Targeted Cancer Therapy Casts Wider Net

Lung cancer therapy options directed at gene mutations expand

December 11, 2012 / Author:  / Reviewed by: Joseph V. Madia, MD

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(dailyRx News) Targeting cancer gene mutations has been changing the way non-small cell lung cancer (NSCLC) is treated. As scientists learn more about the genetic makeup of tumors, more personalized therapy has become available.

Investigators have found that genetic testing of tumors is possible as part of a doctor’s routine workflow, and new cell mutations are emerging that can be targets for drug treatment.

Surgery, radiation therapy and chemotherapy have been typical treatment options for NSCLC.

More recently, researchers have developed drugs that are designed to repair gene alterations that cause tumors to grow. Over 90 percent of cancers have some type of genetic alteration.

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Stephanie Cardarella, MD, medical oncologist at Dana-Farber/Brigham and Women’s Cancer Center and an instructor in medicine at Harvard Medical School in Boston, Massachusetts, led the study, which took 344 tumor specimens from 419 patients with NSCLC.

All the specimens were genotyped, which means scientists detailed the genetic structure of each tumor. This type of large-scale study helps doctors identify new cell mutations that spur cancer cell growth. The average turnaround time for genotyping a specimen was 31 days.

It is now standard practice for tumor specimens from NSCLC patients to be examined for EGFR mutations and ALK (anaplastic lymphoma kinase) rearrangements. EGFR means epidermal growth factor receptor. EGF is a protein found in the body and when it binds with the EGFR protein on the surface of cancer cells, it triggers a growth reaction and cells divide excessively. Drugs, such as gefitinib (Iressa) and erlotinib (Tarceva), stop this reaction.

ALK is an enzyme, and mutations, or rearrangements, of this enzyme trigger growth of certain NSCLC cells. ALK gene arrangements are most often found in cancer tumors that do not have the EGFR mutation. ALK inhibiting drugs, such as crizotinib (Xalkori), block a reaction that leads to tumor cell growth.

KRAS is another gene that may cause cancer when mutated. Agents, such as cetuximab (Erbitux), can block the growth of mutated KRAS genes and stop growth in certain tumors. Authors of this study say that routine cell analysis for KRAS has been ongoing since 2004.

Patients treated with “inhibitor” drugs can often live longer by anywhere from months to a few years. Typically, however, some cancer cells become resistant to the drugs and the disease eventually grows again. Research is ongoing to improve performance of these drugs.

Of the 344 specimens analyzed in this study, 185 (54 percent) had at least one identifiable gene alteration. In addition to finding tumors with EGFR and ALK, investigators developed genetic profiles of tumors with these genes: BRAF, HER2 and PIK3CA.

"The goals of the genomic characterization of our NSCLC patients are to help guide therapy and ultimately lead to improved outcomes for those patients with specific genomic changes,” the authors of this study said. "As the repertoire of mutations for which targeted therapy may be offered expands, strategies to enable rapid, accurate and comprehensive clinical genotyping will be essential.”

Mark G. Kris, MD, chief of the Thoracic Oncology Service and The William and Joy Ruane Chair in Thoracic Oncology at Memorial Sloan-Kettering Cancer Center in New York City, said in an interview with OncLive.com, the cost of genetic testing for the driver mutations is between $750 and $1,250.

The study is published in the December 2012 issue of the International Association for the Study of Lung Cancer's (IASLC) Journal of Thoracic Oncology.