In a study led by UCLA investigators, treatment with the immunotherapy drug pembrolizumab helped more than 15 percent of people with advanced non-small cell lung cancer live for at least five years — and 25 percent of patients whose tumor cells had a specific protein lived at least that long. When the study began in 2012, the average five-year survival rate was just 5.5 percent for people with that type of cancer.
Immune-mediated adverse events at three years (September 6, 2016) and at five years (November 5, 2018) of follow-up. Immune-mediated adverse events were classified based on a list of preferred terms identified by the sponsor as having an immune etiology. Because there were changes in events included in this list between the three- and five-year analyses, certain events classified as immune-mediated at three years may not have been so-classified at five years.
Graphic: Courtesy of Dr. Edward Garon
The study, conducted by researchers at the UCLA Jonsson Comprehensive Cancer Center and more than 30 other centers, was the first to evaluate pembrolizumab as a treatment for lung cancer. “We can no longer look at this disease as one in which we should always be measuring survival in months,” says Edward Garon, MD (FEL ’06), associate professor of medicine and a member of the Jonsson Cancer Center. “These findings substantially alter the outlook for people with advanced non-small cell lung cancer. The fact that we have patients in this trial who are still alive, and thriving, seven years after starting pembrolizumab is quite remarkable.”
The study involved 550 participants, 101 of whom had not received any previous treatments for advanced cancer and 449 who had. All participants were given pembrolizumab every two-to-three weeks. In 2015, just three years into the study, the participants’ positive early responses to pembrolizumab prompted the Food and Drug Administration to approve the treatment for some people with non-small cell lung cancer. Since then, the drug has been approved for broader use, becoming a staple for managing the disease.
Pembrolizumab is an immune checkpoint inhibitor that works by blocking the interaction between PD-1 and PD-L1, which are both proteins on the surface of T cells. By blocking this interaction, which generally inhibits the body’s immune response, pembrolizumab activates the immune system to better attack the cancer. The researchers found that the drug worked better in people who had higher levels of PD-L1, regardless of whether they had been previously treated for cancer.
Among those who were previously untreated, 29.6 percent of those with PD-L1 expression in at least half of their tumor cells were alive after five years, versus 15.7 percent of those with low PD-L1 expression. For people who had received prior cancer treatment, 25 percent who had PD-L1 expression in at least half of their tumor cells were alive after five years, while 12.6 percent of those with low PD-L1 levels and 3.5 percent with no PD-L1 expression lived that long.
According to the National Cancer Institute, lung cancer is the leading cause of cancer deaths in the U.S. and worldwide. Only about one-third of patients see substantial tumor shrinkage with standard chemotherapy, and people with the disease survive for an average of just a year after they are diagnosed. More than 228,000 people this year will be diagnosed with the disease in the U.S., and the American Cancer Society estimates that nearly 143,000 will die of lung cancer in 2019.
— Denise Heady
“Five-Year Overall Survival for Patients with Advanced Non?small-cell Lung Cancer Treated with Pembrolizumab: Results from the Phase I KEYNOTE-001 Study,” Journal of Clinical Oncology, June 2, 2019
