Long-term effects of crizotinib in ALK-positive tumors (excluding NSCLC): A phase 1b open-label study
Journal
American Journal of Hematology
Journal Volume
93
Journal Issue
5
Pages
607-614
Date Issued
2018
Author(s)
Gambacorti-Passerini C.
Orlov S.
Zhang L.
Braiteh F.
Huang H.
Esaki T.
Horibe K.
Ahn J.-S.
Beck J.T.
Edenfield W.J.
Shi Y.
Taylor M.
Tamura K.
Van Tine B.A.
Paolini J.
Selaru P.
Kim T.M.
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. ? 2018 The Authors American Journal of Hematology Published by Wiley Periodicals, Inc.
SDGs
Other Subjects
anaplastic lymphoma kinase; creatine kinase; crizotinib; anaplastic lymphoma kinase; crizotinib; abdominal pain; adolescent; adult; advanced cancer; aged; anaplastic large cell lymphoma; Article; brain infarction; cancer survival; clinical article; colon carcinoma; constipation; controlled study; creatine kinase blood level; deep vein thrombosis; diarrhea; disease severity; drug effect; drug response; drug safety; edema; fatigue; female; headache; heart failure; heart muscle ischemia; human; interstitial lung disease; leukopenia; lymphoma; male; middle aged; multicenter study; multiple cycle treatment; National Cancer Institute International Response Criteria; nausea; neutropenia; phase 1 clinical trial; plasma cell granuloma; priority journal; progression free survival; response evaluation criteria in solid tumors; side effect; thyroid medullary carcinoma; treatment duration; visual disorder; vomiting; young adult; antagonists and inhibitors; clinical trial; complication; genetics; lung tumor; mutation; neoplasm; non small cell lung cancer; treatment outcome; Adolescent; Adult; Aged; Anaplastic Lymphoma Kinase; Carcinoma, Non-Small-Cell Lung; Crizotinib; Female; Humans; Lung Neoplasms; Male; Middle Aged; Mutation; Neoplasms; Treatment Outcome; Young Adult
Publisher
Wiley-Liss Inc.
Type
journal article