In a recent phase II clinical trial, the combination of the PD-L1 inhibitor durvalumab and the CTLA-4 inhibitor tremelimumab curtailed tumor growth in some patients with non–small cell lung cancer (NSCLC) that was resistant to a single immunotherapy agent. The addition of radiation therapy to the two-drug regimen did not improve outcomes, however, according to a report published by Jonathan Schoenfeld, MD, and colleagues in The Lancet Oncology.
The research is part of a broad-based effort to extend the benefits of immune checkpoint inhibitors by combining them with other treatments and with one another. The new trial is one of the first to test radiation therapy in combination with immune therapy in patients with cancer. The fact that radiation therapy didn’t enhance the effect of the two-drug therapy suggests that future studies should explore different combinations, the study authors said.
“Patients with NSCLC that doesn’t respond to … PD-1/PD-L1 inhibitors have few treatment options. In this trial, we tested a PD-L1 inhibitor in combination with a drug that targets a different immune checkpoint protein, CTLA-4—an approach that has shown promise in laboratory research but hasn’t been extensively tested in patients whose NSCLC is resistant to PD-1/PD-L1 inhibitors,” said Dr. Schoenfeld, of Dana-Farber Brigham Cancer Center.
Jonathan Schoenfeld, MD
“We not only found that the combination brought the cancer under control in some patients, but our laboratory work suggests a way of determining which patients are likely to have this benefit,” he remarked.
Trial Details
The trial involved 78 patients at 18 cancer centers in the United States. All participants received durvalumab at 1,500 mg intravenously every 4 weeks for a maximum of 13 cycles and tremelimumab at 75 mg intravenously every 4 weeks for a maximum of 4 cycles. One-third of enrolled patients were also treated with low-dose radiation therapy followed by durvalumab, and one-third were treated with higher-dose hypofractionated radiation therapy followed by durvalumab.
There was no difference in response rates between patients treated with radiation therapy and those in the immunotherapy-only group, investigators found. However, about 30% of the patients had their disease brought under control, including 10% who had long-lasting responses to treatment.
As part of the study, researchers analyzed tumor tissue samples from the participants. They found that those whose tumors teemed with immune system T cells were more likely to respond to the treatment than those with fewer T cells in their tumor tissue.
“Our findings suggest that durvalumab/tremelimumab should be further explored for its ability to benefit patients with NSCLC who have [had disease progression] on prior PD-1/PD-L1 therapy,” Dr. Schoenfeld said. “In future trials of these and similar agents, analyzing tumor tissue for T-cell infiltration may be able to identify patients who can most benefit from this type of treatment.”
Disclosure: The study was funded by the National Institutes of Health and Dana-Farber Cancer Institute. For full disclosures of the study authors, visit thelancet.com.
