FDA approves game-changing immunotherapy drug to fight lung cancer

In an unprecedented study conducted at UCLA and 29 other sites worldwide, Keytruda (pembrolizumab) was found to be effective in the treatment of patients with advanced non-small cell lung cancer

• U.S. Food and Drug Administration has approved the groundbreaking immunotherapy drug Keytruda (pembrolizumab) to treat advanced non-small cell lung cancer (NSCLC)
• Three-year international study led by UCLA showed responses which were generally of long duration with the drug in patients with NSCLC
• Results also found the drug to be generally better tolerated than typical chemotherapies
• The study identified which patients were most likely to benefit by evaluating characteristics of patients’ tumors, leading to simultaneous approval of a test to select patients most likely to benefit from the drug

The U.S. Food and Drug Administration today approved the breakthrough drug Keytruda to treat advanced non-small cell lung cancer, signaling a paradigm shift in the way the deadliest of all cancers is treated.

In the largest study published to date using immunotherapy to treat lung cancer, the drug Keytruda (pembrolizumab) was tested on approximately 500 patients with non-small cell lung cancer. Because so many of the patients in the study showed significant long-lasting responses, in October 2014 the FDA granted the drug “breakthrough therapy” status for use in lung cancer, allowing it to be fast-tracked for approval.

“The approval of this drug and a test to identify patients most likely to benefit has the potential to transform the way that lung cancer is treated,” said Dr. Edward Garon, the study’s principal investigator and a researcher at UCLA’s Jonsson Comprehensive Cancer Center. “The quality and duration of disease response that was seen in the trial had previously been extremely rare in lung cancer. For people battling this deadly disease, this approach provides real hope of long-lasting responses while avoiding the toxicities of typical chemotherapy.”

The response rate and duration of response for Keytruda were much greater than for drugs traditionally used to treat lung cancer. In the three-year clinical trial, the overall response rate (the percentage of people in whom tumors were substantially reduced in size) was 19 percent. In people who responded to treatment, the average duration of response exceeded one year, a remarkable advance in this difficult disease.

Keytruda, a drug that has already been proven to extend the lives of people with advanced melanoma, is an antibody that targets the protein PD-1, which is expressed by immune cells. When it binds to the another protein called PD-L1, PD-1 acts as an immune checkpoint, dampening the immune system’s T cells which otherwise could attack cancer cells, said Garon, who also is an associate professor of hematology-oncology at the David Geffen School of Medicine at UCLA.

Some tumors are able to evade an immune response by expressing high levels of PD-L1. So by blocking the interaction between PD-1 and PD-L1, Keytruda in effect enables the patient’s immune system to attack the cancer.

Since PD-L1 binding to PD-1 prevents the T cells from attacking cells, it was thought that higher levels of PD-L1 in tumors could correlate with favorable clinical outcomes with PD-1 inhibitor treatment. Approximately a quarter of screened patients in the trial had PD-L1 expression in at least half of their tumor cells. Among these patients, the overall response rate was nearly 50 percent. The study was the first to validate that clinical outcomes with this class of drug was directly associated with the level of PD-L1 expression.

Judith Gasson, director of the Jonsson Cancer Center and senior associate dean for research at the David Geffen School of Medicine at UCLA, said researchers have long hoped to develop an effective and lasting immunotherapy to fight cancer.

“We have long believed that harnessing the power of our own immune systems would dramatically alter cancer treatment,” she said. “Based upon the pioneering work conducted at UCLA, we are beginning to see the clinical benefits of this research in the most challenging cancers.”

Lung cancer is the leading cause of cancer deaths worldwide; the American Lung Association estimates more than 158,000 people in the U.S. will die from the disease this year alone. Non-small cell lung cancer accounts for approximately 85 percent of all lung cancers.

Further research into its use in other types of cancer is ongoing, as are efforts to combine Keytruda with other drugs to increase the percentage of patients who could benefit from immunotherapy.

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