New data from the phase III PACIFIC trial of durvalumab in patients with stage III non–small cell lung cancer show that the drug increases the odds of surviving for 24 months. The study also confirms that progression-free survival and time to death or distant metastasis are longer for patients treated with durvalumab than for patients who received a placebo.

The FDA approved durvalumab (Imfinzi; AstraZeneca) earlier this year for certain patients with non–small cell lung cancer (NSCLC), based on progression-free survival (PFS) in the phase III PACIFIC trial. Now, new trial data show that the PD-L1 inhibitor also increases overall survival (OS) in these patients.

The FDA's decision cleared durvalumab for patients with stage III NSCLC that has not progressed after chemoradiation. Other potential treatments for this group have performed poorly in recent clinical trials. The START trial, for instance, found that the cancer vaccine tecemotide, which targets MUC-1 on tumor cells, did not increase OS.

That's why researchers were enthusiastic about the early results from the PACIFIC trial, led by Scott Antonia, MD, PhD, of the H. Lee Moffitt Cancer Center and Research Institute in Tampa, FL, in which 709 patients received either durvalumab or a placebo. The median PFS in the durvalumab group was 16.8 months, versus 5.6 months in the placebo group. The median time to death or distant metastasis was 8.6 months longer among patients who received durvalumab than in those who received a placebo.

The latest trial data, which the researchers presented at the 19th World Conference on Lung Cancer in Toronto, Canada, and in The New England Journal of Medicine, reveal that the patients who received durvalumab continued to fare better. PFS was 17.2 months among patients in the durvalumab group, versus 5.6 months for patients in the control group. The median time to death or distant metastasis was 28.3 months in patients treated with durvalumab and 16.2 months in patients who received a placebo.

The just-released OS data also show an advantage for the patients treated with durvalumab. Their 24-month survival was 66.3%, compared with 55.6% in the placebo group. “The survival curves have separated nicely,” says Antonia. “This is the first time in a couple of decades that a study has shown an increase in overall survival.”

The longer follow-up did not alter the drug's safety profile, the researchers found. In the earlier report, 29.9% of patients in the durvalumab group developed Grade 3 or 4 side effects, whereas 26.1% of the patients in the placebo group did. Those numbers barely changed in the new analysis—30.5% and 26.1%, respectively. Antonia says he and his colleagues did not detect any new side effects from the drug.

“The survival data was much anticipated, and it is very reassuring that the progression-free survival data translated into an overall survival gain,” says Jamie Chaft, MD, of Memorial Sloan Kettering Cancer Center in New York, NY, who wasn't connected to the study. But whether this approach is curing patients remains unclear, she says. Chemoradiation cures about 15% to 20% of patients with stage III NSCLC. Longer follow-up is necessary before researchers can determine whether durvalumab increases the cure rate, Chaft says.

Before durvalumab's approval, patients had no treatment options after they finished chemoradiation, notes Paul Bunn, MD, of the University of Colorado Denver School of Medicine. The updated data show that “the benefit is clearly significant and outweighs the risk,” he says. “It's more than enough to make this the standard of care.” –Mitch Leslie

©2018 American Association for Cancer Research.
2018
American Association for Cancer Research.