The PD-L1 inhibitor durvalumab increases progression-free survival and objective response rate in patients with inoperable and locally advanced stage III non–small cell lung cancer, according to interim results of a phase III trial. The benefit was great enough that the drug could become the standard of care in the United States for these patients.

Durvalumab (Imfinzi; AstraZeneca) boosts progression-free survival in patients with stage III non–small cell lung cancer (NSCLC), according to a new study and data presented at the ESMO 2017 Congress, the annual meeting of the European Society for Medical Oncology, in Madrid, Spain.

About 60,000 to 80,000 people are diagnosed with stage III NSCLC each year in the United States. Although chemotherapy and radiation can lead to long-term survival, only about 15% of patients who receive that combination survive 5 years. “Eighty-five percent of patients aren't cured” by chemoradiotherapy, says Scott Antonia, MD, of the H. Lee Moffitt Cancer Center and Research Institute in Tampa, FL.

The PD-L1 inhibitor durvalumab, which received accelerated approval earlier this year for patients with locally advanced or metastatic urothelial carcinoma, is the first immunotherapy tested in patients with stage III NSCLC. In the phase III PACIFIC trial, Antonia and colleagues evaluated the drug in 713 patients diagnosed with inoperable, locally advanced disease who had recently received concurrent treatment with platinum-based chemotherapy and radiotherapy. Within 1 to 42 days after completing chemoradiotherapy, patients were randomly assigned in a 2:1 ratio to receive either durvalumab or a placebo. The patients in the durvalumab group received the drug for up to 12 months; those in the control group received no further treatment.

Based on the interim analysis, progression-free survival (PFS) was 16.8 months in the durvalumab group and 5.6 months in the controls. PFS didn't depend on patients' PD-L1 levels before chemoradiotherapy, the researchers found. “With this dramatic improvement in progression-free survival, it's likely that patients are deriving significant benefit” from the drug, Antonia says.

The objective response rate was 28.4% in the durvalumab group and 16% in the placebo group, which researchers attributed to a residual effect of the chemoradiotherapy. The drug also increased the median time to death or distant metastasis by 8.6 months. Patients who received the drug were also less likely than control patients to develop new lesions— 20.4% versus 32.1%, respectively.

These improvements came with a small cost: Grade 3 or 4 side effects were more common in the durvalumab group, 29.9% versus 26.1%. The most common serious side effect, pneumonia, was slightly more prevalent in the durvalumab patients, 4.4% versus 3.8%.

On the strength of these data, the FDA granted the drug Breakthrough Therapy designation for NSCLC.

“The results are extremely promising,” says Martin Edelman, MD, of the Fox Chase Cancer Center in Philadelphia, PA, who wasn't part of the research but did serve on the committee overseeing patient safety for this and other trials. “The experimental arm clearly and substantially benefitted without an unacceptable increase in toxicity,” says Edelman.

“This trial is practice-changing,” says Paul Bunn, MD, of the University of Colorado Denver School of Medicine, who also wasn't connected to the research. He predicts that durvalumab will become the standard of care in the United States. Bunn notes, however, that the crucial data on overall survival aren't in yet. “Everything would be different for this drug if there was no difference in survival,” Bunn says. –Mitch Leslie

©2017 American Association for Cancer Research.
2017
American Association for Cancer Research.