PACIFIC: Practice-Changing Study in Stage III Unresectable Non–Small-Cell Lung Cancer
Toronto, Canada—The PD-L1 inhibitor durvalumab (Imfinzi) showed an overall survival benefit in patients with unresectable stage III non–small-cell lung cancer (NSCLC) in the phase 3 PACIFIC trial.
Durvalumab improved survival by 32% versus placebo in patients whose disease had not progressed on concurrent chemoradiotherapy. This is the first time a study has demonstrated a survival advantage, and the study results suggest that durvalumab will be a new standard of care in this setting.
The results of the study were greeted with enthusiasm at the 2018 International Association for the Study of Lung Cancer World Conference on Lung Cancer, and were published simultaneously in the New England Journal of Medicine.1
The survival analysis showed a statistically significant and clinically meaningful difference in overall survival for durvalumab versus placebo in patients with unresectable stage III NSCLC.
“We saw improvements in progression-free survival, time to distant metastases, and emergence of new lesions with durvalumab, and the drug was well-tolerated.
“This is the first study in many years to support a survival advantage for unresectable stage III NSCLC with no progression following chemoradiotherapy,” said lead investigator Scott J. Antonia, MD, PhD, Department Chair, Thoracic Oncology Department, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL.
“PACIFIC is a positive trial with a 32% improvement in survival, and is a new standard of care,” according to Everett E. Vokes, MD, Chair, Department of Medicine, University of Chicago, IL, who was formal discussant of the trial.
Approximately 15% to 30% of patients with locally advanced, unresectable stage III NSCLC are cured with conventional chemotherapy and radiotherapy with curative intent.
“We’ve been stuck with those numbers for decades. Last year, we saw an 11.2-month improvement in progression-free survival with durvalumab in the PACIFIC trial. Today, we see improved overall survival,” Dr Antonia stated.
The randomized, placebo-controlled, phase 3 PACIFIC clinical trial was conducted at 235 investigative sites in 26 countries and enrolled 713 patients whose disease did not progress after chemoradiotherapy for unresectable stage III NSCLC.
Patients were randomized 2:1 to durvalumab or placebo 1 to 42 days after radiation and received treatment every 2 weeks for up to 12 months or until disease progression.
“We took all comers regardless of PD-L1 expression,” Dr Antonia told attendees.
The baseline characteristics were well-balanced between the 2 treatment arms. The 12-month OS rate was 83.1% for durvalumab versus 75.3% for placebo. The 24-month OS rate was 66.3% versus 55.6%, respectively.
The median OS was not reached in the durvalumab group and was 28.7 months in the patients receiving placebo, which is a 32% improvement in survival for patients receiving the PD-L1 inhibitor (P = .0025).
An updated analysis showed a median progression-free survival of 16.8 months with durvalumab versus 5.6 months with placebo (P <.001), which is an 11.2-month improvement.
PD-L1 testing was obtained before chemoradiotherapy. More than 33% of patients in the PACIFIC trial had unknown PD-L1 status. The patients with the lowest level (<1%) of PD-L1 expression did not benefit from durvalumab.
The time to distant metastasis or death was longer in the durvalumab group, at a median of 28.3 months versus 16.2 months for placebo.
No new safety signals emerged during the trial. Grade 3 or 4 adverse events of any cause occurred in 30.5% of the patients in the durvalumab group and 26.1% of patients in the placebo group.
Treatment discontinuations resulting from adverse events were reported in 15.4% and 9.8% of patients, respectively. The most frequent adverse events leading to discontinuation were pneumonitis (4.8% of the durvalumab group and 2.6% of patients receiving placebo).
Serious adverse events were reported in 29.1% of the durvalumab group and 23.1% of the placebo group. Death from adverse events occurred in 4.4% and 6.4% of patients, respectively.
- Antonia SJ, Villegas A, Daniel D, et al; for the PACIFIC investigators. Overall survival with durvalumab after chemoradiotherapy in stage III NSCLC. N Engl J Med. 2018 Sep 25. Epub ahead of print.