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Am J Hematol. 2018 May;93(5):607-614. doi: 10.1002/ajh.25043. Epub 2018 Feb 8.

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

Author information

1
University of Milano Bicocca, San Gerardo Hospital, Monza, Italy.
2
St Petersburg Medical University, St Petersburg, Russia.
3
State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangdong, China.
4
Comprehensive Cancer Centers of Nevada, Las Vegas, Nevada.
5
Department of Medical Oncology, Sun-Yat Sen University Cancer Center, Guangdong, China.
6
National Kyushu Cancer Center, Fukuoka, Japan.
7
National Hospital Organization Nagoya Medical Center, Nagoya, Japan.
8
Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea.
9
Highlands Oncology Group, Fayetteville, Arkansas.
10
Cancer Institute of Greenville Health System, Greenville, South Carolina.
11
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.
12
Oregon Health & Science University, Portland, Oregon.
13
National Cancer Center Hospital, Tokyo, Japan.
14
Washington University School of Medicine, St. Louis, Missouri.
15
National Taiwan University Hospital, Taipei, Taiwan.
16
Pfizer Oncology, Milan, Italy.
17
Pfizer Oncology, La Jolla, California.
18
Seoul National University Hospital, Seoul, South Korea.

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.

PMID:
29352732
PMCID:
PMC5947833
DOI:
10.1002/ajh.25043
[Indexed for MEDLINE]
Free PMC Article

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