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K. Nackaerts



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    OA 02 - Mesothelioma: Challenges For New Treatment (ID 653)

    • Event: WCLC 2017
    • Type: Oral
    • Track: Mesothelioma
    • Presentations: 1
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      OA 02.01 - Randomized Phase II Study of Anetumab Ravtansine or Vinorelbine in Patients with Malignant Pleural Mesothelioma (ID 9377)

      11:00 - 12:30  |  Author(s): K. Nackaerts

      • Abstract
      • Presentation
      • Slides

      Background:
      Anetumab ravtansine (BAY 94-9343) is a novel fully human anti-mesothelin IgG1 antibody conjugated to the maytansinoid tubulin inhibitor DM4. We report the results of a randomized phase II trial of anetumab ravtansine compared to vinorelbine in patients with advanced malignant pleural mesothelioma (MPM) who have high mesothelin expression and have progressed on platinum/pemetrexed-based first-line chemotherapy (NCT02610140).

      Method:
      Patients (≥18 years) with locally advanced or metastatic MPM with progressive disease following first-line treatment with pemetrexed-based chemotherapy, with or without bevacizumab, were eligible. Patients were pre-screened based on obligatory tumor staining for mesothelin as determined by the Ventana MSLN (SP74) immunohistochemistry assay. The primary efficacy endpoint was progression-free survival (PFS) per central radiologic review using modified RECIST criteria for MPM. Secondary objectives included overall survival, tumor response, and safety. Patients were randomized in a 2:1 ratio to anetumab ravtansine 6.5 mg/kg Q3W IV or vinorelbine 30 mg/m[2] QW IV.

      Result:
      A total of 166 patients were randomized to anetumab ravtansine and 82 to vinorelbine; 3 and 10 patients, respectively, not receiving treatment were included for efficacy but not safety assessments. The treatment arms were evenly balanced, with 73% male, 64% ECOG performance status 1, 96% epithelioid histology, and a mean 2.5 (±2.4) months since last progression. The median duration of treatment (anetumab vs vinorelbine) was 12.6 weeks (range 3-61) vs 13.0 weeks (range 1-43). Treatment-emergent grade (G) ≥3 adverse events (AEs) were seen in 85 (52.1%) and 53 (73.6%) of patients, respectively. G3/G4 neutropenia (22.2%/16.7%) occurred in the vinorelbine arm whereas corneal epitheliopathy (39.3% all grade, 1.8% G3) was distinct for the anetumab ravtansine arm. Serious AEs (any grade) were similar; 52 (31.9%) vs 25 (34.7%). Treatment-emergent AEs leading to dose modification were 42.9% in the anetumab ravtansine arm and 80.6% in the vinorelbine arm. There was one treatment-related G5 event in each arm. Median PFS was 4.3 months (95% CI:4.1, 5.2) for anetumab ravtansine vs 4.5 months (4.1, 5.8) for vinorelbine; hazard ratio 1.22 (0.85, 1.74), p=0.859. Fourteen (8.4%) patients in the anetumab ravtansine arm had an objective response vs 5 (6.1%) in the vinorelbine arm, with no complete responses. Interim median overall survival was 10.1 mo (7.6, -) vs 11.6 mo (7.7, 12.5), respectively, p-value 0.721.

      Conclusion:
      In relapsed MPM, anetumab ravtansine was not superior to vinorelbine with respect to PFS.

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    P1.13 - Radiology/Staging/Screening (ID 699)

    • Event: WCLC 2017
    • Type: Poster Session with Presenters Present
    • Track: Radiology/Staging/Screening
    • Presentations: 1
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      P1.13-007 - Is Central Lung Tumor Location Really Predictive for Occult Mediastinal Nodal Disease in (Suspected) NSCLC Staged cN0 on PET-CT?  (ID 8779)

      09:30 - 16:00  |  Author(s): K. Nackaerts

      • Abstract

      Background:
      Based on a 20-30% prevalence of occult mediastinal disease, current guidelines recommend preoperative invasive mediastinal staging in patients with central tumour location and negative mediastinum on PET-CT. A uniform definition of central tumour location is lacking. Our objective was to determine the best definition in predicting occult mediastinal disease.

      Method:
      A single institution prospective database was queried for patients with (suspected) NSCLC staged cN0 after PET-CT and referred to invasive staging and/or primary surgery. We evaluated 5 definitions of central tumour location (table 1).

      Result:
      Between 2005 and 2015, 822 patients were eligible. Radio-occult lesions were excluded from analysis (n=9). Preoperative histology was NSCLC in 49% and unknown in 51%. The lesion was subsolid in 7%. Tumour stage was cT1, cT2, cT3 and cT4 in 43%, 28% 17% and 11%, respectively. Invasive mediastinal staging (EBUS and/or mediastinoscopy) was performed in 31%. Surgical resection was performed in 97%, a median of 5 (IQR 3-6) nodal stations were examined. The final pathology was squamous NSCLC, non-squamous NSCLC, or other in 38%, 54% and 7%, respectively. Any nodal upstaging was found in 21% (13% pN1 and 8% pN2-3). Central tumour location demonstrated, compared to peripheral location, a 4 times higher risk for any nodal upstaging but not for N2-3 upstaging (table 1).

      Conclusion:
      When modern PET-CT fusion imaging points at clinical N0 NSCLC, the prevalence of occult mediastinal nodal disease was only 8% in our patient cohort. None of the five definitions of centrality we studied was predictive for occult pN2-N3. Overall nodal upstaging was 21%, however, and all definitions of centrality then had discriminatory value. These data question whether the indication of preoperative invasive mediastinal staging should be based on centrality alone. Table 1 Figure 1



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    P3.09 - Mesothelioma (ID 725)

    • Event: WCLC 2017
    • Type: Poster Session with Presenters Present
    • Track: Mesothelioma
    • Presentations: 1
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      P3.09-003 - Heart Radiation Dose as a Risk Factor for Dyspnea Worsening After Multimodality Treatment for NSCLC and MPM: An Exploratory Analysis (ID 10496)

      09:30 - 16:00  |  Author(s): K. Nackaerts

      • Abstract

      Background:
      The purpose of our study was to quantify the influence of heart dose on the early and late onset of dyspnea in a cohort of non-small cancer (NSCLC) and malignant pleural mesothelioma (MPM) patients having multimodality treatment including radiotherapy (RT).

      Method:
      In 121 patients with multimodality-treated NSCLC and MPM the maximal dyspnea score (CTCAE 4.0) before RT, at an early (<6 months) and a late (7-12 months) time point were obtained. Included patients needed to be clinically and radiologically progression-free 9 months after the end of RT. The difference (Δ) between the maximal dyspnea at <6 months and at 7-12 months with the pre-RT dyspnea was calculated.

      Result:
      Forty-four percent (50/113) of the patients developed an early worsening of at least 1 point in their dyspnea score (Δdyspnea >1) after the end of RT. Independent predictors of an early worsening were the mean heart dose (MHD) (for Δdyspnea >1: OR=1.03, p=0.04) and the dyspnea score before RT (for Δdyspnea >1: OR=0.40, p=0.0001; for Δdyspnea >2: OR=0.35, p=0.05). At the later time point, only the dyspnea score before RT (OR: 0.40, p=0.001) was identified as predictor of Δdyspnea >1.

      Conclusion:
      Our results, albeit exploratory, suggest that heart dose may play a role in the early worsening of the dyspnea in a heterogeneous cohort of patients having multimodality treatment including RT, whereas baseline dyspnea plays a major role for both early and later worsening.