1445P - A randomized phase III trial on Pembrolizumab Alone versUs pembrolizumab-chemotherapy in first LInE NSCLC (PAULIEN), results of the interim analysis

Background

To date, first-line pembrolizumab monotherapy (PEM) has not been compared to pembrolizumab + chemotherapy (PEM/CT) in metastatic non-small cell lung cancer (NSCLC) with PD-L1 TPS ≥50%. However, the regimen that provides the highest response rate, crucial for when a tumor response is urgently needed, is unknown. Here, we report the interim results of the PAULIEN study (NTR 8896), aiming to identify the regimen (PEM or PEM/CT) with the highest response rate.

Methods

This open label, phase 3, multicenter trial aimed to randomize (1:1) 84 patients with untreated metastatic NSCLC with PD-L1 TPS ≥50% and a high tumor burden to receive PEM (200mg fixed, 3 or 6 weekly) or PEM (200mg fixed, 3 weekly) + platinum-based chemo-doublets with either pemetrexed or paclitaxel. Pemetrexed and PEM were continued as maintenance therapy. Patients in the PEM arm received CT after progressive disease. Stratification factors included age, performance status, T-stage and histology. Co-primary endpoints were objective response rate (ORR) and disease control rate (DCR) at week 6 and 12 per RECIST v1.1. Secondary endpoints included progression-free survival, overall survival and safety. A planned interim analysis was performed (data cut-off March 1st, 2023).

Results

50 patients were randomized to PEM (n=19) and PEM/CT (n=31). Baseline characteristics were well balanced between arms. 42 patients were radiologically evaluable of whom 17 patients received PEM and 25 patients PEM/CT. The PEM arm demonstrated an ORR at week 6 of 38% vs. 44% in the PEM/CT arm (p=0.68) and a DCR of 88% vs. 88% (p=1.0). At week 12, the PEM arm demonstrated an ORR of 74% vs. 68% in the PEM/CT arm (p=1.0) and a DCR of 93% vs. 91% (p=1.0), respectively. The incidence of grade 3-4 treatment-related adverse events was 28% (PEM) vs. 52% (PEM/CT). No treatment-related deaths occurred.

Conclusions

In this interim analysis, the tumor response rate with first-line PEM alone was comparable to that of PEM/CT in metastatic NSCLC patients with PD-L1 TPS ≥50%,. No new safety signals were observed. More data is needed to explore subgroups that may still benefit from adding chemo to PEM in this population.

Clinical trial identification

NTR8896.

Editorial acknowledgement

Legal entity responsible for the study

Department of Pulmonary Medicine, Amsterdam University Medical Centers, location VU Medical Center.

Funding

Paulien van Deutekom Foundation.

Disclosure

All authors have declared no conflicts of interest.