Author of

• 25941

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  P2.04 - Immunooncology (Not CME Accredited Session) (ID 953)

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

  • 26990

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    P2.04-14 - Tumor Mutational Burden Assessed by a Targeted NGS Assay Predicts Benefit from Immune Checkpoint Inhibitors in Non-Small Cell Lung Cancer  (ID 14516)

    16:45 - 18:00  |  Author(s): Spasenija Savic
    • Abstract

    Background
    

    Immune checkpoint inhibitors (ICI) improve overall survival in non-small cell lung cancer (NSCLC) in the 2^nd-line setting and lead to prolonged disease control in a subgroup of patients (pts). Robust predictive biomarkers for ICI are highly desired. In an exploratory analysis of the CheckMate 026 study, high tumor mutation burden (TMB) assessed by whole-exome sequencing was associated with improved outcome of pts treated with nivolumab.

    a9ded1e5ce5d75814730bb4caaf49419 Method
    

    From our institutional database, 41 pts with metastatic NSCLC were included in this study and identified as either having clinical benefit (CB; defined as complete/partial response (CR/PR) or stable disease (SD)) or having no clinical benefit. TMB was assessed using a targeted NGS assay that simultaneously detects variants in all coding regions / sequences of 409 cancer-related genes (Oncomine Tumor Mutation Load Assay, Thermo Fisher Scientific, Waltham, MA, USA). TMB values were normalized to tumor cell content. The correlation between TMB and CB rate was assessed. Mann-Whitney test was used and differences were considered significant at a p-value <0.05.

    4c3880bb027f159e801041b1021e88e8 Result
    

    Of 41 pts (mean age 63.7 years), 73% were male, 87.8% smokers and 71% had adenocarcinoma histology. Nivolumab was the most frequently used ICI (70.7%), and it was most commonly used in the 2^nd-line setting (61.0%). PR was observed in 29.2% of patients, and SD in 14.6%. CB rate was 43.8%. The median number of genomic mutations per Megabase (Mb) was 8.81. In pts with CB, median TMB with 11.52 mutations per Mb was significantly higher than in pts without response to therapy (7.71 mutations per Mb; p=0.02).

    8eea62084ca7e541d918e823422bd82e Conclusion
    

    TMB as determined by a targeted NGS panel comprising the coding regions of 409 cancer-related genes can reliably predict clinical benefit from ICI. These results need further confirmation due to limited sample size of this study. We are currently analyzing a second independent cohort, and results will be presented during the meeting.

    6f8b794f3246b0c1e1780bb4d4d5dc53

• 25971

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  P3.17 - Treatment of Locoregional Disease - NSCLC (Not CME Accredited Session) (ID 983)

  • Event: WCLC 2018
  • Type: Poster Viewing in the Exhibit Hall
  • Track:
  • Presentations: 1
  • Moderators:
  • Coordinates: 9/26/2018, 12:00 - 13:30, Exhibit Hall

  • 27805

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    P3.17-13 - SAKK 16/14: Durvalumab in Addition to Neoadjuvant Chemotherapy in Patients with Stage IIIA(N2) NSCLC — A Multicenter Single-Arm Phase II Trial. (ID 14517)

    12:00 - 13:30  |  Author(s): Spasenija Savic
    • Abstract

    Background
    

    Improving the outcome of locally advanced non-small cell lung cancer (NSCLC) is one of the major challenges in thoracic oncology. SAKK substantially contributed to establish a standard of care for patients with stage III NSCLC: The trial SAKK 16/96 established neoadjuvant chemotherapy with three cycles of cisplatin and docetaxel. The randomized trial SAKK 16/00 showed no benefit by adding neoadjuvant radiotherapy as third treatment modality. Our results consistently showed a 5-year overall survival (OS) of 37%. Recently, the PACIFIC trial showed significantly improved progression-free survival for durvalumab as consolidation therapy after definitive chemoradiotherapy in unresectable stage III NSCLC.

    a9ded1e5ce5d75814730bb4caaf49419 Method
    

    This is a single-arm phase II clinical trial designed to evaluate the addition of perioperative immunotherapy with durvalumab to the previously established standard of care for stage IIIA(N2) patients. Eligible patients with WHO performance status 0-1 and age of 18-75 years must have pathologically proven NSCLC stage IIIA(N2) (T1-3 N2 M0) according to the 7th edition of the TNM classification, irrespective of histological subtype, genomic aberrations or PD-L1 expression status. Tumor tissue has to be available for the mandatory translational research. Patients whose tumor is deemed resectable at diagnosis receive three cycles of chemotherapy with cisplatin 100 mg/m² and docetaxel 85 mg/m²every three weeks followed by two cycles of durvalumab 750 mg every two weeks. Following surgery, patients will be treated with durvalumab 750 mg every two weeks for 12 months. The primary endpoint of the trial is event-free survival at 12 months. Secondary endpoints include OS, objective response, nodal down-staging, complete resection, pattern of recurrence and toxicity. Additionally, a large translation research program accompanies the trial investigating potential predictive biomarkers of anti-PD-L1 therapy.

    Based on the data of first 25 operated patients and given that the results showed that their 30-day post-operative mortality is less than 10%, according to the decision rule described in the protocol of the trial there is no reason for further detailed safety analysis (evaluated by an IDMC) and thus shall continue as per protocol.

    4c3880bb027f159e801041b1021e88e8 Result
    

    "Section not applicable"

    8eea62084ca7e541d918e823422bd82e Conclusion
    

    "Section not applicable"

    6f8b794f3246b0c1e1780bb4d4d5dc53