Durvalumab Versus Chemotherapy as First-line Treatment for Metastatic NSCLC With Tumor PD-L1 Expression of 25% or Higher: Results From the Randomized Phase 3 PEARL Study
Published report from the PEARL trial registered as NCT03003962, in Journal of Thoracic Oncology (2025), chosen as the most cited paper whose own text cites the registry id.
Overview
Introduction: PEARL (NCT03003962) is an open-label, phase 3 study comparing first-line durvalumab monotherapy with chemotherapy in patients with metastatic NSCLC (mNSCLC [EGFR/ALK wild type]) with programmed cell death ligand 1 (PD-L1) tumor cell (TC) membrane expression status of 25% or higher. We report the final analysis of PEARL.
Methods: Adults (N = 669) with previously untreated stage IV mNSCLC were randomized (1:1) to durvalumab 20 mg/kg every four weeks or chemotherapy every three weeks for four to six cycles. The dual primary endpoints were overall survival (OS) in the population with PD-L1 TC of 25% or higher and OS in the population at low risk of early mortality (LREM) with PD-L1 TC of 25% or higher.
Results: Durvalumab was associated with a numerical reduction in the risk of death versus chemotherapy in the 25% and higher PD-L1 TC population (OS hazard ratio [HR] = 0.84, 95% confidence interval [CI]: 0.71-0.99, p = 0.037; median OS 14.6 months, 95% CI: 12.2-16.9 versus 12.8 months, 95% CI: 10.1-14.7, respectively). In the 25% and higher PD-L1 TC low risk of early mortality population the OS hazard ratio for durvalumab versus chemotherapy was 0.96 (95% CI: 0.79-1.15, p = 0.628); median OS 14.6 months (95% CI: 12.6-17.2) versus 15.0 months (95% CI: 13.1-16.8), respectively. In the safety population, the incidence of grade 3 or 4 treatment-related adverse events was 15.5% (durvalumab) and 45.9% (chemotherapy).
Conclusions: Durvalumab did not statistically significantly improve OS versus chemotherapy as first-line treatment in patients with mNSCLC and 25% and higher PD-L1 TC. The numerical improvement in OS was consistent with previous studies of first-line immune checkpoint inhibitor monotherapy in patients with mNSCLC.
Indexed on Europe PMC as PubMed record 39521433 (DOI 10.1016/j.jtho.2024.10.024). Its abstract cites the registry id NCT03003962, which is how it was matched to this trial; no figure has been checked by an editor.
This is the paper Europe PMC returns for registry id NCT03003962 with the most citations, so it is the natural first reading for anyone following the PEARL trial. Read the abstract above alongside the trial page and the registry entry; the record was linked automatically and its figures have not been checked by hand.
- Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper.