Combination of Two Targeted Cancer Drugs Appears Safe in Early Testing | NCI Cancer Bulletin for April 5, 2011 - National Cancer Institute

Combination of Two Targeted Cancer Drugs Appears Safe in Early Testing

A small study testing a combination of two targeted drugs, each directed against a different pathway that is activated in cancer, has yielded positive results, researchers said at the AACR annual meeting. There were also some early indications that the combination treatment may have antitumor effects. The regimen was generally well tolerated, according to the researchers, and side effects were similar to those observed when the drugs were tested as single agents.

The combination therapy targets the RAS/RAF/MEK and PI3K pathways, which are among the most commonly mutated in cancer. Both drugs in the combination are made by Genentech; GDC-0973 inhibits the MEK pathway, and GDC-0941 targets the PI3K pathway.

“These pathways are altered in most tumors,” said Dr. Johanna Bendell of the Sarah Cannon Research Institute in Nashville, who presented the findings. The researchers were testing the idea that combining the drugs would have synergistic effects, but they were concerned that the combination would be too toxic for patients, she noted.

In the current study, at least, this was not the case. The most common side effects included diarrhea, fatigue, rash, nausea, and vomiting. Most of these were mild, according to the researchers.

Of the 27 patients enrolled in the trial, tumor size decreased in five patients, including two patients with melanoma, one with prostate cancer, and two with non-small cell lung cancer. One patient with lung cancer and two patients with melanoma had stable disease over 6 months, the researchers said.

The study is ongoing, and the researchers will continue to study the optimal dose and monitor antitumor activity.

“Many people believe that if you hit multiple pathways [in cancer] you will have better results, and this is a pioneering effort,” said Dr. Daniel Von Hoff of the Translational Genomics Research Institute, who moderated a press briefing on the study.

Dr. Bendell predicted that other companies will begin testing combinations of these targeted therapies. She acknowledged that testing two drugs that are produced by different companies can present additional challenges.

NCI Cancer Bulletin for April 5, 2011 - National Cancer Institute