Are Two Cancer Drugs Better Than One?

Non small cell lung cancer with KRAS mutations chemotherapy adding selumetinib may improve survival

(RxWiki News) Recent trends in cancer research have focused on combination therapies, where drugs that supplement each other's weaknesses show greater results in fighting cancer than either would alone.

A lot of great research has been showcased during the annual meeting of the American Society of Clinical Oncology this week.

In terms of lung cancer, one of the most impressive presentations was made by Pasi A. Jänne, MD/PhD, the scientific co-director of Dana-Farber’s Belfer Institute for Applied Cancer Science.

Dr. Jänne presented the findings from his phase II study comparing randomized treatment of adding selumetinib to docetaxel chemotherapy.

"Ask your oncologist about combination therapy."

The study involved 87 non-small cell lung cancer (NSCLC) patients whose tumors carry a mutation in the gene KRAS. Such tumors account for about 20 percent of NSCLC cases, but no targeted therapy has proved effective against them in previous clinical research.

The drug under investigation, selumetinib, doesn’t attack KRAS directly, but interferes with one of its molecular henchmen, a protein called MEK.

The patients enrolled in the study had advanced cases of non small cell lung cancer. The study was a comparison of standard chemotherapy with docetaxel against a combination of docetaxel with selumetinib.

Results with selumetinib were shown to be significantly better than placebo, with patients responding to the chemotherapy's effects 37 percent faster when given selumetinib.

Survival without any growth of the cancer was more than doubled, with patients given both drugs having an average of 5.3 months before cancer growth in comparison to 2.1 months with docetaxel chemotherapy alone.

Overall survival with selumetinib was 9.4 months in comparison to 5.2 months with docetaxel chemotherapy alone, but more patients would need to be enrolled in the trial before the results can be considered statistically significant.

Selumetinib targets the MEK gene, and as previous research has shown, by blocking MEK selumetinib is able to shut down the BRAF molecular pathway.

So far, the BRAF gene has been identified as a key mutation in cancers of the thyroid, colon, ovary, and skin. Researchers also documented the interference of MEK with KRAS, another gene commonly involved in cancer development.

“This clinical trial demonstrates that a combination of chemotherapy and selumetinib is significantly better than chemotherapy alone for this group of patients – better in terms of tumor response to therapy and in terms of survival times prior to advance of the disease,” stated Dr. Jänne.

“It suggests that for the first time we may have an effective treatment for KRAS-mutant lung cancer, which is the largest single subtype of the disease. These impressive clinical findings not only have implications for the treatment of lung cancer but all cancers that harbor KRAS mutations, including pancreatic and colorectal cancer.”

Side effects from the drug trial included lowered levels of immune cells, fatigue, acne, and respiratory problems.

Study results presented at conferences are considered preliminary until published in a peer-reviewed journal.

Several researchers involved in the study disclosed financial ties to AstraZeneca, who funded the study.

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Review Date: 
June 7, 2012