Durvalumab, a PD-L1 inhibitor, improved progression-free survival (PFS) by 11.2 months compared with placebo in patients with locally advanced, unresectable stage III non–small cell lung cancer (NSCLC) that did not progress after standard treatment with chemoradiotherapy, according to results presented at the ESMO 2017 Congress.
These results represent the first phase 3 trial of a PD-L1 inhibitor in locally advanced NSCLC outside the metastatic setting.
“We saw a clear improvement in outcome versus placebo. Progression-free survival improved with durvalumab across all prespecified end points. Durvalumab is a promising new therapeutic option for patients with stage III locally advanced NSCLC,” said Luis Paz-Ares, MD, Chair of the Medical Oncology Department at Hospital Universitario Doce de Octubre, Madrid, Spain.
Most patients who present with stage III NSCLC at diagnosis are not resectable. Despite standard treatment with platinum-based chemotherapy and concurrent radiation therapy, most patients will relapse, and 5-year survival is only 15%.
Dr Paz-Ares suggested that the PD-L1 inhibitor extends the duration of disease control, improving PFS by more than 11 months.
“We haven’t analyzed survival data yet, but we hope we can increase the percentage of patients alive at 5 years with this therapy,” he said.
In July 2017, durvalumab received a breakthrough therapy designation from the FDA as a potential treatment for locally advanced, unresectable NSCLC that has not progressed following chemoradiation.
The PACIFIC trial is conducted at 235 centers in 26 countries and included 713 patients with locally advanced, nonresectable stage III NSCLC who had not progressed after platinum-based chemotherapy and concurrent radiation therapy for up to 42 days.
Patients were randomized 2:1 to receive durvalumab 10 mg/kg every 2 weeks or placebo for up to 12 months.
At baseline, response rates to chemotherapy were similar between the arms: 50.6% for durvalumab and 49.8% for placebo.
At a preplanned interim analysis at 14.5 months, median PFS was 16.8 months in the durvalumab arm versus 5.6 months with placebo, for a 48% reduction in the likelihood of disease progression with durvalumab (hazard ratio, 0.52; P <.0001).
At 18 months, PFS rates were 44.2% for durvalumab and 27% for placebo. Overall survival data are not yet mature.
The study included unselected patients for PD-L1 expression. Patient subgroups with either PD-L1–positive or PD-L1–negative tumors both benefited from durvalumab.
The overall response rate following treatment with durvalumab was 28.4% versus 16% for placebo. The complete response rate was 1.4% for durvalumab versus 0.5% for placebo. Median duration of response was not yet reached in the durvalumab arm versus 13.8 months with placebo.
Adverse events of all grades were reported in 96.8% in the durvalumab group and 94.9% in the placebo group. Grade 3/4 adverse events occurred in 29.9% versus 26.1%, respectively. Treatment-related adverse events occurred in 67.5% and 53.4%, respectively; serious adverse events were reported in 28.6% and 22.6%, respectively.
Comment on PACIFIC Trial
Formal discussant of this trial, Johan Vansteenkiste, MD, University Hospitals Leuven, Belgium, said: “We had an earthquake of immunotherapy in lung cancer last year at ESMO. After an earthquake, there is a tsunami of risk versus benefit. I think the results of PACIFIC represent a tsunami of benefit.”
“This is the first strong interim analysis of progression-free survival in a phase 3 trial for systemic therapy for stage III NSCLC in decades,” he emphasized. “Overall survival results will have more weight. For sure, we need to follow these data for survival in the curative setting. Three overall survival analyses are planned for PACIFIC.”