Lung cancer drug response tied to tumor type: study

LOS ANGELES (Reuters) – Testing lung cancer patients for tumor markers would enable doctors to choose which drug the patient is most likely to respond to, improving the chances for successful treatment, according to results from a recent trial.

The mid-stage study, conducted at the University of Texas M.D. Anderson Cancer Center in Houston and funded by the U.S. Army, enrolled 255 patients with advanced lung cancer who had previously been treated with chemotherapy.

“We are still in the dark ages with how we treat lung cancer patients,” said Dr. Edwin Kim, associate professor at the center’s thoracic/head and neck oncology department and the study’s lead investigator. Currently, they are separated only into “histologic” categories such as small cell or non-small cell lung cancer, with subtypes like squamous or non-squamous.

“As far as molecular testing nothing is standardly done in lung cancer at this time,” Kim said.

For other types of cancer — such as breast and colon — such testing has become common in recent years amid the development of biologic drugs designed to work only against tumors with specific genetic or molecular characteristics.

Patients in the MD Anderson trial had their lung tumors biopsied and tested for several “biomarkers” including epidermal growth factor receptor, or EGFR; vascular endothelial growth factor, or VEGF; a gene known as KRAS; and another that encodes for a protein called Cyclin D1.

Erlotinib, sold by Roche Holding AG and OSI Pharmaceuticals Inc under the brand name Tarceva, is designed to block EGFR, a protein found in high amounts on many types of cancer cells….

Tarceva is cleared for treating lung cancer that has gotten worse following at least one chemo regimen and the companies’ are seeking approval for its use in patients whose disease has remained stable after chemotherapy.

The M.D. Anderson trial also looked at treatment with AstraZeneca PLC’s Zactima, or vandetanib, which has targets including VEGF, a protein tumors need to grow vessels to supply blood. AstraZeneca last year pulled its regulatory applications for Zactima in lung cancer after an updated analysis found no overall survival advantage when the drug was added to chemotherapy.

Other drugs in the study were Nexavar, or sorafenib, sold by Onyx Pharmaceuticals Inc and Bayer AG, for treatment of kidney and liver cancers, and bexarotene, sold under the brand name Targretin as a treatment for a type of lymphoma.

The trial’s end point was disease control at eight weeks, which is seen as an indicator of overall survival. “In our study, if you made it to eight weeks, survival was 11.5 months. if not, it was 7.5 months,” Kim said, noting that as patients were enrolled they were directed to regimens which proved successful for earlier patients with similar tumor types.

The study found that 61 percent of patients with a KRAS mutation in their tumors who took Nexavar had no tumor growth at eight weeks, compared with 32 percent for the other three drugs.

Tarceva did best against EGFR mutations, Zactima for high VEGF expression and the Tarceva-Targretin fared best with Cyclin D1 defects or amplified numbers of the EGFR gene, the researchers said.

Overall, 46 percent of patients on the trial had disease control at 8 weeks, compared with a historical experience of around 30 percent for late-stage lung cancer patients.

Researchers said toxicities from the four drugs were minimal, with 6.5 percent of patients having a significant side effect.

Kim said future trials are needed to test combinations of therapies as well as single agents, including trials in earlier-stage lung cancer patients.

Roche is conducting a late-stage trial looking at the effectiveness of Tarceva as a first-line treatment for lung cancer patients with EGFR mutations.

Results were to be presented in Washington on Sunday at a meeting of the American Association for Cancer Research.

(Reporting by Deena Beasley; editing by Carol Bishopric)