Deep diving in the PACIFIC: Practical issues in stage III non-small cell lung cancer to avoid shipwreck

Abstract

After publication of the PACIFIC trial results, immune checkpoint inhibitor-based immunotherapy was included in the treatment algorithm of locally advanced non-small cell lung cancer (NSCLC). The PACIFIC trial demonstrated that 12 mo of durvalumab consolidation therapy after radical-intent platinum doublet chemotherapy with concomitant radiotherapy improved both progression-free survival and overall survival in patients with unresectable stage III NSCLC. This is the first treatment in decades to successfully improve survival in this clinical setting, with manageable toxicity and without deterioration in quality of life. The integration of durvalumab in the management of locally advanced NSCLC accentuates the need for multidisciplinary, coordinated decision-making among lung cancer specialists, bringing new challenges and controversies as well as important changes in clinical work routines. The aim of the present article is to review—from a practical, multidisciplinary perspective—the findings and implications of the PACIFIC trial. We evaluate the immunobiological basis of durvalumab as well as practical aspects related to programmed cell death ligand 1 determination. In addition, we comprehensively assess the efficacy and toxicity data from the PACIFIC trial and discuss the controversies and practical aspects of incorporating durvalumab into routine clinical practice. Finally, we discuss unresolved questions and future challenges. In short, the present document aims to provide clinicians with a practical guide for the application of the PACIFIC regimen in routine clinical practice.

Keywords: Durvalumab, Non-small cell lung cancer, PACIFIC, Immunotherapy, Immune checkpoint inhibitors, Anti-programmed cell death ligand 1, Consolidation therapy, Unresectable stage III lung cancer

Core Tip: Durvalumab consolidation therapy is the new standard of care in patients with unresectable stage III non-small cell lung cancer treated with concomitant chemoradiotherapy. In the PACIFIC trial, durvalumab significantly improved both progression-free survival and overall survival compared to placebo, with a manageable toxicity profile. However, several questions surrounding the clinical implementation of this therapy remain including optimal patient selection and timing of treatment initiation, programmed cell death ligand 1 determination, and the impact on clinical routines. These questions make interdisciplinary decision-making more necessary than ever. This review assesses these issues and future challenges from a multidisciplinary approach.