Curative-Intent Treatment with Durvalumab in Early-Stage Cancers

Abstract

The introduction of immunotherapy has fundamentally transformed the treatment landscape in cancer, providing long-term survival benefit for patients with advanced disease across multiple tumor types, including non-small cell lung cancer (NSCLC). In the placebo-controlled phase 3 PACIFIC trial, the PD-L1 inhibitor durvalumab demonstrated significant improvements in progression-free survival and overall survival in patients with unresectable, stage III NSCLC who had not progressed after platinum-based chemoradiotherapy (CRT). These findings have led to the widespread acceptance of the 'PACIFIC regimen' (durvalumab after CRT) as the standard of care in this setting. Moreover, the PACIFIC trial is the first study to demonstrate a proven survival advantage with an immunotherapy in a curative-intent setting, thereby providing a strong rationale for further investigation of durvalumab in early-stage cancers. Herein, we describe the extensive clinical development program for durvalumab across multiple tumor types in curative-intent settings, outlining the scientific rationale(s) for its use and highlighting the innovative research (e.g., personalized cancer monitoring) advanced by these trials.

Keywords: Bladder cancer; Cervical cancer; Curative intent; Durvalumab; Early-stage cancer; Esophageal cancer; Gastric cancer; Hepatocellular carcinoma; Lung cancer; PACIFIC.

Fig. 1

Proposed mechanism of action for durvalumab after chemoradiotherapy [–49, 62]

Fig. 2

Proposed treatment management strategy to eradicate cancer and prevent resistance