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AstraZeneca's Selumetinib Fails in Phase III Lung Cancer Trial

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AstraZeneca’s investigational drug candidate, selumetinib failed to show progression-free survival (PFS) in KRAS mutation-positive (KRASm) non-small cell lung cancer (NSCLC) patients.

AstraZeneca-logo-3DKRAS is the most common genetic mutations found in NSCLC patients.

NSCLC by histology

Figure 1. Non-small cell lung cancer by histology and mutations (photo credit: Transl Lung Cancer Res. 2015 Feb;4(1):36-54. doi: 10.3978/j.issn.2218-6751.2014.05.01).

Selumetinib-structure

Selumetinib is an oral, highly selective MEK 1/2 inhibitor which was given in combination with docetaxel chemotherapy to KRASm NSCLC patients as a second line treatment in the Phase III clinical study. MEK 1/2 are the essential components of the pathway whose activation leads to cancer growth and progression.

selumetinib MEK1 inhibitor

Figure 2. MAPK and PI3K/AKT pathways and mechanism of action of selumetinib (photo credit: Front Oncol. 2013 Mar 19;3:54. doi: 10.3389/fonc.2013.00054. eCollection 2013).

The phase III clinical trial randomized 510 patients who received either 75mg selumetinib oral, twice daily or placebo in combination with intravenously administered docetaxel.

The results demonstrated that selumetinib failed to meet the trial endpoint of progression free survival and also did not show any significant effect on overall survival (OS). The adverse events profile for selumetinib and docetaxel also remained same.

Selumetinib was discovered by Array BioPharma and later AstraZeneca acquired its exclusive worldwide rights from Array BioPharma by upfront and milestone payments of $26.5 million and will also give about $30 million as potential development milestone payments and royalties on product sales.

Earlier, selumetinib has also failed in another Phase III trial. It was done to evaluate whether the drug could prolong the survival of patients with melanoma that has reached eye.

Still, AstraZeneca can hope for some positive results from selumetinib in the forthcoming clinical trials being performed to evaluate its efficiency to treat differentiated thyroid cancer (DTC) patients and type 1 neurofibromatosis (NF1) patients. Few months back, selumetinib received Orphan Drug Designation from US Food and Drug Association (FDA) for adjuvant treatment of patients suffering from DTC.

Featured Image Credit: metro.co.uk

One comment

  1. great article Tiash Saha….i am a postgraduate in biochemistry really liked the way you have shown the effect of drug on cancer …hope the drug passes the clinical trial with positive result….

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