Durvalumab misses survival endpoints in PEARL trial in NSCLC

January 2023 Cancer trials Nalinee Pandey
Lung cancer. lung disease

According to an update from the phase III PEARL trial, durvalumab (AstraZeneca’s Imfinzi) failed to significantly improve overall survival (OS) as a frontline treatment option in patients with stage IV non–small cell lung cancer (NSCLC) with high expression (25% or more) of PD-L1 or in a subgroup of patients at low risk of early mortality as compared to platinum-based chemotherapy. However, a clinically meaningful improvement in OS was seen in patients with 50% or a higher expression of PD-L1.

Durvalumab is a monoclonal antibody against PD-L1 that blocks PD-L1 ‘s interaction with PD-1 and thus prevents tumour cells from evading the immune response. The PEARL study compared the efficacy of Durvalumab immunotherapy against standard platinum-based chemotherapy.

The multicentre, open, randomised, phase III global PEARL study enrolled NSCLC patients with high PD-L1 expression (≥25%). The participants were primarily Asian, including smokers and non-smokers with squamous and non-squamous histology, excluding those with EGFR or ALK alterations. The study’s primary endpoints were OS in patients with high PD-L1 expression and OS in subgroups with a low risk of early mortality.

Durvalumab treatment for patients with metastatic NSCLC in a frontline setting showed encouraging results only in a subgroup of patients with high expression of PD-L1 (50% or more). The treatment regimen was safe and tolerable, with no new safety signals reported.


Update on PEARL phase III trial of Imfinzi monotherapy in stage IV non-small cell lung cancer. News release. AstraZeneca. December 19, 2022. Accessed December 19, 2022.