Xalkori (crizotinib) - 2 indications

Scroll down for more information on each indication:

• for the treatment of ALK+ non-small cell lung cancer; approved August of 2011
• for pediatric patients 1 year of age and older and young adults with ALK+ relapsed or refractory, systemic anaplastic large cell lymphoma; approved January 2021

General Information

Xalkori (crizotinib) is an oral selective, ATP-competitive small molecule dual inhibitor of mesenchymal epithelial transition growth factor (c-Met or hepatocyte growth factor) and ALK tyrosine kinases, both of which are indicated in cancer.

Xalkori is specifically approved for the following:

• locally advanced or metastatic non-small cell lung cancer (NSCLC) that is anaplastic lymphoma kinase (ALK)-positive as detected by an FDA-approved test;
• pediatric patients 1 year of age and older and young adults with relapsed or refractory, systemic ALK+ anaplastic large cell lymphoma (ALCL)

Xalkori is supplied as a tablet for oral administration. Capsules should be swallowed whole, with or without food. If a dose of Xalkori is missed, it should be taken as soon as the patient remembers unless it is less than six hours until the next dose. In this case the missed dose should not be taken. Two doses should not be taken at the same time to make up for a missed dose.

Mechanism of Action

Xalkori (crizotinib) is an inhibitor of receptor tyrosine kinases including ALK, Hepatocyte Growth Factor Receptor (HGFR, c-Met), and Recepteur d’Origine Nantais (RON). Translocations can affect the ALK gene resulting in the expression of oncogenic fusion proteins. The formation of ALK fusion proteins results in activation and dysregulation of the gene’s expression and signaling which can contribute to increased cell proliferation and survival in tumors expressing these proteins.

Side Effects

Adverse events associated with the use of Xalkori for NSCLC may include, but are not limited to, the following:

• vision disorders
• nausea
• diarrhea
• vomiting
• edema
• constipation
• elevated transaminases
• fatigue
• decreased appetite
• upper respiratory infection
• dizziness
• neuropathy

Adverse events associated with the use of Xalkori for ALCL may include, but are not limited to, the following:

• diarrhea
• vomiting
• nausea
• vision disorder
• headache
• musculoskeletal pain
• stomatitis
• fatigue
• decreased appetite
• pyrexia
• abdominal pain
• cough
• pruritus
• Grade 3–4 laboratory abnormalities including neutropenia, lymphopenia, and thrombocytopenia

Indication 1 - for the treatment of ALK+ non-small cell lung cancer

approved August of 2011

Dosage/Administration

The recommended dosage is 250 mg orally twice daily.

Clinical Results

The FDA approval of Xalkori for ALK+ NSCLC was based on two multi-center, single-arm studies (Studies A and B). Subjects enrolled into these studies had received prior systemic therapy, with the exception of 15 subjects in Study B who had no prior systemic treatment for locally advanced or metastatic disease. In both studies Xalkori was administered at 250 mg orally twice daily.
Study A
Data are from 136 subjects with locally advanced or metastatic ALK-positive NSCLC. The median duration of treatment was 22 weeks. There was one complete and 67 partial responses for an objective response rate of 50%. Seventy-nine percent of objective tumor responses were achieved during the first eight weeks of treatment. The median response duration was 41.9 weeks.
Study B
Data are from 119 subjects with locally advanced or metastatic ALK-positive NSCLC. The median duration of treatment was 32 weeks. There were two complete and 69 partial responses for an objective response rate of 61%. Fifty-five percent of objective tumor responses were achieved during the first eight weeks of treatment. The median response duration was 48.1 weeks.

Indication 2 - for pediatric patients 1 year of age and older and young adults with ALK+ relapsed or refractory, systemic anaplastic large cell lymphoma

approved January 2021

Dosage/Administration

The recommended dosage is 280 mg/m2 orally twice daily based on body surface area.

Clinical Trial Results

The FDA approval of Xalkori for ALK+ ALCL was based on results from Study ADVL0912, a multicenter, single arm, open-label study in 121 patients between the ages of 1 and 21 that included 26 patients with relapsed or refractory, systemic ALK-positive ALCL after at least one systemic treatment. Treatment with Xalkori resulted in an objective response rate of 88%. Among the 23 patients who achieved a response, 39% maintained their response for at least 6 months and 22% maintained their response for at least 12 months.