Personalized Treatment for Lung Cancer Increased Survival

Oncogenic drivers in lung cancer tumors used to select patient chemotherapy

(RxWiki News) What if cancer chemotherapy could be customized for each patient's tumor? This individualized treatment may become a reality, as researchers test tumors for their genes and choose medications that work best based on those genes.

Gene changes involved in cancer development are called oncogenic drivers. Recently, a research team compared the presence of oncogenic genes in lung cancer tumors with chemotherapy given to patients.

The researchers found that more than half the lung cancer tumors had genes that could be paired with chemotherapy that specifically targeted that gene.

When chemotherapy was given based on oncogenic drivers in the tumors, patients lived longer.

"Discuss tumor gene testing with your oncologist."

The lead author of this published research was Mark G. Kris, MD, from Memorial Sloan Kettering Cancer Center in New York City.

The main goals of the study were to determine how many people had oncogenic drivers in their lung cancer tumors, whether tumors had more than one oncogenic driver, and whether treatment based on which oncogenic driver(s) were present affected the patients’ survival.

Patients with stage IV or recurrent adenocarcinoma of the lung were enrolled in the study. Adenocarcinoma is the most common form of lung cancer and is a type of lung cancer that does not originate in the small cells of the lung.

Over half the patients were former smokers and a third had never smoked.

Gene testing was done on lung tumor materials collected when lung biopsies were performed. The research team collected medical and treatment information on the study participants at least once a year.

Of all the patients enrolled in the study, 1,007 had at least one gene in their tumor studied, and the tumors of 733 patients were tested for 10 oncogenic drivers.

Of the 733 tumors specimens, 466 had one oncogenic driver and 24 had two oncogenic drivers.

The researchers frequently found three gene mutations among the lung tumor samples. Mutations or changes in a cell's genes have been associated with certain cancers, especially lung adenocarcinoma.

Medications that specifically target gene mutations have been developed as cancer treatments. The research team found gene mutations for which specifically gene-targeted chemotherapy existed in 64 percent of the tumors.

KRAS mutations were found in 25 percent of the tumor specimens, EGRF mutations were found in 17 percent, and rearrangements in the ALK gene was found in 8 percent of the samples.

The results of the tumor gene testing were used to choose a treatment targeted to the oncogenic drivers found. In all, 28 percent of the patients received cancer treatment that targeted their oncogenic drivers.

With the help of their doctors, the patients with two oncogenic drivers chose which gene to target for therapy. Ten patients were treated with erlotinib (brand name Tarceva) for their EGRF mutation and three patients received crizotinib (brand name Xalkori) for their ALK rearrangements.

Patients with oncogenic drivers who received targeted treatment lived longer than patients who did not have an oncogenic driver or those who did not receive targeted treatment.

The median (midpoint) survival of the 260 patients with an oncogenic driver who were treated with a targeted therapy was 3.5 years.

In the 318 patients who had an oncogenic driver, but who did not receive targeted therapy, median survival was 2.4 years. In the 360 patients where no oncogenic driver was found, the median survival was 2.1 years.

The median survival of the 49 patients who were found to have oncogenic drivers other than EGFR or ALK and who were treated with targeted therapy for those drivers was 4.9 years.

“Chemotherapy is no longer a standard but a default if patients do not have actionable drivers [drugs targeting their oncogenic drivers],” they said.

Boris Pasche, MD, PhD, from Wake Forest University in Winston Salem, North Carolina, and Stefan C. Grant, MD, JD, MBA, from the University of Alabama in Birmingham, wrote an accompanying editorial on this study

“Although much remains to be done, the incorporation of genomic medicine [the study of genes] into the study and treatment of lung cancer represents, at the very least, the end of the beginning for the care of these and other patients with cancer,” the authors of the editorial predicted.

This research and the accompanying editorial were published May 20 in JAMA.

Funding for the study was provided by the National Cancer Institute.

Several authors disclosed conflicts of interest. One of the authors, Bruce E. Johnson, MD, reported holding a patent for the EGFR mutation testing and receiving royalties from Dana-Farber Cancer Institute for EGFR mutation testing.

John Iafrate, MD, reported receiving royalties from Bioreference Labs for SnaPshot (gene) testing.

Samuel L. Aronson disclosed that his institute, Partners HealthCare, licensed the GeneInsight software that was used in partnership with Illumina for the testing in this study.

William Pao, MD, PhD, reported receiving fees and royalties from EGCR testing licensed in part to him.

Review Date: 
May 18, 2014