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Crizotinib was the first ALK inhibitor, approved four years after ALK fusions were found in lung cancer; it was also the first drug for ROS1 lung cancer and for ALK-positive lymphoma and inflammatory myofibroblastic tumour in children.
PROFILE 1007/1014 established it over chemotherapy in ALK+ NSCLC (2011 accelerated, 2013 full); ROS1 approval 2016 (PROFILE 1001, 72% response). Superseded first line by alectinib, brigatinib and lorlatinib (poor CNS penetration). Paediatric approvals for ALK+ ALCL (2021) and IMT (2022). Visual disturbance, oedema, hepatotoxicity.
ATP-competitive inhibitor of ALK, ROS1 and MET kinases. Connects to ALK, ROS1 and MET.
1.Crizotinib slips into a pocket on ALK.
Oral, self-administered, so it is a Part D drug: covered through a stand-alone Part D plan or Medicare Advantage drug benefit, usually on the specialty tier with 25 to 33% coinsurance until the annual cap ($2,000 in 2025, $2,100 in 2026).
Covered for FDA-labelled and NCCN-listed uses, but almost always behind prior authorisation confirming diagnosis, biomarker and line of therapy; dispensed through a specialty pharmacy.
Part D out-of-pocket capped at $2,000 (2025) / $2,100 (2026). Medicare patients cannot use manufacturer co-pay cards; charity funds (PAN, HealthWell, CancerCare) and the Extra Help subsidy are the routes.
Sources: Medicare.gov: Drug coverage (Part D) · Medicare.gov: Costs for Medicare drug coverage (annual out-of-pocket cap). Not medical or financial advice; verify with your plan.
Sources: NICE TA406 · SMC advice: crizotinib. Funding decisions are indication-specific and change monthly; verify with NICE and your treating team.
Locally advanced or metastatic NSCLC that is ALK-positive as detected by an FDA-approved test
Accelerated approval on a surrogate endpoint, with a confirmatory trial required.
Locally advanced or metastatic NSCLC that is ALK-positive as detected by an FDA-approved test
Confirmed: the accelerated approval of 2011 converted to traditional approval 2.2 years after it was granted.
| Region | Year | Indication |
|---|---|---|
| US | 2011 | ALK-positive metastatic NSCLC |
| US | 2016 | ROS1-positive metastatic NSCLC |
| US | 2021 | Relapsed ALK-positive ALCL in patients 1-21 years |
| US | 2022 | ALK-positive inflammatory myofibroblastic tumour |
| EU | 2012 | Conditional Oct 2012; full approval 2015 |
| England (NICE) | 2024 | ROS1-positive advanced non-small-cell lung cancer in patients who have not had a ROS1 inhibitor · TA1021, published 4 December 2024; NICE asks that the least expensive of crizotinib and entrectinib is used. |
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Cabozantinib is the preferred first-line targeted therapy for metastatic papillary renal cell carcinoma; immunotherapy combinations are being tested on top of it.
The current first choice for ALK-positive lung cancer in most guidelines, and the strongest evidence in solid tumour oncology that a drug can be designed to work inside the brain. Five-year follow-up has since shown the majority of patients still progression-free.
It turned the laboratory prediction into a clinical rule: after a second-generation ALK inhibitor, genotype the tumour, and treat the absence of an ALK mutation as evidence that the cancer has stopped depending on ALK.
First-line ALK treatment moved to a drug designed for the brain, and brain metastasis prevention became an explicit design goal rather than a hoped-for side effect. ALK-positive lung cancer is now among the longest-surviving metastatic solid tumours.
ALK is the reason young, KRAS wild-type patients should have fusion testing even though the overall rate is one in six hundred.
It made MET exon 14 a clinical entity rather than a sequencing curiosity, and identified the patients most likely to be missed: older people whose age would otherwise argue against broad sequencing.
It made repeat biopsy and genotyping at progression the standard in ALK-positive lung cancer, because after a second-generation inhibitor the presence or absence of an ALK mutation is what separates patients who should receive a third-generation inhibitor from those who should not.
It is the cleanest demonstration in oncology that resistance is a property of a particular drug bound to a particular protein rather than a property of the tumour, and that genotyping at every progression can reopen an option that looked closed.
Query for this drug: (TITLE:"Crizotinib" OR ABSTRACT:"Crizotinib" OR TITLE:"Xalkori" OR ABSTRACT:"Xalkori") AND (cancer OR tumor OR tumour OR oncology OR carcinoma OR lymphoma OR leukemia OR leukaemia OR myeloma OR sarcoma OR melanoma OR glioma). Results are unfiltered search hits about Crizotinib, not a curated reading list.
Shares Identification of targetable ALK rearrangements in pancreatic ductal adenocarcinoma, ALESIA, J-ALEX, Study to Investigate Outcome of Individualized Treatment in Patients With Metastatic Colorectal Cancer.
Shares Crizotinib in ROS1-rearranged non-small-cell lung cancer, ROS1 rearrangements define a unique molecular class of lung cancers, Resensitization to crizotinib by the lorlatinib ALK resistance mutation L1198F, ALK resistance mutations and efficacy of lorlatinib in advanced anaplastic lymphoma kinase-positive non-small-cell lung cancer.
Shares A Study to Compare the Efficacy and Safety of Entrectinib and Crizotinib in Participants With Advanced or Metastatic ROS1 Non-small Cell Lung Cancer (NSCLC) With and Without Central Nervous System (CNS) Metastases, PROFILE 1001 ROS1 expansion cohort, ROS1 fusion (ROS1-positive), University of Colorado Cancer Center.
Shares Resensitization to crizotinib by the lorlatinib ALK resistance mutation L1198F, University of Colorado Cancer Center, ALK resistance mutations and efficacy of lorlatinib in advanced anaplastic lymphoma kinase-positive non-small-cell lung cancer, Molecular mechanisms of resistance to first- and second-generation ALK inhibitors in ALK-rearranged lung cancer.
Shares ALESIA, J-ALEX, PROFILE 1001 ROS1 expansion cohort, ROS1 fusion (ROS1-positive).
Shares ALTA-1L, University of Colorado Cancer Center, ALEX, First-line lorlatinib or crizotinib in advanced ALK-positive lung cancer.
Shares Sarcomatoid carcinoma of the lung, MET exon 14 skipping mutation, Capmatinib, MET exon 14 mutations in non-small-cell lung cancer are associated with advanced age and stage-dependent MET genomic amplification and c-Met overexpression.
Shares A Study of Repotrectinib Versus Crizotinib in Participants With Locally Advanced or Metastatic Tyrosine Kinase Inhibitor (TKI)-naïve ROS1-positive Non-Small Cell Lung Cancer (NSCLC) (TRIDENT-3), PROFILE 1001 ROS1 expansion cohort, ROS1 fusion (ROS1-positive), Inflammatory myofibroblastic tumour (IMT).