Virtual Library

Start Your Search

Alan Spatz



Author of

  • +

    MA16 - Prioritizing Use of Technology to Improve Survival of Lung Cancer Subgroups and Outcomes with Chemotherapy and Surgery (ID 142)

    • Event: WCLC 2019
    • Type: Mini Oral Session
    • Track: Treatment in the Real World - Support, Survivorship, Systems Research
    • Presentations: 1
    • Now Available
    • +

      MA16.09 - Clinical Practice and Outcomes in Patients with Stage III Unresectable Non-Small-Cell Lung Canceran Academic Centre, Canada (Now Available) (ID 818)

      15:45 - 17:15  |  Author(s): Alan Spatz

      • Abstract
      • Presentation
      • Slides

      Background

      The prognosis of patients with stage III unresectable non-small cell lung (NSCLC) cancer is poor: five-year OS is only 19-24% for stage IIIA and 7- 9% for stage IIIB. In light of the approval of immunotherapy maintenance treatment, after completion of CRT, we undertook a retrospective study to characterize management and report outcomes of patients with stage III, unresectable NSCLC treated with chemoradiation (CRT) at the Jewish General Hospital, Montreal.

      Method

      Patients diagnosed with stage III unresectable NSCLC,and treated with combined CRT, either concurrent (cCRT) or sequential (sCRT) treatment,between January 2007 to December 2018 were included in the study. Overall survival was calculated using the Kaplan-Meier approach and calculated from the start of radiotherapy. Physician defined progression-free survival was calculated from the start of radiotherapy until documented progression based on radiologic assessment. A multivariate analysis using Cox regression was carried out to assess clinical factors impacting survival.

      Result

      134/263 patients were deemed unresectable and received combined CRT. 124/134 (92.5%) received CRT as initial treatment and 10(7.5%) received CRT after progression to stage 3 post surgery for an earlier stage NSCLC.114/134 received cCRT and 20/134 received sCRT. Patients on cCRT were significantly younger with a slight prevalence of non-squamous histology and had N1 or single station N2 disease.Median OS (mOS) was 18.7 months (95%CI, 12.4-24.8) for the overall cohort; mOS in cCRT of 23.3 months (95%CI,14.3-32.2) was significantly better compared to 11.33 months with sCRT (95% CI, 10.2-24.8 p=0.01). PFS was slightly better in patients with cCRT (7.97mo, 95%CI 1.75-11.18) compared to sCRT (5.26mo, 95% CI 4.06-6.48 p=0.08).86/134 (64%) progressed and received subsequent therapy: 49 (57%)-chemotherapy alone, 15 (17.4%)–radiation alone, 13 (15.1%)-immunotherapy and 9 (10.5%)-targeted therapy.In multivariate analysis, the tumor size (HR 1.5, 95%CI 1.08-1.97) and nodal status (HR 2.5, 95%CI 3.34-4.74) were the only prognostic factors for OS. Gender, age, ECOG, smoking status, histology, chemotherapy protocol, subsequent therapy, mutation status and cCRT were not statistically significantin multivariate analysis. cCRT was not significant, likely due to patient selection.

      Conclusion

      Unresectable stage III NSCLC is a heterogenous group that is challenging to manage. Combined CRT has beenthe standard of care for this group of pts. In our patient cohort, a trend of improved survival was seen in the cCRT group. Tumor size and nodal status were prognostic factors for OS. Future studies evaluating survival with newer IO therapies is of interest.

      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 (ID 158)

    • Event: WCLC 2019
    • Type: Poster Viewing in the Exhibit Hall
    • Track: Advanced NSCLC
    • Presentations: 2
    • Now Available
    • Moderators:
    • Coordinates: 9/08/2019, 09:45 - 18:00, Exhibit Hall
    • +

      P1.01-52 - Cell-Free Tumor DNA (ctDNA) Utility in Detection of Original Sensitizing and Resistant EGFR Mutations in Non-Small Cell Lung Cancer (NSCLC) (Now Available) (ID 809)

      09:45 - 18:00  |  Author(s): Alan Spatz

      • Abstract
      • Slides

      Background

      With the use of personalized therapy the need for repeat biopsies in lung cancer patients (pts) has increased. For most lung cancer pts, a tissue biopsy can be quite challenging and potentially risky.The aim of this study was to evaluate the utility of ctDNA to detect the EGFR original mutation (OM) and to identify the T790M resistance mutation in advanced NSCLC pts who received EGFR-TKI.

      Method

      This is a prospective cohort study utilizing theCobas EGFR ctDNA testing kit V2 in pts with confirmed EGFR-mutant advanced NSCLC by tissue biopsy. The blood was obtained from 66 pts at 4 time points: baseline, time of 1st CT, time of progression, and 1 month after starting new treatment.

      Result

      From January 2017 to January 2019, 66 pts were enrolled in the study, of which 41(62%) had an exon 19 deletion and 25(38%) had an exon 21 mutation. 23/66 pts were TKI naive and 43/66 were already on TKI treatment. Adequate ctDNA was found in the plasma of 97% of cases. The OM was identified in 42 % of pts at first blood test with higher detection rates in TKI naïve pts 12/23(52%) compared to 16/43(37%) in TKI group.

      Best response to first line TKI was evaluated in 64 pts; in 56 (88%) pts, disease was controlled (CR+PR+SD) with TKI, in 8 (12%) pts the treatment had failed and was discontinued. A significant correlation between OM detection and response to first line TKI was found (p =0.05) with higher detection rate in non-responders 6/8(75%) compared to responders 21/56 (38%). In TKI naïve pts OM was detected in 4/5(80%) of non-responders and in TKI group in 2/3 (67%) pts.

      The resistance mutation (T790M) was detected in 12/66 (18%) pts. All 12 (100%) pts initially responded to TKI and OM was no longer detected. Median duration of TKI until progression was 25.5 (SD 12.7) mo. The OM re-occurred in 11/12 (92%) at the time of progression.

      Conclusion

      ctDNA can be noninvasively assessed in the circulation and be used to monitor responses to treatment and detect development of secondary resistance. The re-occurrence of OM on repeat liquid biopsy seems to be a sign of resistance to first line treatment. In the future, instead of extensive imaging and invasive tissue biopsies, ctDNA test by NGS panel could be used to find other mutations and to guide cancer treatment decisions.

      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.

    • +

      P1.01-99 - EGFR-Wild Type Patients Responding to TKI: Revisiting Pathology with Newer Technology (Now Available) (ID 2655)

      09:45 - 18:00  |  Author(s): Alan Spatz

      • Abstract
      • Slides

      Background

      Molecular testing of lung adenocarcinoma is now considered standard of care and an integral component of the diagnostic algorithm. Technology platforms are rapidly evolving and becoming more sensitive, specific, comprehensively cover clinically relevant actionable mutations and adapted for low input of limiting samples. Targeting EGFR receptors is an important treatment modality in EGFR-mutant patients. However, despite demonstrated benefit in overall survival (OS) and progress free survival (PFS) wild-type patients are deemed to be not suitable for TKIs therapy. Data on long-term responders to TKI among EGFR-wild type patients is limited and requires investigation. Herein, we re-tested samples, which tested negative for EGFR by in-house real-time PCR testing, of patients who responded to TKIs in order to explore the possible indicators of response using FoundationOne NGS assay.

      Method

      This is a prospective cohort study of EGFR-wild-type patients by in-house testing (period 2004-2016, real-time PCR) who were light or non-smokers and were treated with TKI (Erlotinib) at the single Academic Centre of the Jewish General Hospital. Erlotinib was given to patients in first- or second-line after failure of systemic chemotherapy. The Formalin Fixed Paraffin Embedded tissue (FFPE) of samples were sent to be analyzed by FoundationOne assay.

      Result

      Nineteen samples of patients who were treated with Erlotinib were sent to be tested. 16/19 were treated with TKI for ≥6 mo, 11/16 responded to TKI (defined as staying on treatment over 100 days with median response of over 600 days). Only 2/11 responders received erlotinib in first line, the 9/11 received it after progressing on first-line platinum-based doublets. Sensitizing EGFR mutations were found in 4/11 responders, which can be explained by increased coverage and sensitivity of the NGS platform. Among the remaining 7 patients that were confirmed to be negative by FoundationOne test, one patient had a rearrangement of EGFR (truncation), and two had RBM10 mutations, one an ERBB2 amplification, and 3 had MAP3K1 mutations as well as multiple novel alterations of unknown significance. These alterations may shed light to patient responses and require further exploration.

      Conclusion

      The algorithms for molecular testing is based on the specimen pathology and local clinical and laboratory circumstances. There are a multitude of platforms available for somatic mutational and fusion testing and these are rapidly evolving with availability and accessibility of NGS. Comprehensive NGS panels and multidimensional data sets will widen our understanding of genetic dependencies associated with responses and pave the road to new therapeutic avenues.

      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.