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

Carlo Gambacorti-Passerini, Sergey Orlov, Li Zhang, Fadi Braiteh, Huiqiang Huang, Taito Esaki, Keizo Horibe, Jin Seok Ahn, Joseph T. Beck, William Jeffrey Edenfield, Yuankai Shi, Matthew Taylor, Kenji Tamura, Brian A. Van Tine, Shang Ju Wu, Jolanda Paolini, Paulina Selaru, Tae Min Kim

    Research output: Contribution to journalArticle

    13 Citations (Scopus)

    Abstract

    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, ALK 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, n=18; IMT, n=9; other tumors, n=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.

    Original languageEnglish (US)
    JournalAmerican Journal of Hematology
    DOIs
    StateAccepted/In press - Jan 1 2018

    Fingerprint

    Non-Small Cell Lung Carcinoma
    Neoplasms
    Lymphoma
    Confidence Intervals
    Safety
    Anaplastic Large-Cell Lymphoma
    crizotinib
    anaplastic lymphoma kinase
    National Cancer Institute (U.S.)
    Vision Disorders
    Therapeutics
    Disease-Free Survival
    Diarrhea
    Colon
    Carcinoma

    ASJC Scopus subject areas

    • Hematology

    Cite this

    Gambacorti-Passerini, C., Orlov, S., Zhang, L., Braiteh, F., Huang, H., Esaki, T., ... Kim, T. M. (Accepted/In press). Long-term effects of crizotinib in ALK-positive tumors (excluding NSCLC): A phase 1b open-label study. American Journal of Hematology. https://doi.org/10.1002/ajh.25043

    Long-term effects of crizotinib in ALK-positive tumors (excluding NSCLC) : A phase 1b open-label study. / Gambacorti-Passerini, Carlo; Orlov, Sergey; Zhang, Li; Braiteh, Fadi; Huang, Huiqiang; Esaki, Taito; Horibe, Keizo; Ahn, Jin Seok; Beck, Joseph T.; Edenfield, William Jeffrey; Shi, Yuankai; Taylor, Matthew; Tamura, Kenji; Van Tine, Brian A.; Wu, Shang Ju; Paolini, Jolanda; Selaru, Paulina; Kim, Tae Min.

    In: American Journal of Hematology, 01.01.2018.

    Research output: Contribution to journalArticle

    Gambacorti-Passerini, C, Orlov, S, Zhang, L, Braiteh, F, Huang, H, Esaki, T, Horibe, K, Ahn, JS, Beck, JT, Edenfield, WJ, Shi, Y, Taylor, M, Tamura, K, Van Tine, BA, Wu, SJ, Paolini, J, Selaru, P & Kim, TM 2018, 'Long-term effects of crizotinib in ALK-positive tumors (excluding NSCLC): A phase 1b open-label study', American Journal of Hematology. https://doi.org/10.1002/ajh.25043
    Gambacorti-Passerini, Carlo ; Orlov, Sergey ; Zhang, Li ; Braiteh, Fadi ; Huang, Huiqiang ; Esaki, Taito ; Horibe, Keizo ; Ahn, Jin Seok ; Beck, Joseph T. ; Edenfield, William Jeffrey ; Shi, Yuankai ; Taylor, Matthew ; Tamura, Kenji ; Van Tine, Brian A. ; Wu, Shang Ju ; Paolini, Jolanda ; Selaru, Paulina ; Kim, Tae Min. / Long-term effects of crizotinib in ALK-positive tumors (excluding NSCLC) : A phase 1b open-label study. In: American Journal of Hematology. 2018.
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    abstract = "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, ALK 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, n=18; IMT, n=9; other tumors, n=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.",
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    AU - Orlov, Sergey

    AU - Zhang, Li

    AU - Braiteh, Fadi

    AU - Huang, Huiqiang

    AU - Esaki, Taito

    AU - Horibe, Keizo

    AU - Ahn, Jin Seok

    AU - Beck, Joseph T.

    AU - Edenfield, William Jeffrey

    AU - Shi, Yuankai

    AU - Taylor, Matthew

    AU - Tamura, Kenji

    AU - Van Tine, Brian A.

    AU - Wu, Shang Ju

    AU - Paolini, Jolanda

    AU - Selaru, Paulina

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