A new study by UCLA scientists has found that the breakthrough immunotherapy drug pembrolizumab can be more effective in improving survival in people with non-small cell lung cancer (NSCLC) if they have previously received radiation therapy, compared to those without a history of radiation treatment. The findings are important as the strategies of combining radiation therapy with anti-PD-1 antibodies such as pembrolizumb are currently being explored, and have the potential to increase the overall benefit of immunotherapy for people with NSCLC, the most common form of lung cancer.
The research is published online in The Lancet Oncology.
Immunotherapy using anti-PD-1 antibodies has revolutionized the treatment of NSCLC and a growing list of other cancers. Pembrolizumab (marketed as Keytruda) is an antibody that targets the protein PD-1, and works by turning off the immune system’s brakes, allowing its T cells to recognize and attack cancer cells. However, less than 20 percent of people with NSCLC respond to these treatments, and new strategies are needed in order to boost the cancer-killing power of anti-PD-1 immunotherapies.
Previous pre-clinical studies have shown that radiation therapy in combination with anti-PD-1 antibodies can synergistically improve the ability of anti-PD-1 antibodies to stimulate the body’s immune response to tumors. Recent research suggests that combining radiation therapy with anti-PD-1 therapies can further enhance the immune system’s ability to detect and fight cancer, but more clinical data is needed, said Dr. Percy Lee, associate professor and vice chair of education in the department of radiation oncology at the David Geffen School of Medicine and a senior author of the study.
Lee and Dr. Narek Shaverdian, a clinician-scientist at the David Geffen School of Medicine and first author of the study, hypothesized that patients with NSCLC who had previously received extracranial radiation therapy (radiation therapy for their lung cancer at sites outside of the brain) would see an increase in anti-tumor activity after receiving pembrolizumab. The UCLA team also sought to determine if previous radiation therapy to the lungs would increase the side effects of pembrolizumab in lung cancer patients receiving this therapy.
In the multidisciplinary study, the UCLA researchers performed a secondary analysis of 97 patients with NSCLC who were treated with pembrolizumab as part of a previous phase 1 KEYNOTE-001 clinical trial. The UCLA team divided the trial participants into subgroups to compare patients who had previously received radiation therapy for the treatment of their NSCLC to those patients who did not receive any prior radiation therapy.
The results showed that patients who previously received extracranial radiation therapy had a significantly longer median progression-free survival (the length of time before a patient's cancer worsens) of 6.3 months, compared to 2.0 months for patients who did not previously receive radiation therapy. The patients that received radiation therapy were also found to live significantly longer than those that did not (11.6 months versus 5.3 months), Shaverdian said.
Patients who received prior radiation therapy to the chest (called thoracic radiation therapy) had more treatment related pulmonary toxicity (13 to 1 percent) following pembrolizumab treatment compared to those who received other types of radiation therapy or no radiation at all. There was no significant difference in the rates of high-grade pulmonary toxicities with pembrolizumab between patients with and without prior thoracic radiation therapy, Lee said.
Lung cancer is the leading cause of cancer deaths worldwide, and the American Lung Association estimates more than 158,000 people in the United States will die from the disease this year alone. NSCLC accounts for approximately 85 percent of all lung cancers.
These new findings represent the largest clinical data analysis on the clinical impact of prior radiation therapy on enhancing the activity of anti-PD-1 therapies in people with NSCLC, and support extensive prior pre-clinical studies showing the potential benefit of this treatment strategy for people with NSCLC. The study can also help to better identify patient populations who may stand to benefit from the combination of radiation therapy and anti-PD-1 therapies, and lead to the development of new and improved treatments for advanced lung cancer and other diseases.
Future UCLA studies will evaluate the effectiveness of the radiation therapy in combination with pembrolizumab and other immunotherapies in both early and late stages of lung cancers as well as potentially for other types of cancers, Lee said.
The study’s first authors are Drs. Narek Shaverdian and Aaron E. Lisberg at the David Geffen School of Medicine at UCLA; the senior co-authors are Drs. Percy Lee and Edward Garon. Other authors include Krikor Bornazyan, Darlene Veruttipong and Jonathan W. Goldman of UCLA; and Silvia C. Formenti of Weill Cornell Medicine. Garon, Goldman and Lee are members of UCLA’s Jonsson Comprehensive Cancer Center.
The research was supported by the National Institutes of Health.
UCLA’s Jonsson Comprehensive Cancer Center has more than 500 researchers and clinicians engaged in cancer research, prevention, detection, control, treatment and education. One of the nation's largest comprehensive cancer centers, the Jonsson Comprehensive Cancer Center is dedicated to promoting research and translating basic science into leading-edge clinical studies. In August 2016, UCLA Health medical centers ranked among the top five hospitals for adult cancer care nationwide by U.S. News & World Report.