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Alectinib

A second generation small molecule inhibitor of the ALK protein providing a useful treatment option for patients who have progressed on crizotinib because of its ability to target crizotinib resistant mutant forms of the ALK protein.

Trade name Alecensa.

Presently the front line standard of care for patients with ALK positive non-small cell lung cancer.

This drug out performed crizotinib a the phase III Alex trial for NSCLC.

Used in the setting of acquiring resistance to crizotinib for adenocarcinoma of the lung EML4-ALK positive.

In the ALEX trial, a randomized phase 3 study, compared alectinib with crizotinib in treatment-naïve patients with NSCLC harboring ALK rearrangements: The 12-month event-free survival was 68.4% versus 48.7% for alectinib and crizotinib, respectively.

In the ALEX trial in treatment naïve patients is demonstrated superior CNS activity compared with crizotinib: the CNS overall response rate was 81% and 50%, respectively in the CNS duration of response were 17.3 and 5.5 months, respectively.

Overall five-year survival rate was 62.5% with alectinib  and 45.5% with crizotinib in ALEX study.

In patients with acquired resistance to crizotinib there is a 55-69% response rate.

CNS response rate in patients with measurable disease in crizotinib pretreated patients is 54%.

Has a higher response rate than crizotinib in patients with brain metastases.

Overall better tolerated than crizotinib.

Has a pronounced benefit in survival impatience with AL K rearrangement positive non-small cell lung cancer and poor performance status.

Common AEs of all grades include fatigue (41%), constipation (34%), edema (30%), and myalgia (29%).

It can cause anemia, lymphopenia, hepatic toxicity, increased creatine phosphokinase, hyperglycemia, electrolyte abnormalities, and increased creatinine, periodic monitoring of these laboratory values is important, although most of these abnormalities are grade 1 or 2.

Median progression free survival significantly longer with this drug than crizotinib in TKI naive patients.

Dose 600 mg orally twice dAILY.

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