Pharmacological Class:
Kinase inhibitor.
Active Ingredient(s):
Osimertinib 40mg, 80mg; tablets.
Company
AstraZeneca Pharmaceuticals
Indication(s):
Treatment of patients with metastatic epidermal growth factor receptor (EGFR) T790M mutation-positive non-small cell lung cancer (NSCLC), as detected by an FDA-approved test, who have progressed on or after EGFR tyrosine kinase inhibitor therapy.
Pharmacology:
Osimertinib is a kinase inhibitor of the EGFR, which binds irreversibly to certain mutant forms of EGFR (T790M, L858R, and exon 19 deletion) at approximately 9-fold lower concentrations than wild-type. It exhibits anti-tumor activity against NSCLC lines harboring EGFR-mutations (T790M/L858R, L858R, T790M/exon 19 deletion, and exon 19 deletion) and, to a lesser extent, wild-type EGFR amplifications.
Clinical Trials:
The efficacy of Tagrisso was studied in 2 multicenter, single-arm, open-label clinical trials (Studies 1 and 2) of 411 patients with metastatic EGFR T790M mutation-positive NSCLC who had progressed on prior systemic therapy, including an EGFR TKI.
The major efficacy outcome measure for both studies was objective response rate (ORR) according to RECIST v1.1 as eva luated by a Blinded Independent Central Review. An additional outcome measure was duration of response.
The overall ORR was seen in 59% of patients (95% CI: 54, 64) with 0.5% exhibiting complete response and 59% exhibiting partial response. The majority of patients (96%) with confirmed objective responses had ongoing responses ranging from 1.1–5.6 months after a median duration of follow-up of 4.2 months (Study 1) and 4.0 months (Study 2).
For more clinical trial data, see full labeling.
Legal Classification:
Rx
Adults:
80mg once daily until disease progression or unacceptable toxicity. If swallowing difficulty, may disperse tab in 4tbsps (~50mL) of non-carbonated water only; stir and swallow immediately or give through NG tube; then rinse container with 4–8oz water and drink immediately or give through NG tube. Dose modification: see full labeling.
Children:
Not established.
Warnings/Precautions:
Confirm presence of T790M mutation prior to treatment initiation. Permanently discontinue if interstitial lung disease (ILD)/pneumonitis is confirmed; QTc interval prolongation with signs/symptoms of life-threatening arrhythmia; persistent, asymptomatic LV dysfunction that does not resolve within 4 weeks; symptomatic CHF; or if no improvement of Grade ≥3 adverse reaction within 3 weeks occurs. Withhold dose if worsening respiratory symptoms indicative of ILD occur or if QTc interval >500msec on ≥2 separate electrocardiograms (ECGs). Monitor ECGs and electrolytes periodically in patients with congenital long QTc syndrome, CHF, electrolyte abnormalities, or those who are taking drugs known to prolong the QTc interval. Assess LVEF by echocardiogram or multigated acquisition (MUGA) scan prior to initiation and every 3 months during treatment. Severe renal impairment (CrCl <30mL/min) or ESRD. Moderate or severe hepatic impairment. Pregnancy. Females of reproductive potential should use effective contraception during and for 6 weeks after final dose; males with female partners of reproductive potential should use effective contraception during and for 4 months after final dose. Nursing mothers: not recommended (during and for 2 weeks after final dose).
Interaction(s)
Avoid concomitant with strong CYP3A inhibitors (eg, telithromycin, itraconazole, ritonavir, nefazodone); if no other alternative, monitor closely. Avoid concomitant with strong CYP3A inducers (eg, phenytoin, rifampicin, carbamazepine, St. John’s Wort). Avoid concomitant with sensitive substrates of CYP3A, BCRP, or CYP1A2 with narrow therapeutic indices (eg, fentanyl, cyclosporine, quinidine, ergots, phenytoin, carbamazepine).
Adverse Reaction(s)
Diarrhea, rash, dry skin, nail toxicity.
How Supplied:
Tabs—30
LAST UPDATED:
4/1/2016
