Progression-free survival (PFS) was significantly improved with durvalumab when used as consolidation therapy in patients with locally-advanced, unresectable non–small cell lung cancer (NSCLC) who had not progressed following standard care with platinum-based concurrent chemoradiotherapy, according to results from the phase III PACIFIC trial that were reported at ESMO 2017, the Annual Congress of the European Society for Medical Oncology in Madrid, Spain.
The PACIFIC met its primary endpoint of improved PFS with durvalumab, an anti-PD-L1 (programmed death ligand-1) monoclonal antibody, in patients with locally advanced tumours for whom surgery was not an option.
Presenting author Luis Paz-Ares, Medical Oncology, Hospital Universitario 12 de Octubre, CiberOnc, Universidad Complutense and CNIO in Madrid, Spain communicated interim results from the double-blind PACIFIC trial (NCT02125461), which was carried in patients with unresectable, locally-advanced, (stage III) NSCLC and any level of PD-L1 expression who showed no disease progression after ≥2 cycles of platinum-based platinum-based chemoradiotherapy.
One to 42 days after undergoing chemoradiotherapy, 713 patients were randomised in a 2:1 ratio to durvalumab at 10 mg/kg i.v. every 2 weeks or placebo for up to 12 months. In all, 473 patients were treated with durvalumab and 236 received placebo. Patients were also stratified by age, sex, and smoking history. The PFS by blinded independent central review per RECIST v1.1 was a co-primary endpoint, along with overall survival (OS). Secondary endpoints included 12- and 18-month PFS rates, objective response rate (ORR), duration of response (DoR), time to death or distant metastasis (TTDM), and safety.
The co-primary endpoint of progression-free survival was met in PACIFIC
As of data cut-off on 13 February 2017, the median follow-up was 14.5 months.
Median PFS was significantly longer with durvalumab at 16.8 months; 95% confidence interval [CI] 13.0, 18.1 versus 5.6 months, 95% CI 4.6, 7.8 with placebo, stratified hazard ratio [HR] 0.52; 95% CI 0.42,0.65 (p < 0.0001).
The 12- and 18-month PFS rates with durvalumab versus placebo were 55.9% versus 35.3%, and 44.2% versus 27.0%, respectively.
The ORR was significantly higher with durvalumab at 28.4% compared to 16.0% with placebo (p < 0.001). Responding patients demonstrated a longer median DoR, which was not reached versus 13.8 months with placebo.
Significantly prolonged median TTDM was observed with durvalumab over placebo; TTDM was 23.2 versus 14.6 months, respectively, stratified HR 0.52; 95% CI 0.39, 0.69 (p < 0.0001).
The OS data were not yet mature at the time of the interim PFS analysis.
Adverse events (AEs) were similar between durvalumab and placebo, with grade 3/4 AEs occurring in 32.0% versus 27.8% patients; the most common AE was pneumonia, which occurred in 4.4% versus 4.3% of patients, respectively.
Study treatment was discontinued by 15.4% of patients receiving durvalumab and by 9.8% of patients on placebo.
PACIFIC data support FDA breakthrough approval for durvalumab in this setting
On 31 July 2017, the US Food and Drug Administration (FDA) granted breakthrough therapy designation to durvalumab for patients with locally advanced, unresectable NSCLC who do not relapse after platinum-based chemoradiation, based on data from this interim analysis of the phase III PACIFIC trial.
Durvalumab demonstrated significant and clinically meaningful improvement in PFS, which was supported by secondary endpoints, and was well tolerated.
Durvalumab is a promising therapeutic option in this setting.
Johan Vansteenkiste of the Respiratory Oncology Unit, Department of Pulmonology, University Hospital KU Leuven, Leuven, Belgium, who discussed the study results said that it’s a first strong “interim-PFS” positive phase III trial on systemic therapy for stage III NSCLC over decades.
Results have been simultaneously published in The New England Journal of Medicine. Antonia SJ, Villegas A, Daniel D, et al. Durvalumab after Chemoradiotherapy in Stage III Non–Small-Cell Lung Cancer. NEJM; Published online September 8, 2017. DOI: 10.1056/NEJMoa1709937.
This trial was sponsored by AstraZeneca.
LBA1_PR - Paz-Ares L, et al. PACIFIC: A double-blind, placebo-controlled Phase III study of durvalumab after chemoradiation therapy (CRT) in patients with Stage III, locally advanced, unresectable NSCLC.