Reference Detail

Ref Type

Journal Article

PMID

(29352732)

Authors

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

Title

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

Journal	Vol	Issue	Date	Pages	Journal Short Title
American journal of hematology	93	5	2018 05	607-614	Am J Hematol

URL

Abstract Text

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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Molecular Profile	Treatment Approach

Gene Name	Source	Synonyms	Protein Domains	Gene Description	Gene Role

Therapy Name	Drugs	Efficacy Evidence	Clinical Trials

Drug Name	Trade Name	Synonyms	Drug Classes	Drug Description

Gene	Variant	Impact	Protein Effect	Variant Description	Associated with drug Resistance

Molecular Profile	Indication/Tumor Type	Response Type	Therapy Name	Approval Status	Evidence Type	Efficacy Evidence	References
ALK rearrange	inflammatory myofibroblastic tumor	sensitive	Crizotinib	FDA approved	Actionable	In a Phase Ib trial (PROFILE 1013) that supported FDA approval, treatment with Xalkori (crizotinib) resulted in an objective response rate of 66.7% (6/9, 1 complete response, 5 partial responses) and stable disease in 33.3% (3/9) of adult patients with advanced ALK-positive inflammatory myofibroblastic tumors, with a median duration of response of 74.1 weeks in (PMID: 29352732; NCT00939770).	29352732 detail...
ALK rearrange	thyroid gland medullary carcinoma	predicted - sensitive	Crizotinib	Case Reports/Case Series	Actionable	In a Phase Ib trial (PROFILE 1013), Xalkori (crizotinib) therapy resulted in a partial response in a patient with medullary thyroid carcinoma harboring ALK rearrangement with a response duration of 16.1 weeks (PMID: 29352732; NCT00939770).	29352732
ALK fusion	inflammatory myofibroblastic tumor	sensitive	Crizotinib	FDA approved	Actionable	In a Phase Ib trial (PROFILE 1013) that supported FDA approval, treatment with Xalkori (crizotinib) resulted in an objective response rate of 66.7% (6/9, 1 complete response, 5 partial responses) and stable disease in 33.3% (3/9) of adult patients with advanced ALK-positive inflammatory myofibroblastic tumors, with a median duration of response of 74.1 weeks in (PMID: 29352732; NCT00939770).	29352732 detail...
ALK F1174L	neuroblastoma	conflicting	Crizotinib	Case Reports/Case Series	Actionable	In a Phase Ib trial (PROFILE 1013), Xalkori (crizotinib) therapy resulted in stable disease lasting 19 months in a patient with advanced neuroblastoma harboring ALK F1174L (PMID: 29352732; NCT00939770).	29352732
ALK rearrange	colon mucinous adenocarcinoma	predicted - sensitive	Crizotinib	Case Reports/Case Series	Actionable	In a Phase Ib trial (PROFILE 1013), Xalkori (crizotinib) therapy resulted in a partial response in a patient with colon mucinous carcinoma harboring ALK rearrangement with a response duration of 103.3 weeks (PMID: 29352732; NCT00939770).	29352732
ALK rearrange	lymphoma	predicted - sensitive	Crizotinib	Phase I	Actionable	In a Phase Ib trial (PROFILE 1013), Xalkori (crizotinib) treatment resulted in an objective response rate of 52.9% (9/17, 8 complete responses, 1 partial response) and stable disease in 17.6% (3/17) of patients with advanced ALK-positive lymphomas, with a median duration of response of 135.9 weeks in (PMID: 29352732; NCT00939770).	29352732