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

• Published in: American journal of hematology Vol. 93; no. 5; pp. 607 - 614
• Main Authors: 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
• Format: Journal Article
• Language: English
• Published: United States Wiley Subscription Services, Inc 01.05.2018; John Wiley and Sons Inc
• Subjects: Adolescent; Adult; Aged; Anaplastic large-cell lymphoma; Anaplastic Lymphoma Kinase - antagonists & inhibitors; Anaplastic Lymphoma Kinase - genetics; Cancer; Carcinoma, Non-Small-Cell Lung - complications; Carcinoma, Non-Small-Cell Lung - drug therapy; Colon; Crizotinib - adverse effects; Crizotinib - pharmacology; Diarrhea; Enzyme inhibitors; Female; Hematology; Humans; Inflammation; Long-term effects; Lung cancer; Lung Neoplasms; Lymphoma; Male; Middle Aged; Mutation; Neoplasms - complications; Neoplasms - drug therapy; Non-small cell lung carcinoma; Patients; Protein-tyrosine kinase; Safety; Solid tumors; Targeted cancer therapy; Thyroid cancer; Treatment Outcome; Tumors; Young Adult
• ISSN: 0361-8609; 1096-8652
• DOI: 10.1002/ajh.25043

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.