For years, the standard of care for patients with unresectable, locally advanced (stage III) non–small-cell lung cancer (NSCLC) and a good performance status has been platinum-based doublet chemotherapy combined with radiotherapy (chemoradiotherapy [CRT]). Clinical results associated with CRT, however, remain poor—at 5 years, only 15% of these patients are alive and 12% are free from disease progression.1
The ongoing phase 3 PACIFIC study is a randomized, double-blind, placebo-controlled, multicenter trial of durvalumab as consolidation therapy for patients with unresectable, locally advanced NSCLC who have not progressed following platinum-based CRT. The primary end points of the trial are progression-free survival (PFS) and overall survival (OS); secondary end points include landmark PFS and OS, objective response rate, and duration of response.2,3
Durvalumab (Imfinzi) is a selective, high-affinity, human IgG1 monoclonal antibody that blocks programmed death ligand 1 (PD-L1). On May 1, 2017, the FDA granted accelerated approval to durvalumab for the treatment of patients with locally advanced or metastatic urothelial carcinoma who have disease progression during or following platinum-containing chemotherapy, or who have disease progression within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy.2
Interim results of the PACIFIC trial were presented at the European Society for Medical Oncology Congress in Madrid, Spain, in September 2017. After randomization, 473 patients with stage III NSCLC received durvalumab consolidation and 236 patients received placebo. The median PFS from randomization was 16.8 months with durvalumab compared with 5.6 months with placebo (stratified hazard ratio for disease progression or death, 0.52; 95% confidence interval, 0.42-0.65; P <.001).3,4 The 1-year PFS rates were 55.9% for durvalumab consolidation and 35.3% for placebo; 18-month PFS rates were 44.2% and 27.0%, respectively.3,4 The PFS benefit was observed across all prespecified subgroups and irrespective of baseline expression of PD-L1 on tumor cells.3
The most frequent treatment-related adverse events (AEs) in the durvalumab and placebo groups, respectively, were cough (35.4% vs 25.2%), pneumonitis/radiation pneumonitis (33.9% vs 24.8%), fatigue (23.8% vs 20.5%), dyspnea (22.3% vs 23.9%), and diarrhea (18.3% vs 18.8%). Grade 3/4 AEs were observed in 29.9% of durvalumab-treated patients compared with 26.1% of patients receiving placebo; 15.4% of patients in the durvalumab group discontinued treatment because of AEs versus 9.8% of patients in the placebo group.3
“For patients with locally-advanced unresectable NSCLC who have completed chemoradiation therapy, Imfinzi represents a potential new treatment option in the context of clear unmet clinical need. Durvalumab overtly prolongs the period in which the disease is controlled with reasonable side effects. In addition, it offers hope to increase the cure rate in this setting, but more mature follow-up is needed to assess its impact on survival,” said Luis Paz-Ares, MD, Professor of Medicine at the Hospital Universitario Doce de Octubre, Madrid, Spain, and Principal Investigator of the PACIFIC trial, in a recent press release.3
On July 31, 2017, durvalumab received breakthrough therapy designation from the FDA as a potential treatment for patients with locally advanced, unresectable NSCLC whose disease has not progressed following platinum-based CRT. As of September 2017, the developer of durvalumab was discussing regulatory submission of data from the PACIFIC trial with global health authorities.3
1. Aupérin A, Le Péchoux C, Rolland E, et al. Meta-analysis of concomitant versus sequential radiochemotherapy in locally advanced non-small-cell lung cancer. J Clin Oncol. 2010;28:2181-2190.
2. US Food and Drug Administration. AstraZeneca’s Imfinzi (durvalumab) receives US FDA accelerated approval for previously treated patients with advanced bladder cancer. www.astrazeneca.com/media-centre/press-releases/2017/astrazenecas-imfinzi-durvalumab-receives-us-fda-accelerated-approval-for-previously-treated-patients-with-advanced-bladder-cancer-01052017.html. Accessed January 25, 2018.
3. AstraZeneca. AstraZeneca presents superior progression-free survival for Imfinzi in the PACIFIC trial of patients with locally-advanced unresectable lung cancer at ESMO 2017 Congress. www.astrazeneca.com/media-centre/press-releases/2017/astrazeneca-presents-superior-progression-free-survival-for-imfinzi-in-the-pacific-trial-of-patients-with-locally-advanced-unresectable-lung-cancer-at-esmo-2017-congress-08092017.html. Accessed January 25, 2018.
4. Antonia SJ, Villegas A, Daniel D, et al. Durvalumab after chemoradiotherapy in stage III non–small-cell lung cancer. N Engl J Med. 2017;377:1919-1929.