Combining MEK and PI3K Inhibitors Appears Encouraging in a Safety Study with Early Signs of Anti-tumor Activity
Combination therapy targets MEK and PI3K pathways.
Phase I trials of single agent MEK and PI3K pathway inhibitors alone have shown signs of anti-tumor activity.
Abstract to be presented at AACR press conference.
ORLANDO, Fla. - The combination of two compounds that inhibit two of the most frequently mutated cancer pathways is showing promise in an ongoing Phase I trial, according to data presented at the AACR 102nd Annual Meeting 2011, held here April 2-6.
The research, presented by Johanna Bendell, M.D., tests a combination of GDC-0973, which inhibits MEK1/2 and GDC-0941, which inhibits PI3K. Bendell, director of Gastrointestinal Oncology Research and associate director of the drug development unit at the Sarah Cannon Research Institute in Nashville, said the RAS/RAF/MEK and PI3K pathways are altered in most tumors.
"Combining agents that block multiple pathways in tumor cells is likely the future of targeted therapy in cancer medicine. Blocking two pathways that interact with each other has the potential to have more anti-cancer activity than blocking either pathway alone," says Bendell.
The researchers enrolled 27 patients who received the combination of different doses of GDC-0973 and GDC-0941 on a daily 21 day on/7 day off schedule. The most common side effects seen were diarrhea, fatigue, rash, nausea, vomiting, decreased appetite and taste changes. Most of these side effects were mild.
Several patients have demonstrated decreases in tumor size, including two patients with melanoma, one with prostate cancer, two with non-small cell lung cancer. One patient with lung cancer and two patients with melanoma had stable disease over six months. The study is ongoing.
"We are very encouraged by this early data. We are able to give these agents together safely and we are seeing early signs of anti-cancer activity," said Bendell.
This abstract was presented at an AACR press conference on Saturday, April 2 at 10:00 a.m. ET in room W313 of the Orange County Convention Center.
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The mission of the American Association for Cancer Research is to prevent and cure cancer. Founded in 1907, the AACR is the worlds oldest and largest professional organization dedicated to advancing cancer research. The membership includes 33,000 basic, translational and clinical researchers; health care professionals; and cancer survivors and advocates in the United States and more than 90 other countries. The AACR marshals the full spectrum of expertise from the cancer community to accelerate progress in the prevention, diagnosis and treatment of cancer through high-quality scientific and educational programs. It funds innovative, meritorious research grants, research fellowships and career development awards. The AACR Annual Meeting attracts more than 18,000 participants who share the latest discoveries and developments in the field. Special conferences throughout the year present novel data across a wide variety of topics in cancer research, treatment and patient care. Including Cancer Discovery, the AACR publishes seven major peer-reviewed journals: Cancer Research; Clinical Cancer Research; Molecular Cancer Therapeutics; Molecular Cancer Research; Cancer Epidemiology, Biomarkers & Prevention; and Cancer Prevention Research. AACR journals represented 20 percent of the market share of total citations in 2009. The AACR also publishes CR, a magazine for cancer survivors and their families, patient advocates, physicians and scientists.
In Orlando, April 2-6: