Long‐term effects of crizotinib in ALK‐positive tumors (excluding NSCLC): A phase 1b open‐label study

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  • Carlo Gambacorti‐Passerini
    University of Milano Bicocca, San Gerardo Hospital Monza Italy
  • Sergey Orlov
    St Petersburg Medical University St Petersburg Russia
  • Li Zhang
    State Key Laboratory of Oncology in South China Collaborative Innovation Center for Cancer Medicine, Sun Yat‐Sen University Cancer Center Guangdong China
  • Fadi Braiteh
    Comprehensive Cancer Centers of Nevada Las Vegas Nevada
  • Huiqiang Huang
    Department of Medical Oncology Sun‐Yat Sen University Cancer Center Guangdong China
  • Taito Esaki
    National Kyushu Cancer Center Fukuoka Japan
  • Keizo Horibe
    National Hospital Organization Nagoya Medical Center Nagoya Japan
  • Jin‐Seok Ahn
    Samsung Medical Center, Sungkyunkwan University School of Medicine Seoul South Korea
  • Joseph T. Beck
    Highlands Oncology Group Fayetteville Arkansas
  • William Jeffrey Edenfield
    Cancer Institute of Greenville Health System Greenville South Carolina
  • Yuankai Shi
    Department of Medical Oncology, Beijing Key Laboratory of Clinical Study on Anticancer Molecular Targeted Drugs National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College Beijing China
  • Matthew Taylor
    Oregon Health & Science University Portland Oregon
  • Kenji Tamura
    National Cancer Center Hospital Tokyo Japan
  • Brian A. Van Tine
    Washington University School of Medicine St. Louis Missouri
  • Shang‐Ju Wu
    National Taiwan University Hospital Taipei Taiwan
  • Jolanda Paolini
    Pfizer Oncology Milan Italy
  • Paulina Selaru
    Pfizer Oncology La Jolla California
  • Tae Min Kim
    Seoul National University Hospital Seoul South Korea

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<jats:title>Abstract</jats:title><jats:p>Crizotinib, an inhibitor of anaplastic lymphoma kinase (ALK), MET, and ROS1, is approved for treatment of patients with ALK‐positive or ROS1‐positive advanced non‐small‐cell lung cancer (NSCLC). However, <jats:italic>ALK</jats:italic> rearrangements are also implicated in other malignancies, including anaplastic large‐cell lymphoma and inflammatory myofibroblastic tumors (IMTs). In this ongoing, multicenter, single‐arm, open‐label phase 1b study (PROFILE 1013; NCT01121588), patients with ALK‐positive advanced malignancies other than NSCLC were to receive a starting dose of crizotinib 250 mg twice daily. Primary endpoints were safety and objective responses based on Response Evaluation Criteria in Solid Tumors version 1.1 or National Cancer Institute International Response Criteria. Forty‐four patients were enrolled (lymphoma, <jats:italic>n</jats:italic> = 18; IMT, <jats:italic>n</jats:italic> = 9; other tumors, <jats:italic>n</jats:italic> = 17). The objective response rate was 53% (95% confidence interval [CI], 28–77) for lymphoma, with 8 complete responses (CRs) and 1 partial response (PR); 67% (95% CI, 30–93) for IMTs, with 1 CR and 5 PRs; and 12% (95% CI, 2–36) for other tumors, with 2 PRs in patients affected by colon carcinoma and medullary thyroid cancer, respectively. The median duration of treatment was almost 3 years for patients with lymphoma and IMTs, with 2‐year progression‐free survival of 63% and 67%, respectively. The most common treatment‐related adverse events were diarrhea (45.5%) and vision disorders (45.5%), mostly grade 1. These findings indicate strong and durable activity of crizotinib in ALK‐positive lymphomas and IMTs. The safety profile was consistent with the known safety profile of crizotinib even with long‐term treatment.</jats:p>

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