Lung Cancer Therapies Get Personalized

Personalized medicine involves using information about a patient�s genotype or gene expression profile to tailor medical treatment to the individual. Oncology is not quite there yet, but researchers have started to lay the groundwork.

Personalized medicine involves using information about a patient’s

or

genotype

gene expression

profile to tailor medical treatment to the individual. Oncology is not quite there yet, but researchers have started to lay the groundwork. Some of this progress has transpired in developing lung cancer therapies.

“We are going in the direction of a more personalized therapy and moving away from the mindset that all lung cancers are created equal, which is not the case,” said Renato Martins, MD, medical director for the lung cancer group at the Seattle Cancer Care Alliance and an associate professor at University of Washington Department of Medicine, Division of Oncology.

Joan Schiller, MD, deputy director of Simmons Comprehensive Cancer Center and division director of Hematology/Oncology at the University of Texas-Southwestern Medical Center in Dallas echoed this, explaining that oncologists “basically give everybody [with lung cancer] the same treatment,” but changes are in the wind.

Targeted Therapies

Data from a recent study indicate that a 4-drug regimen of the chemotherapy agents carboplatin and paclitaxel (Taxol) combined with bevacizumab (Avastin) and cetuximab (Erbitux), 2 targeted therapies, was safe and increased survival in patients with advanced lung cancer. The 4-drug combination increased overall survival an average of 2 months. Dr. Schiller described the value contributed by the targeted agents: “The difference between chemotherapy and targeted agents is that chemotherapy kills cells pretty indiscriminately—both cancer cells as well as normal cells…Targeted therapies target the cancer cell very specifically.” She said that while targeted therapies have some effect on normal tissue, it is far less than the effects of chemotherapy.

Illustrating how personalized medicine works, Dr. Schiller explained that if you had 7 drugs exist to treat lung cancer and 2 patients, a close look at each patient’s case might indicate that Patient A would benefit most from drugs 2 and 5, whereas Patient B would do better with drugs 3 and 4. “That means a doctor takes out the tumor, looks at it under the microscope or runs appropriate tests, and, based on what is found…determine[s] the best treatment,” she said. The benefits of doing so, according to Dr. Schiller, include improved survival outcomes and fewer patients receiving ineffective treatments.

Making Headway

Journal of Clinical Oncology

Dr. Martins described some of the progress toward personalized medicine in lung cancer treatment. He said that oncologists have known for a while that 10% of patients with lung cancer have an epidermal growth factor receptor (EGFR) mutation, which leads to significantly increased sensitivity to manipulation of that pathway. Now, however, they can identify cells in the patient’s bloodstream that have that mutation. Referring to the results of an article in the May issue of , Dr. Martins said data indicate that administering erlotinib (Tarceva) as a first-line therapy in a genotype-directed fashion to patients with advanced non-small cell lung cancer who have EGFR mutations produces favorable clinical outcomes and tolerability.

“Conventional chemotherapy for patients with metastatic lung cancer has a response rate between 30% and 40%,” Dr. Martins said. “Patients with the EGFR mutation, when treated with [targeted agents] have a much higher response rate—between 55% and 90%.” In addition, when patients with the EGFR mutation were treated with EGFR-targeting agents, the median time to progression ranged between 10 and 12 months. This is comparable to the historical survival period of patients with non-small cell lung cancer. “Hopefully, we’re going to get to the point where we might not even need a biopsy,” Dr. Martin said. “You have a blood draw, and it will be able to not only establish diagnosis, but also to give molecular clues as to what kind of therapy the patient needs,” he added.

Weighing Costs/Benefits

As oncologists learn more about cancers, they are realizing that not all non-small cell lung cancers behave in an identical fashion. Going forward, it will be increasingly important to determine what differentiates one person’s lung cancer from another person’s and how those features play into selecting the drug or combination of drugs that will be more effective. Lin-Chi Chen, MD, a medical oncologist at Nevada Cancer Institute, cautions that it will also be important to weigh the benefit a patient is likely to receive from a drug against the drug’s adverse effects profile.

Dr. Chen questioned how long-term therapy, for example, might affect a patient’s quality of life. “If it takes a physical toll on their bodies that is unacceptable, then that’s going to be something that will be a moving target as we learn more about what some of these drugs do and how we can possibly treat some of those side effects,” she said. “The last thing that anybody involved in oncology wants is to make somebody feel sicker when they have marginal gain,” she added.

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