Beyond chemoradiotherapy: improving treatment outcomes for patients with stage III unresectable non-small-cell lung cancer through immuno-oncology and durvalumab (Imfinzi®â–¼, AstraZeneca UK Limited).

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®â–¼, 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.