Durvalumab improves PFS after chemoradiotherapy in unresectable stage III NSCLC
Durvalumab was shown to provide significant improvements in progression-free survival (PFS) in patients with stage III, locally advanced, unresectable non-small-cell lung cancer (NSCLC) who have completed platinum-based concurrent chemoradiotherapy (cCRT), according to the phase III PACIFIC study. [ESMO 2017, abstract LBA1_PR; N Engl J Med 2017, doi: 10.1056/NEJMoa1709937]
“Approximately one-third of NSCLC patients present with stage III, locally advanced disease at diagnosis,” said Paz-Ares of the Hospital Universitario Doce de Octubre, Madrid, Spain. “The median PFS with standard-of-care is about 8–10 months, and the 5-year survival rate is 15 percent only.” [J Clin Oncol 2010;28:2181-2190; World J Clin Oncol 2017;8:1-20; J Clin Oncol 2015;33:2660-2666; J Clin Oncol 1999;17:2692-2699; Eur J Cancer 2007;43:114-121; J Clin Oncol 1999;17:4-11]
“PACIFIC is the first randomized phase III study that evaluates the efficacy of immune checkpoint blockade in patients with stage III NSCLC,” he continued.
In the study, 713 patients with stage III, locally advanced, unresectable NSCLC with no disease progression following ≥2 cycles of platinum-based chemotherapy plus radiotherapy (RT) were randomized to receive durvalumab 10 mg/kg Q2W (n=476) or placebo (n=237) for up to 12 months.
In the interim analysis conducted after a median follow-up of 14.5 months, median PFS was significantly improved by >11 months with durvalumab vs placebo (16.8 vs 5.6 months; hazard ratio [HR], 0.52; p<0.0001). The 12-month and 18-month PFS rates were 55.9 vs 35.3 percent and 44.2 vs 27.0 percent, respectively.
“The PFS benefit with durvalumab was consistent across all analyzed subgroups,” said Paz-Ares. “Notably, the HR for the PFS benefit with durvalumab was 0.41 and 0.59 in patients with PD-L1 expression ≥25 percent and <25 percent on tumour cells, respectively, with 95 percent confidence interval largely overlapping.”
Objective response rate was significantly higher with durvalumab vs placebo (28.4 vs 16.0 percent; p<0.001). The median duration of response was not reached in patients receiving durvalumab vs 13.8 months in those receiving placebo (HR, 0.43). Fewer patients in the durvalumab group had new lesions (20.4 vs 32.1 percent).
“In addition, patients receiving durvalumab had longer time to distant metastasis or death [median, 23.2 vs 14.6 months; HR, 0.52; p<0.0001],” noted Paz-Ares.
“Durvalumab was generally well tolerated. Its safety profile in the study was consistent with that previously reported in patients with more advanced disease and other immunotherapies. No new safety signals were identified,” he reported .
Grade 3/4 adverse events were reported in 29.9 percent of patients in the durvalumab group vs 26.1 percent in the placebo group. While any-grade pneumonitis was more common with durvalumab (24.2 vs 8.1 percent), rates of grade 3/4 pneumonitis were similar between durvalumab and placebo (3.4 vs 2.6 percent).
“The study remains blinded to overall survival [OS]. Final OS analysis will be performed when 491 deaths have occurred,” Paz-Ares added.
Durvalumab, previously known as MEDI4736, is a selective, human immunoglobulin G1 monoclonal antibody that blocks the binding of PD-L1 to PD-1 and CD80 proteins, allowing effector T cells to recognize and kill tumour cells. [Cancer Immunol Res 2015;3:1052-1062]