Experimental Drugs Show Promise Against EGFR-mutated Lung Cancers

Researchers are making progress against advanced non-small cell lung cancers that have mutations in the EGFR gene. These mutations cause the cancer cells to have too much of the EGFR protein, which leads them to grow faster. These mutations are more common in women and in people who have never smoked.

In the past decade, the FDA has approved several drugs called EGFR inhibitors, which block the signal from the EGFR protein that tells cells to grow. These targeted therapies, including erlotinib (Tarceva) and afatinib (Gilotrif), tend to work better than chemotherapy for EGFR-mutated lung cancers, often shrinking tumors for several months. But eventually these drugs stop working for most people, usually because the cells develop another mutation in the EGFR gene.

Two studies in the April 30, 2015 issue of the New England Journal of Medicine show that 2 new EGFR inhibitors both show promise for people whose lung cancers are no longer responding to other EGFR inhibitors because of a new genetic mutation.

In one study, researchers testing the drug rociletinib found that 59% of participants’ lung tumors shrank while they were taking it. In the other study, 61% of participants’ lung tumors shrank while they were taking a drug called – for now – AZD9291. Like other EGFR inhibitors, these experimental drugs eventually stopped working for most people. But taking the drugs gave most participants at least 6 more months of good quality of life without their cancer getting worse, and often longer.

Lecia V. Sequist, MD, MPH, principle investigator of the rociletinib trial, said the drug made a significant difference in the lives of people who took it. “An additional year of cancer control can mean the birth of a grandchild or the ability to attend weddings and graduations,” said Sequist in a statement. “I witnessed patients being able to go on amazing trips with their families – to run, bike, row, swim, and literally to climb mountains – because their disease was under control and their symptoms were improved. For many patients this drug was truly a miracle in their lives.”

The drugs had manageable side effects for most people, including diarrhea, nausea, and rash with both drugs, and high blood sugar with rociletinib.

The US Food and Drug Administration is reviewing the drugs under an accelerated approval process designed to get promising therapies on the market faster. These would be the first targeted therapies for patients whose tumors stop responding to EGFR inhibitors. In the meantime, researchers are studying whether there are more effective ways to use the drugs, for example, in combination with other treatments or if given before treatment with older EGFR inhibitors instead of after they stopped working.

The American Cancer Society medical and editorial content team
Our team is made up of doctors and master’s-prepared nurses with deep knowledge of cancer care as well as journalists, editors, and translators with extensive experience in medical writing.

AZD9291 in EGFR Inhibitor–Resistant Non–Small-Cell Lung Cancer. Published in the April 30, 2015 issue of the New England Journal of Medicine. First author Pasi A. Jänne, MD, PhD, Dana–Farber Cancer Institute, Boston.

Rociletinib in EGFR-Mutated Non–Small-Cell Lung Cancer. Published in the April 30, 2015 issue of the New England Journal of Medicine. First author Lecia V. Sequist, MD, MPH, Massachusetts General Hospital, Boston.


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