Pembrolizumab with or without platinum-based chemotherapy as first-line treatment in advanced NSCLC expressing PD-L1 ≥50%: The PERSEE randomized phase III trial (GFPC 01-2020).
Abstract
Background
Pembrolizumab, alone or combined with platinum-based chemotherapy, is a standard first-line treatment for patients with metastatic non-small-cell lung cancer (NSCLC) without actionable oncogenic alterations and with high programmed death-ligand 1 (PD-L1) expression. We conducted a head-to-head comparison of these two treatment strategies.
Methods
In this multicenter, phase III trial (PERSEE, NCT04547504), adult patients with treatment-naïve stage IV or unresectable stage III NSCLC not amenable to definitive radiotherapy and PD-L1 expression ≥50% were randomly (1:1) assigned to receive pembrolizumab (200 mg every 3 weeks, for up to 35 cycles) or pembrolizumab in combination with four cycles of induction chemotherapy, stratified according to the presence of brain metastases and histologic subtype. Patients with non-squamous histology received cisplatin or carboplatin (AUC 5) plus pemetrexed, followed by pembrolizumab-pemetrexed maintenance; patients with squamous histology received carboplatin (AUC 6) plus paclitaxel, followed by pembrolizumab maintenance. The primary endpoint was progression-free survival (PFS), assessed by blinded central review according to RECIST v1.1. Key secondary endpoints included overall survival (OS), objective response rate, duration of response, and safety.
Results
A total of 321 patients underwent randomization, with 160 assigned to pembrolizumab plus chemotherapy and 161 to pembrolizumab monotherapy. At a median follow-up of 38.7 months, median PFS was significantly longer with combination therapy than with monotherapy (16.1 months [95% CI, 11.0-34.1] vs. 6.9 months [95% CI, 5.5-9.3]; hazard ratio (HR), 0.56; 95% CI, 0.43-0.74; P<0.001). Median OS was 50.2 months versus 29.9 months, respectively (HR, 0.77; 95% CI, 0.56-1.05). Grade ≥3 treatment-related adverse events occurred in 54% and 19% of patients, respectively; grade ≥3 immune-related adverse events occurred in 13% of patients in each group.
Conclusions
Among patients with treatment-naïve advanced NSCLC and high PD-L1 expression, the addition of platinum-based chemotherapy to pembrolizumab significantly prolonged PFS compared with pembrolizumab monotherapy.