Alectinib was at first approved for patients who have progressed on or are intolerant of crizotinib
, a drug for ALK-positive NSCLC widely approved (e.g. in USA by the FDA
). On October 12, 2017, the European Committee for Medicinal Products for Human Use (CHMP) recommended a change to the terms of the marketing authorisation by extending the indication of alectinib as monotherapy for the first-line treatment of adult patients with anaplastic lymphoma kinase (ALK)-positive advanced non-small cell lung cancer (NSCLC)
. The FDA approved it as first-line treatment for ALK-positive NSCLC in November 2017
Complete information about alectinib dosage and administration can be found here 
The standard dosage is:
Consult your treating doctor for personalised dosing.
- 600 mg (4 150 mg capsules) orally twice daily.
- Administer alectinib with food.
What is alectinib and how does it work?
Alectinib is a first-line oral therapeutic for advanced (metastatic) ALK-positive non-small cell lung cancer (NSCLC) 
The ALK (anaplastic lymphoma kinase) gene plays an important role in the development of the brain, and exerts its effects on specific neurons in the nervous system 
. Mutations of the ALK gene can occur in several different types of cells, including lung cells, and can result in the development of a tumour 
. ALK gene mutations occur in 3 to 7 % of patients with NSCLC 
Patients who have advanced ALK-positive NSCLC are generally highly responsive to ALK inhibitor crizotinib 
. However, almost all patients treated with crizotinib experience progression of their disease, developing secondary ALK mutations that are resistant to this therapeutic. Approximately 40 % of the ALK-positive NSCLC patients develop metastases in their central nervous system (brain and spinal cord), as an initial site of progression 
Similarly to crizotinib, alectinib is an ALK-inhibitor, which acts by inhibiting the activity of the ALK protein, and may thus prevent ALK-positive NSCLC-cells from growing and spreading 
. Crizotinib and alectinib target different mutations of the ALK-gene 
; the latter may thus prove effective when the former starts failing. Alectinib’s inhibiting action was indeed observed in ALK gene mutations resistant to crizotinib 
. Furthermore, while crizotinib is blocked by the brain’s defensive barrier 
, alectinib demonstrated its ability to penetrate the CNS and its shrinking effect on brain metastases 
. Recent studies have shown that alectinib extended the average time that people lived without their disease worsening compared to crizotinib 
What is alectinib’s approval status?
Alectinib was approved by
- PMDA (Japan) in July 2014 
- FDA (USA) on December 11, 2015 
- EMA (EU) on February 21, 2017 
- TGA (AUS) on March 14, 2017 
for ALK (anaplastic lymphoma kinase)-positive non-small cell lung cancer (NSCLC) in patients whose disease had worsened after—or who could not tolerate—treatment with crizotinib 
. In November 2017 the FDA extended its approval to the use as first-line treatment for ALK-positive NSCLC 
On October 12, 2017, the European Committee for Medicinal Products for Human Use (CHMP) recommended a change to the terms of the marketing authorisation by extending the indication of alectinib as monotherapy for the first-line treatment of adult patients with anaplastic lymphoma kinase (ALK)-positive advanced non-small cell lung cancer (NSCLC) 
The FDA approval on previously untreated ALK-positive NSCLC was based on a study (ALEX 
) which involved 303 patients who had not been previously treated for metastatic disease, and compared alectinib with crizotinib. It resulted that alectinib reduced the risk of death by 53 % compared to crizotinib when given as initial treatment (first-line) for ALK+ NSCLC 
. The median progression-free survival (PFS) was 25.7 months (95% CI: 19.9, not reached) in patients treated with alectinib versus 10.4 months (95% CI: 7.7, 14.6) for people treated with crizotinib 
. Complete response was achieved in 13 % of patients treated with alectinib vs. 6 % of those treated with crizotinib. After 18 months 37 % of patients in the alectinib's cohort were still in response, compared with 14 % of those in the crizotinib's cohort. The objective response rate on brain metastases was 81 % (38 % complete response) in the group treated with alectinib and 50 % (5 % complete response) in the group treated with crizotinib 
The PMDA approval was partly based on a study which included 46 patients and demonstrated a response rate of 93.5 % (95 % CI: 82.1 - 98.6 %) with a progression free survival at 12 months in 83 % (95 % CI: 68 - 92 %) of the patients 
The FDA, EMA, and TGA approvals for previously treated ALK-positive NSCLC were based on two studies (NP28673 and NP28761) that returned positive results 
. In the first study, which included 87 participants, 38 % (95 % CI: 28, 49) of participants experienced a partial shrinkage of their NSCLC tumours—an effect that lasted for an average of 7.5 months (95 % CI: 4.9, non-estimable) 
. The median progression-free survival (PFS) for people who received alectinib was 8.9 months 
. In the second study, which included 138 participants, 44 % of participants experienced a partial shrinkage of their NSCLC tumours, lasting for an average of 11.2 months. The trials also examined alectinib’s effect on individuals’ brain metastases, a common occurrence in this population. About 60 % of participants in the two trials who had measurable brain metastases experienced a complete or partial reduction in their brain tumours, lasting an average of 9.1 months 
Among the most common adverse reactions, both in first and second line treatment, were fatigue, constipation, oedema and myalgia (muscle pain)