AstraZeneca has announced the results from a phase 3 trial of selumetinib, a MEK 1/2 inhibitor, in combination with docetaxel chemotherapy as second-line treatment in patients with KRAS mutation-positive (KRASm) locally advanced or metastatic non–small-cell lung cancer (NSCLC).
The study did not meet its primary endpoint of progression-free survival (PFS), and selumetinib did not have a significant effect on overall survival (OS).
MEK 1 and MEK 2 are critical components of the RAS–ERK pathway, the activation of which is implicated in driving cancer growth and progression, including in patients with KRASm NSCLC.
SELECT-1 was a double-blind, randomized, placebo-controlled trial designed to assess the efficacy and safety of selumetinib (75 mg twice daily, administered orally on a continuous schedule) in combination with docetaxel (75 mg/m2 intravenously on day 1 of every 21-day cycle) compared with matched placebo in combination with docetaxel (same schedule) in 510 patients receiving second-line treatment for KRASm locally advanced or metastatic NSCLC (stage IIIB–IV), confirmed by central testing of tumor tissue using the Cobas KRAS mutation test (Roche Molecular Systems).
In May 2016, the FDA granted an orphan drug designation to selumetinib for adjuvant treatment of patients with stage III or stage IV differentiated thyroid cancer. The medication is being explored in that setting, as well as in patients with neurofibromatosis type 1, a genetic disorder that causes tumors to grow along nerve tissue.
Source: AstraZeneca; August 9, 2016.