Author of

• 17629

  +

  P2.03b - Poster Session with Presenters Present (ID 465)

  • Event: WCLC 2016
  • Type: Poster Presenters Present
  • Track: Advanced NSCLC
  • Presentations: 1
  • Moderators:
  • Coordinates: 12/06/2016, 14:30 - 15:45, Hall B (Poster Area)

  • 17641

    +

    P2.03b-012 - A Phase II Study of Etirinotecan Pegol (NKTR-102) in Patients with Refractory Brain Metastases and Advanced Lung Cancer (ID 4345)

    14:30 - 14:30  |  Author(s): A. Holmes Tisch
    • Abstract

    Background:
    Up to 40% of lung cancer patients develop brain metastases. As brain metastases often progress following radiotherapy, chemotherapeutics with central nervous system (CNS) activity are needed. Etirinotecan pegol (NKTR-102) is a PEG-conjugate prodrug of irinotecan, resulting in a half-life of 37 days and accumulation in tumors with permeable vasculature. This phase II trial evaluated the CNS activity of etirinotecan pegol in patients with lung cancer and refractory brain metastases.
    
    Methods:
    Patients with lung cancer and brain metastases were eligible who had received prior systemic therapy and prior brain-directed neurosurgery, radiation/radiosurgery, or refused whole brain radiotherapy (WBRT). Measurable brain metastases were defined as one >= 10 mm; or one 5-9 mm with others >= 3 mm, totaling >= 10 mm. Etirinotecan pegol was administered at 145 mg/m2 IV every 3 weeks. Response (modified RECIST 1.1) was assessed with brain MRI and systemic CT every 6 weeks. The primary endpoint was a 25% or greater 12-week CNS disease control rate (CNS-DCR; defined as unconfirmed response or stable disease with systemic non-progression) in a non-small cell lung cancer (NSCLC) cohort. Another exploratory cohort enrolled small cell lung cancer (SCLC) patients.
    
    Results:
    In the NSCLC cohort, twelve patients were enrolled, all with adenocarcinoma. Genomic alterations included six (50%) with EGFR mutation, and one each with HER2, KRAS, ROS1, and NRAS. Patients received a median of 2.5 prior systemic treatments. Two (17%) patients had prior neurosurgery, ten patients (83%) had irradiation - 3 WBRT, 9 radiosurgery. Common related toxicities were nausea and diarrhea (each in 50%), vomiting (22%) and blurred vision (22%). One patient died after developing diarrhea and dehydration. CNS responses lasting 24, 8, and 6 weeks were observed in 25% (3/12) - all EGFR mutation positive. The 6-week CNS-DCR was 50% (6/12), but 12-week CNS-DCR was 17% (2/12). Median progression-free survival was 11.4 weeks (95% CI 5.3-11.7) and median overall survival from study entry was 29.6 weeks (95% CI 22.3-38.2). In the SCLC cohort, two patients were enrolled. One patient with prior PCI had CNS response at 5 weeks but died of neutropenic infection; one who refused prior WBRT had CNS progression at 6 weeks.
    
    Conclusion:
    Radiographic responses of brain metastases were observed in patients following administration of etirinotecan pegol, but the study did not meet the primary endpoint because the 12-week CNS-DCR was 17%. Further study of etirinotecan pegol is ongoing in patients with breast cancer and brain metastases.