Highlights from

World Conference on Lung Cancer

19th annual meeting

Toronto, Canada 23-26 September 2018

Durvalumab after chemoradiotherapy extends OS in stage 3, unresectable non-small-cell lung cancer

Updated overall survival (OS) data from the phase 3 PACIFIC trial have set a new standard of care for first-line treatment of unresectable stage 3 NSCLC. Previously reported results showed that durvalumab significantly improved progression-free survival (PFS) by 11.2 months compared with placebo (HR 0.52; 95% CI 0.42-0.65; P<0.001) [1]. The latest findings show a 2-year landmark survival rate of 66.3% for patients in the durvalumab group vs 55.6% in the placebo arm (P=0.005). Dr Scott Antonia (H. Lee Moffitt Cancer Center and Research Institute, USA) reported results at the live session [2]. The study was simultaneously published in the New England Journal of Medicine [3].

PACIFIC was a randomised, double-blind, placebo-controlled trial. A total of 709 patients with locally advanced, stage 3, unresectable NSCLC underwent concurrent chemoradiotherapy with no progression after treatment. Patients with any PD-L1 tumour status were enrolled into the study and randomised to receive intravenous durvalumab (n=473; 10 mg/kg of body weight) or placebo (n=236) every 2 weeks for up to 12 months. Randomisation occurred up to 42 days after concurrent chemoradiotherapy and was stratified according to age, sex, and smoking history. Primary endpoints were PFS and OS. Durvalumab is a selective human IgG1 monoclonal antibody that blocks PD-L1 binding to PD-1 and CD80, allowing T-cells to recognise and kill tumour cells [4,5].

Updated results showed that durvalumab significantly improved OS vs placebo (stratified HR 0.68; P=0.00251). Although the median OS had yet to be reached for durvalumab, it was 28.7 months for patients in the placebo arm. The survival benefit was seen in all prespecified subgroups. The median PFS was 17.2 vs 5.6 months for durvalumab and placebo, respectively. Findings on secondary outcomes also favoured durvalumab over placebo. There were no new safety issues. An unplanned post-hoc analysis, showed that OS was shorter (HR 1.36) in patients with tumour PD-L1 expression ≤1% who received durvalumab, but the finding was not statistically significant. Noteworthy, the group was relatively small and imbalances in baseline characteristics existed. OS outcomes from the PACIFIC trial provide compelling evidence for the benefit of durvalumab as the standard of care for patients with unresectable, stage 3 NSCLC.

  1. Antonia SJ, et al. N Engl J Med 2017;377:1919-1929.
  2. Antonia SJ, et al. Abstract PL02.01. IASLC 19th WCLC. 23-26 September 2018, Toronto, Canada.
  3. Antonia SJ, et al. N Engl J Med 2018:DOI: 10.1056/NEJMoa1809697.
  4. Ibrahim R, et al. Semin Oncol 2015;42:474-483.
  5. Stewart R, et al. Cancer Immunol Res 2015;3:1052-1062.

Article image: @ Luis M Molina

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