TORONTO – The programmed death-ligand 1 (PD-L1) inhibitor durvalumab significantly improves overall survival in patients with stage III unresectable non–small-cell lung cancer without progression after chemoradiotherapy, according to updated results from the global phase 3 PACIFIC study.
Sharon Worcester/MDedge News
Dr. Scott J. Antonia
The findings, presented at the World Conference on Lung Cancer, follow a prior report from the study showing improved progression-free survival (PFS) in durvalumab-treated patients (stratified hazard ratio, 0.52), and together these survival benefits mark the first major advance in this disease setting in decades,” Scott J. Antonia, MD, reported at the conference, sponsored by the International Association for the Study of Lung Cancer (IASLC).
“The fact is this is a new standard of care treatment for the patients with this disease,” he said, adding that “in all likelihood we are improving the cure rate for the patients with this disease.”
The findings were published simultaneously in the New England Journal of Medicine.
Overall survival at a median follow-up of 25.2 months in 473 patients randomized to receive durvalumab was significantly greater than among 236 who received placebo (stratified HR, 0.68; median survival not reached vs. 28.7 months in the groups, respectively), said Dr. Antonia of the H. Lee Moffitt Cancer Center and Research Institute, and professor of oncologic sciences at the University of South Florida, Tampa.
Durvalumab also improved overall survival in all prespecified subgroups, and PFS was similar to that in previous reports (stratified HR 0.51; median of 17.2 vs. 5.6 months with durvalumab and placebo, respectively), he said, noting that “interestingly, patients who were nonsmokers did benefit from durvalumab.”
This is notable because prior research suggests that never-smokers with advanced stage cancer have less of a chance of responding to immunotherapy (although they should still be offered immunotherapy), he explained.
“Also interestingly, it appears as if cisplatin was the better drug to use in the conventional therapy portion of the treatment,” he said.
Durvalumab also provided continued improvement vs. placebo in time to death or distant metastasis (stratified HR, 0.53), time to second progression (stratified HR, 0.58), time to first subsequent therapy or death (stratified HR, 0.58), and time to second subsequent therapy or death (stratified HR, 0.63).
Study subjects were patients with World Health Organization Performance Status scores of 0 or 1 with any PD-L1 tumor status, who received at least two cycles of conventional standard-of-care platinum-based chemoradiotherapy (CRT). They were randomized between May 2014 and April 2016 – at 1-42 days after CRT – to receive intravenous durvalumab at a dose of 10 mg/kg given intravenously every 2 weeks or placebo, and were stratified by age, gender, and smoking history.
Durvalumab was well tolerated; 30.5% and 26.1% of treatment and placebo patients, respectively, had grade 3/4 adverse events, and 15.4% and 9.8%, respectively, discontinued because of adverse events.
“There were no new safety signals with this longer follow-up,” Dr. Antonia said.
After study treatment ended, 41% and 54% in the groups, respectively, received additional anticancer therapy, and 8% and 22.4%, respectively, received additional immunotherapy, he noted.
The results are not only statistically significant, but clinically meaningful, and they offer new hope for patients with a disease that, in those who receive chemoradiotherapy, has a 3-year survival rate of only about 27%, he said.
During a press briefing at the conference, moderator Frances Shepherd, MD, a medical oncologist at Princess Margaret Cancer Centre in Toronto and a past president of the International Association for the Study of Lung Cancer, called the results “very exciting” given that this type of cancer represents about a third of all lung cancers and therefore affects an “enormous number of patients in Canada and globally.”
Sharon Worcester/MDedge News
Dr. Frances Shepherd
The PACIFIC trial was sponsored by AstraZeneca. Dr. Antonia reported being a speaker or advisory board member or receiving funding support from AstraZeneca and numerous other companies. Dr. Shepherd reported receiving honoraria and support from AstraZeneca and others. She is a speaker or advisory board member for Eli Lilly, AstraZeneca, and Merck, and she has ownership Interest in Eli Lilly and AstraZeneca.
SOURCE: Antonia S et al., WCLC 2018 Abstract PL02.01.