In clinical trial, immunotherapy better than chemo in advanced lung cancer

A new study has found immunotherapy to be more effective than chemotherapy in treating most previously treated patients with advanced lung cancer, and demonstrated effectiveness in a wider population of people than previously known to benefit from the therapy.

Over 1,000 people with PD-L1 expressing non-small cell lung cancer (NSCLC) were enrolled in this clinical trial comparing the immunotherapy drug pembrolizumab to the established standard chemotherapy drug docetaxel. The data confirmed that patients receiving the immunotherapy lived longer than those who received chemotherapy, said Dr. Edward Garon, the study’s senior author and a researcher at the UCLA Jonsson Comprehensive Cancer Center.

The immunotherapy was also definitively found for the first time to be effective in patients with low levels of PD-L1 in their tumors.

“This treatment provides real hope of long-lasting responses while avoiding the toxicities of typical chemotherapy in a broad population of lung cancer patients,” said Garon, who is an associate professor of hematology and oncology at the David Geffen School of Medicine. “We are excited that these results have identified a larger group of patients for whom in general, immunotherapy is a superior treatment option than  traditional approaches.”

The study will be published online in the journal The Lancet on December 19.

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

Pembrolizumab (marketed under the brand name Keytruda) is an antibody that targets the protein PD-1, which is expressed by immune cells. When it binds to PD-L1, PD-1 acts as an immune checkpoint, dampening the immune system’s T cells which otherwise could attack cancer cells. Some tumors are able to evade an immune response by expressing PD-L1. So, by blocking the interaction between PD-1 and PD-L1, pembrolizumab 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 had been thought that PD-L1 levels in tumors could correlate with favorable clinical outcomes with PD-1 inhibitor treatment. This hypothesis was validated in a study led by Garon and published earlier this year in the New England Journal of Medicine.

Approximately two thirds of patients enrolled in the clinical trial whose tumors could be tested were PD-L1-positive (meaning the patient had PD-L1 expressed in at least one percent of their tumor cells). Participants were randomly assigned to different treatment groups, with two groups receiving differing doses of immunotherapy, and a third group receiving the chemotherapy.

Results showed that patients receiving the immunotherapy were more likely to have their tumor shrink significantly, and more importantly, the patients receiving immunotherapy lived significantly longer than those who received chemotherapy. In addition, the rate of serious toxicity related to therapy (defined using common clinical trial criteria), was lower in patients receiving pembrolizumab.

“By continuing to refine and expand our selection of patients who stand to benefit from this type of therapy, we are profoundly changing the way that patients with this common cancer are treated,” said Garon. “For most patients, this now offers data showing that immunotherapy leads to superior clinical outcomes with a side effect profile that is generally favorable to our traditional therapies.”

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