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|Promising Data for KRAS Mutant Advanced NSCLC Patients Presented at ASCO|
This study showed statistically significant improvement in progression-free survival, objective response rate, and alive and progression-free at six months as well as a trend for improvement in overall survival in favor of selumetinib in combination with docetaxel versus docetaxel alone.
The tolerability profile of selumetinib in combination with docetaxel was consistent with previously conducted studies. There was an increased incidence of Grade 3 or 4 neutropenia and febrile neutropenia and of Grade 1 or 2 diarrhea in patients receiving the selumetinib combination versus docetaxel alone.
Overall survival was longer for selumetinib in combination with docetaxel compared to docetaxel alone (9.4 mo vs 5.2 mo; 56 events, median follow-up 219 days) but did not reach statistical significance. Hazards were non-proportional (HR 0.80; 80% CI 0.56, 1.14; 1-sided p=0.2069). All secondary endpoints, including response rate (selumetinib/docetaxel 37%, docetaxel 0%; p<0.0001) and progression free survival (selumetinib/docetaxel 5.3 mo, docetaxel 2.1 mo; 71 events; HR = 0.58; 80% CI 0.42, 0.79; 1-sided p=0.0138), were significantly improved for selumetinib in combination with docetaxel versus docetaxel alone.
“In the U.S., KRAS is the most prevalent oncogenic alteration in NSCLC
with approximately 20 percent of patients harboring a KRAS mutation,”
said Pasi A. Jänne, M.D., Ph.D., Primary Investigator and Associate
Professor of Medicine,
This study is the first completed randomized combination trial with a mitogen-activated protein kinase (MEK) inhibitor in KRAS mutant advanced NSCLC and we believe is the first prospective study to demonstrate clinical benefit as defined by response rate and progression-free survival of a targeted therapy for patients with KRAS mutant cancer of any type. Targeting MEK dependent tumors with selumetinib demonstrates the potential of a personalized approach to medicine in the treatment of cancer and suggests that further clinical evaluation of selumetinib in KRAS mutation positive NSCLC patients is warranted.
About KRAS Non-Small Cell Lung Cancer
Approximately 20 to 25 percent of the NSCLC patient population has the KRAS mutation which amounts to approximately 160,000 patients globally. Currently, patients with KRAS NSCLC have a poor prognosis with limited treatment options. In a prior study, docetaxel in second and third-line treatment for KRAS positive NSCLC showed a progression free survival of 1.5 months and overall survival of 4.2 months.
About MEK and selumetinib
MEK is a key protein kinase in the RAS/RAF/MEK/ERK pathway, which
signals cancer cell proliferation and survival. MEK has been shown to be
frequently activated in cancer, in particular in tumors that have
mutations, including BRAF and NRAS, in the RAS and RAF
pathways. Selumetinib is an anti-cancer drug in Phase II development in
a range of tumors. It is a small molecule MEK inhibitor that targets a
key position in this pathway. Selumetinib was invented by
About lung cancer
Over 1.35 million new cases of lung cancer are diagnosed every year and nearly 1.2 million people die as a result of this devastating disease - more than breast, colon and prostate cancer combined. If lung cancer is detected at early stages, before it has spread to other organs or lymph nodes, around half of patients can survive for five years or more. However, few lung cancers are found at this early stage and it is normally diagnosed at the advanced stage, when five year survival falls to approximately 15 percent.
This press release contains forward-looking statements within the
meaning of the Private Securities Litigation Reform Act of 1995,
including statements about the timing of completion or initiation of
further trials involving selumetinib, the potential for the results of
ongoing clinical trials to support regulatory approval or the marketing
success of selumetinib, and future plans to progress and develop
selumetinib. These statements involve significant risks and
uncertainties, including those discussed in the most recent annual
report filed on Form 10-K, quarterly reports filed on Form 10-Q, and
other reports filed by Array with the
Array BioPharma Inc.