Final Analysis of PEARL Study Evaluates Durvalumab Versus Chemotherapy as First-Line Treatment for NSCLC

Durvalumab does not significantly improve overall survival (OS) compared to chemotherapy when administered as first-line treatment for patients with metastatic non-small cell lung cancer (mNSCLC) and PD-L1 tumor cell membrane expression status ≥25% (PD-L1 TC ≥25%), according to findings from the PEARL study.

A team of researchers from China conducted a final analysis of the study comparing first-line durvalumab monotherapy with chemotherapy in patients with mNSCLC.

The phase III study evaluated 669 patients with previously untreated stage IV mNSCLC across two populations. The first group included patients with PD-L1 TC ≥25% and the second group included patients with PD-L1 TC ≥25% and low risk of early mortality (LREM).

All patients were randomly assigned to receive either 20 mg/kg of durvalumab every four weeks or chemotherapy every three weeks for four to six cycles. The primary endpoint for both groups was overall survival (OS).

The study found that “durvalumab was associated with a numerical reduction in the risk of death versus chemotherapy in the PD-L1 TC ≥25% population.” The OS hazard ratio (HR) was 0.84 (95% CI, 0.71, 0.99, P=.037). In the same population, the median OS was 14.6 months (95% CI: 12.2, 16.9) for durvalumab and 12.8 months (95% CI: 10.1, 14.7) for chemotherapy.

Among patients in the PD-L1 TC ≥25% LREM population, “the OS HR for durvalumab versus chemotherapy was 0.96 (95% CI, 0.79, 1.15; P=.628).” For durvalumab, the median OS was 14.6 months (95% CI: 12.6, 17.2) compared to 15 months for chemotherapy (95% CI: 13.1, 16.8).

According to the study authors, the incidence of a grade 3 or 4 treatment-related adverse event was 15.5% for durvalumab in the safety population and 45.9% for chemotherapy.

While durvalumab was not found to improve OS compared to chemotherapy when administered as first-line treatment for patients with mNSCLC and PD-L1 TC ≥25%, the researchers concluded that “the numerical improvement in OS was consistent with previous studies of first-line immune checkpoint inhibitor monotherapy in patients with mNSCLC.”

Source: Journal of Thoracic Oncology