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M. Winter



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    MA16 - Novel Strategies in Targeted Therapy (ID 407)

    • Event: WCLC 2016
    • Type: Mini Oral Session
    • Track: Chemotherapy/Targeted Therapy/Immunotherapy
    • Presentations: 1
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      MA16.09 - Antitumor Activity and Safety of Crizotinib in Patients with MET Exon 14-Altered Advanced Non-Small Cell Lung Cancer (ID 5162)

      15:14 - 15:20  |  Author(s): M. Winter

      • Abstract
      • Presentation
      • Slides

      Background:
      MET alterations leading to exon 14 skipping occur in ~4% of non-squamous non‑small cell lung cancer (NSCLCs) and 20–30% of sarcomatoid lung carcinomas, resulting in MET activation and sensitivity to MET inhibitors in vitro.[1–4] Crizotinib, initially developed as a MET inhibitor, is currently approved for the treatment of ALK-rearranged and ROS1-rearranged advanced NSCLC. We present crizotinib antitumor activity and safety data in patients (pts) with MET exon 14-altered advanced NSCLC.

      Methods:
      Advanced NSCLC pts positive for MET exon 14-alteration status determined locally by molecular profiling were enrolled into an expansion cohort of the ongoing phase I PROFILE 1001 study (NCT00585195) and received crizotinib at a starting dose of 250 mg BID. Objective responses were assessed using RECIST v1.0.

      Results:
      As of the data cut-off of Feb 01, 2016, 21 pts with MET exon 14-altered NSCLC received crizotinib treatment (18 response-evaluable, 3 not yet evaluable). Median age was 68 y (range: 53−87). Tumor histology was: 76% adenocarcinoma, 14% sarcomatoid adenocarcinoma, 5% adenosquamous carcinoma, and 5% squamous cell carcinoma. Sixty-two percent (62%) of pts were former-smokers, 38% never-smokers, and there were no current smokers. Duration of treatment ranged from 0.2 to 12.2 mo, with 76% of pts (16/21) still ongoing. Five pts discontinued treatment (1 due to AE, 3 due to clinical or disease progression, and 1 preferred alternative treatment formulation). PRs were observed in 8 pts, for an objective response rate of 44% (95% CI: 22–69); 9 pts had stable disease. Median time to response was 7.8 weeks (range: 7.0–16.3), which was the approximate time of the scheduled first on treatment tumor scans for patients. Median progression-free survival could not be calculated. The most common (≥25%) treatment-related AEs (TRAEs) were edema (43%) diarrhea (33%), nausea (33%), vision disorder (33%), and vomiting (29%). Most TRAEs were grade 1/2 in severity and consistent with the known safety profile of crizotinib. Four grade 3 TRAEs (edema, bradycardia, anemia, and weight increased) and no grade 4 or 5 TRAEs were reported. Enrollment of pts with MET exon 14-altered NSCLC continues, and updated data will be available at the time of presentation.

      Conclusion:
      Crizotinib has clinically meaningful antitumor activity in pts with MET exon 14-altered advanced NSCLC. The drug has a tolerable AE profile, consistent with that previously reported for pts with ALK-rearranged or ROS1-rearranged advanced NSCLC. Further study of crizotinib in this pt population is warranted.

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