expression. LIPI should be evaluated in prospective clinical trials.

      6f8b794f3246b0c1e1780bb4d4d5dc53

  • +

    P2.15 - Treatment in the Real World - Support, Survivorship, Systems Research (Not CME Accredited Session) (ID 964)

    • Event: WCLC 2018
    • Type: Poster Viewing in the Exhibit Hall
    • Track:
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/25/2018, 16:45 - 18:00, Exhibit Hall
    • +

      P2.15-23 - Are there Ethnic Disparities in the Clinical Outcomes of Non-Small Cell Lung Cancer Hispanic Patients Treated with Immunotherapy? (ID 12359)

      16:45 - 18:00  |  Author(s): Diana Saravia

      • Abstract
      • Slides

      Background

      Immunotherapy outcomes in non-small cell lung cancer (NSCLC) are widely available thanks to studies that got the approval of PD-1/PD-L1 inhibitors. However a careful review of ethnicity can find that most of the studies were done in Non-Hispanic White or Asian populations. There is little known about the outcomes in Hispanics (H). It is well known that Hispanics (H) in the US seem to have a lower age-adjusted mortality in NSCLC and have a different gene expression profile than NHW with higher prevalence of EGFR mutations.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      We reviewed clinical outcomes in 216 H pts with NSCLC stage IV treated with atezolizumab, nivolumab or pembrolizumab at 4 large cancer centers (Memorial Cancer Institute, University of Miami and Moffitt Cancer Center all of them in Florida (US), and the National Cancer Institute in Peru. These patients have failed at least one line of chemotherapy previously. All of these patients did not have actionable genes (EGFR. ALK, ROS-1). We assessed overall response rate ORR (CR+PR) as main objective and disease control rate (DCR: ORR+SD), median PFS (progression free survival) & overall survival (OS) and PFS at 6m and 12m as secondary objectives.

      4c3880bb027f159e801041b1021e88e8 Result

      Most of the pts were males: 116 (54%), 82% adenocarcinomas and the median age was 65 years (range: 37-88y). The ORR was 16% and the DCR that shows the clinical benefit was 67%. ORR and DCR were similar in adenocarcinomas (20%/68%) and squamous cell carcinomas (17%/64%). The progression free survival (PFS) at 6 months (m) and 12m were 80% and 56% respectively. Median PFS 14.5m and median overall survival were 19m, respectively.

      8eea62084ca7e541d918e823422bd82e Conclusion

      ORR for NSCLC pts treated with immunotherapy is 16% in Hispanics treated at 4 cancer centers compared to an expected 20% ORR for NHW as reported in the literature. Therefore it appears that Hispanics might not have a benefit from immunotherapy to the extent that NHWs do. We need a larger cohort and prospective studies to validate these findings.

      6f8b794f3246b0c1e1780bb4d4d5dc53

      Only Active Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login or select "Add to Cart" and proceed to checkout.