Beyond chemoradiotherapy: improving treatment outcomes for patients with stage III unresectable non-small-cell lung cancer through immuno-oncology and durvalumab (Imfinzi®▼, AstraZeneca UK Limited)

Br J Cancer. 2020 Dec;123(Suppl 1):18-27. doi: 10.1038/s41416-020-01071-5.

Abstract

The treatment paradigm of non-small-cell lung cancer (NSCLC) has rapidly changed in recent years following the introduction of immune-checkpoint inhibition (ICI). Pre-clinically, both chemotherapy and radiotherapy modulate the tumour microenvironment, providing the rationale for clinical trials evaluating their role in combination with immunotherapy. Standard-of-care treatment for patients with unresectable stage III disease is concurrent chemoradiotherapy (cCRT); however, only recently, the combination with ICI has been explored. The Phase 3 PACIFIC study randomised 713 patients with confirmed locally advanced, unresectable, stage III NSCLC, whose disease has not progressed following cCRT, to either the anti-programmed death-ligand 1 (PD-L1) agent durvalumab (Imfinzi®▼, AstraZeneca UK Limited) or placebo. Patients with a PD-L1 status ≥1% treated with durvalumab had a significantly longer median progression-free survival compared with placebo (17.2 vs. 5.6 months, respectively; HR: 0.51; 95% CI: 0.41-0.63), prolonged median overall survival (OS) (NR vs. 28.7 months, respectively; HR: 0.68; 99.73% CI: 0.47-0.997; P = 0.0025) and long-term clinical benefit (3-year OS HR: 0.69; 95% CI: 0.55-0.86). Grade 3 or 4 toxicity was marginally greater in the durvalumab cohort versus placebo (30.5% vs. 26.1%). Based on these results, durvalumab has been licensed in this setting, and further clinical trials are exploring the use of ICI in unresectable stage III NSCLC.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Antibodies, Monoclonal / adverse effects
  • Antibodies, Monoclonal / therapeutic use*
  • Antineoplastic Agents, Immunological
  • B7-H1 Antigen / adverse effects
  • B7-H1 Antigen / genetics
  • Carcinoma, Non-Small-Cell Lung / drug therapy*
  • Carcinoma, Non-Small-Cell Lung / epidemiology
  • Carcinoma, Non-Small-Cell Lung / immunology
  • Carcinoma, Non-Small-Cell Lung / radiotherapy
  • Chemoradiotherapy / adverse effects*
  • Humans
  • Immunotherapy
  • Progression-Free Survival
  • Treatment Outcome
  • Tumor Microenvironment / drug effects*

Substances

  • Antibodies, Monoclonal
  • Antineoplastic Agents, Immunological
  • B7-H1 Antigen
  • CD274 protein, human
  • durvalumab