McGahan, L. : Durvalumab (Imfinzi™) for the treatment of patients with stage III non-small-cell lung cancer after prior chemoradiotherapy. DSD: Horizon Scanning in Oncology 76.
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Durvalumab, a monoclonal antibody, is an immune checkpoint inhibitor. By blocking PD-L1 (programmed cell death-1) from binding to PD-1 and CD80 receptors, durvalumab restores T-cell activation, enabling the effective detection and destruction of tumour cells. In July 2017, the FDA granted durvalumab breakthrough therapy designation for the treatment of patients with stage III non-small cell lung cancer (NSCLC), whose disease had not progressed following platinum-based chemoradiotherapy. Currently, durvalumab is not approved in Europe.
In the phase III, PACIFIC study, 713 patients with stage III, unresectable NSCLC, without progression following platinum-based chemotherapy, were randomised 2:1 to durvalumab (10 mg/kg IV every 2 weeks) or matching placebo for up to 12 months. At a median follow-up of 14.5 months, durvalumab increased the median progression-free survival (PFS) by 11.2 months, compared to placebo, irrespective of PD-L1 expression level prior to chemoradiotherapy. Durvalumab also increased the overall response rate (ORR) by 12.4%, duration of response (DOR) (>13.8 months), time to death or distant metastasis (TTDM) by 9 months, and reduced the incidence of new brain metastases by 5.5% compared with placebo. Immune-mediated, treatment-related adverse events (AEs) requiring glucocorticoids or endocrine therapy were more commonly reported in the durvalumab group; pneumonitis and pneumonia resulted in discontinuation in 6.3% and 1.1% of durvalumab recipients, respectively.
Overall, durvalumab increases PFS, ORR, DOR, and TTDM in patients with stage III NSCLC, regardless of PD-L1 expression level prior to chemoradiation or histology, compared to placebo. However, overall survival (OS), quality of life (QoL) and long-term safety data are awaited, and study participants may not be representative of those in clinical practice. Direct comparison trials are lacking, to other immunotherapies (e.g. pembrolizumab), and cross-trial comparisons are cautioned due to differences in patient selection based on different PD-L1 assays. Further research is needed regarding the duration and timing of immunotherapy, the best regimen of chemoradiation for combination, and patient selection for greatest benefit based on predictive markers of efficacy and resistance.
|Item Type:||DSD: Horizon Scanning in Oncology|
|Keywords:||Durvalumab, Imfinzi, non-small cell lung cancer, NSCLC, lung cancer|
|Subjects:||WB Practice of medicine > WB 300-962 Therapeutics|
QZ Pathology > QZ 200-380 Neoplasms.Cysts
WF Respiratory system
QV Pharmacology, toxicology, pharmacy > QV 60-370 Pharmacology
|Series Name:||DSD: Horizon Scanning in Oncology 76|
|Deposited on:||22 Dec 2017 16:54|
|Last Modified:||22 Dec 2017 16:54|
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