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| Pronunciation | /əˈlɛktɪnɪb/ə-LEK-ti-nib |
| Trade names | Alecensa |
| Other names | alectinib hydrochloride (JANJP) |
| AHFS/Drugs.com | Monograph |
| MedlinePlus | a616007 |
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| Routes of administration | By mouth |
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| Pharmacokinetic data | |
| Bioavailability | 37% (under fed conditions) |
| Protein binding | >99% |
| Metabolism | MainlyCYP3A4 |
| Metabolites | M4 (active) |
| Eliminationhalf-life | 33 hours (alectinib), 31 hours (M4) |
| Excretion | Feces (98%)[6] |
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| CompTox Dashboard(EPA) | |
| ECHA InfoCard | 100.256.083 |
| Chemical and physical data | |
| Formula | C30H34N4O2 |
| Molar mass | 482.628 g·mol−1 |
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Alectinib (INN[8]), sold under the brand nameAlecensa, is ananticancer medication that is used to treatnon-small-cell lung cancer (NSCLC).[6][7] It blocks the activity ofanaplastic lymphoma kinase (ALK).[9][10] It is takenby mouth.[6] It was developed byChugai Pharmaceutical Co. Japan, which is part of theHoffmann-La Roche group.
The most common side effects include constipation, muscle pain and edema (swelling) including of the ankles and feet, the face, the eyelids and the area around the eyes.[7]
Alectinib was approved for medical use in Japan in 2014, the United States in 2015, Canada in 2016, Australia in 2017, the European Union in 2017, and the United Kingdom in 2021.[6][7]
In the European Union, alectinib isindicated for the first-line treatment of adults with anaplastic lymphoma kinase (ALK)-positive advanced non-small cell lung cancer (NSCLC);[7] and for the treatment of adults with ALK‑positive advanced NSCLC previously treated withcrizotinib.[7]
In the United States, it is indicated for the treatment of people with anaplastic lymphoma kinase (ALK)-positive metastatic non-small cell lung cancer (NSCLC) as detected by an FDA-approved test.[6] In April 2024, the USFood and Drug Administration (FDA) expanded the indication of alectinib to include adjuvant treatment following tumor resection in people with anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer (NSCLC), as detected by an FDA-approved test.[11]
There are no reportedcontraindications.[6][12]
Apart from unspecificgastrointestinal effects such asconstipation (in 34% of patients) andnausea (22%), common adverse effects in studies includedoedema (swelling; 34%),myalgia (muscle pain; 31%),anaemia (low red blood cell count), sight disorders, light sensitivity andrashes (all below 20%).[13] Serious side effects occurred in 19% of patients; fatal ones in 2.8%.[6]
Alectinib has a low potential for interactions. While it is metabolised by the liver enzymeCYP3A4, and blockers of this enzyme accordingly increase its concentrations in the body, they alsodecrease concentrations of theactive metabolite M4, resulting in only a small overall effect. Conversely, CYP3A4inducers decrease alectinib concentrations and increase M4 concentrations. Interactions via otherCYP enzymes andtransporter proteins cannot be excluded but are unlikely to be of clinical significance.[13][12]
The substance potently and selectively blocks tworeceptor tyrosine kinase enzymes:anaplastic lymphoma kinase (ALK) and theRET proto-oncogene. The active metabolite M4 has similar activity against ALK. Inhibition of ALK subsequently blocks cell signalling pathways, includingSTAT3 and thePI3K/AKT/mTOR pathway, and induces death (apoptosis) of tumour cells.[13][12]
When taken with a meal, the absolutebioavailability of the drug is 37%, and highestblood plasma concentrations are reached after four to six hours. Steady state conditions are reached within seven days.Plasma protein binding of alectinib and M4 is over 99%. The enzyme mainly responsible for alectinib metabolism is CYP3A4; other CYP enzymes andaldehyde dehydrogenases only play a small role. Alectinib and M4 account for 76% of the circulating substance, while the rest are minor metabolites.[13][14]
Plasma half-life of alectinib is 32.5 hours, and that of M4 is 30.7 hours. 98% are excreted via the faeces, of which 84% are unchanged alectinib and 6% are M4. Less than 1% are found in the urine.[13][14]
Alectinib has apKa of 7.05. It is used in form of thehydrochloride, which is a white to yellow-white lumpy powder.[6]
The approvals were based mainly on two trials: In a Japanese Phase I–II trial, after approximately 2 years, 19.6% of patients had achieved a complete response, and the 2-yearprogression-free survival rate was 76%.[10] In February 2016 the J-ALEX phase III study comparing alectinib with crizotinib was terminated early because an interim analysis showed thatprogression-free survival was longer with alectinib.[15]
In November 2017, the FDA approved alectinib for thefirst-line treatment of people with ALK-positive metastatic non-small cell lung cancer.[16] This based on the phase 3 ALEX trial comparing it with crizotinib.[16]
Efficacy was demonstrated in a global, randomized, open-label trial (ALINA, NCT03456076) in participants with ALK-positive NSCLC who had complete tumor resection.[11] Eligible participants were required to have resectable stage IB (tumors ≥ 4 cm) to IIIA NSCLC (by AJCC 7th edition) with ALK rearrangements identified by a locally performed FDA-approved ALK test or by a centrally performed VENTANA ALK (D5F3) CDx assay.[11] A total of 257 participants were randomized (1:1) to receive alectinib 600 mg orally twice daily or platinum-based chemotherapy following tumor resection.[11] The application was grantedpriority review andorphan drug designations.[11]
In April 2024, the FDA approved alectinib as an adjuvant treatment for people with ALK-positive early-stage lung cancer.[17] This was based on the Phase III ALINA study [NCT03456076].[18]
In April 2024, theCommittee for Medicinal Products for Human Use of theEuropean Medicines Agency adopted a positive opinion for the use of alectinib for adjuvant treatment of resected non‑small cell lung cancer (NSCLC).[7][19] In June 2024, the EU approved alectinib as an adjuvant treatment for people in the EU with ALK-positive early-stage lung cancer.[20] This was based on the Phase III ALINA study [NCT03456076].[21]
In October 2024, the UK`s NICE recommended alectinib as an adjuvant treatment for adults for the treatment of stage 1B to 3A ALK-positive non-small-cell lung cancer.[22]
Alectinib was approved in Japan in July 2014,[23] for the treatment ofALK fusion-gene positive, unresectable, advanced or recurrent non-small-cell lung cancer (NSCLC).[10]
Alectinib was granted anaccelerated approval by the USFood and Drug Administration (FDA) in December 2015, to treat people with advanced ALK-positive NSCLC whose disease worsened after, or who could not tolerate, treatment with crizotinib (Xalkori).[9]
It received conditional approval by theEuropean Medicines Agency in February 2017, for the same indication.[24] The approval was upgraded from conditional to full approval in December 2017.[25]
This article incorporates text from this source, which is in thepublic domain.