Virtual Library

Start Your Search

A. Hackshaw



Author of

  • +

    MO07 - NSCLC - Targeted Therapies II (ID 114)

    • Event: WCLC 2013
    • Type: Mini Oral Abstract Session
    • Track: Medical Oncology
    • Presentations: 1
    • +

      MO07.11 - A randomised placebo-controlled multicentre phase II trial of erlotinib plus whole brain radiotherapy for patients with advanced non-small cell lung cancer with multiple brain metastases (TACTIC) (ID 2305)

      17:15 - 17:20  |  Author(s): A. Hackshaw

      • Abstract
      • Presentation
      • Slides

      Background
      Median survival of non-small cell lung cancer (NSCLC) patients with brain metastases is poor. We examined concurrent erlotinib and whole brain radiotherapy (WBRT) followed by maintenance erlotinib in patients with untreated brain metastases, given the potential radiosensitising properties of erlotinib and its direct effect on brain metastases and systemic activity.

      Methods
      Eighty NSCLC patients with KPS≥70 and multiple brain metastasis were randomised to placebo (n=40) or erlotinib (100mg, n=40) given concurrently with WBRT (20 Gy in 5 fractions). Following WBRT, patients continued with placebo or erlotinib (150mg) until disease progression. The primary end-point was neurological progression-free survival (nPFS).

      Results
      Fifteen patients (37.5%) from each arm were alive and without neurological progression 2 months after WBRT. Median nPFS was 1.6 months in both arms; nPFS HR 0.95 (95% CI, 0.59-1.54; p=0.84). Median overall survival (OS) was 2.9 and 3.4 months in the placebo and erlotinib arms; HR 0.95 (95% CI, 0.58-1.55; p =0.83). The frequency of EGFR mutations was low with only 1 out of 35 (3%) patients with available samples had activating EGFR-mutations. Grade 3/4 adverse event rates were similar between the two groups (70% in each arm), except for rash 20% (erlotinib) vs. 5% (placebo), and fatigue 17% vs. 35%. No significant QoL differences were found.

      Conclusion
      Our study showed no advantage in nPFS or OS for concurrent erlotinib and WBRT followed by maintenance erlotinib in patients with predominantly EGFR wild-type NSCLC and multiple brain metastases. Future studies should focus on the role of erlotinib with or without WBRT in patients with EGFR mutations.

      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.

  • +

    MO09 - Mesothelioma I (ID 120)

    • Event: WCLC 2013
    • Type: Mini Oral Abstract Session
    • Track:
    • Presentations: 1
    • +

      MO09.02 - A Randomised Phase II trial of Pegylated Arginine Deiminase in patients with Malignant Pleural Mesothelioma (ID 1355)

      16:20 - 16:25  |  Author(s): A. Hackshaw

      • Abstract
      • Presentation
      • Slides

      Background
      Preclinically, arginine deprivation has shown activity as a novel antimetabolite strategy for MPM patients who are deficient for the rate-limiting enzyme in arginine biosynthesis argininosuccinate synthetase (ASS1). Here, we examine the efficacy and safety of the arginine-lowering agent ADI-PEG20 (Polaris Group, San Diego, US) among patients with MPM.

      Methods
      We performed a multicentre randomised phase II clinical trial, based on patients with good performance status (0 or 1), non-resectable disease, ASS1-deficient MPM, and measurable disease. Patients were randomized 1:2 to receive best supportive care (BSC) or BSC+ADI-PEG20, stratified by: gender, histology (sarcomatoid versus non-sarcomatoid), prior treatment (chemonaive or previous platinum combination therapy), and centre. The primary endpoint, progression-free survival (PFS), is assessed by modified RECIST, and secondary endpoints include overall survival, tumor response rate, and toxicity. Translational endpoints included measurement of plasma arginine, citrulline and ADI-PEG20 antibody levels, assessment of metabolic response by [18F]Fluorodeoxyglucose Positron Emission Tomography (FDG-PET) and ASS1 methylation status using Illumina’s 450K DNA methylation array. The target sample size was estimated to detect a PFS hazard ratio of 0.60. [Trial funded by Cancer Research UK].

      Results
      ASS1 deficiency was detected in 98 of 214 patients (46%) of which 68 were randomized on the trial (44 ADI-PEG20+BSC and 24 BSC alone). 66 patients have progressed so far (42 ADI-PEG20+BSC vs. 24 BSC alone), and 32 patients were alive (23 ADI-PEG20+BSC vs. 9 BSC alone). The hazard ratio for PFS was 0.53 (95%, CI 0.31 to 0.90, p=0.02) with a median PFS of 98 days for patients randomized to ADI-PEG20+BSC compared with 59 days for patients receiving BSC alone. ADI-PEG20 toxicity in patients with MPM has been consistent with previous trials of ADI-PEG20 in melanoma and liver cancer: commonly skin injection site reactions (grade 1-2), infrequent episodes of neutropenia (range: grade 1-4), anaphylactoid reactions (2 patients with grade 3 episodes) and serum sickness (1 patient). The best response by modified RECIST was stable disease. Metabolic responses (in 39 evaluable ADI-treated patients) were as follows: 46% with partial response (18/39), 31% with stable disease (12/39), 15% progressive metabolic disease (6/39) and 8% mixed metabolic response (3/39) by FDG-PET assessment. There was a significant difference between IHC assessed ASS1-negative and ASS1-positive patients and the methylation status of the ASS1 gene (p=0.025).

      Conclusion
      ADI-PEG20 is generally well tolerated and shows evidence of clinically significant activity in patients selected for arginine-dependent MPM demonstrating differential methylation of ASS1. Arginine deprivation may have a role in the future management of MPM either alone or in combination with selected therapies.

      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.