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)
In brief
Adding chemotherapy to pembrolizumab extended median progression-free survival to 16.1 vs 6.9 months
In a randomized trial of patients with advanced non-small-cell lung cancer and high PD-L1 expression, adding platinum-based chemotherapy more than doubled median time before disease progression, from 6.9 to 16.1 months. Median overall survival was 50.2 months with combination treatment and 29.9 months with pembrolizumab alone, but the trial did not establish a survival benefit; severe treatment-related side effects were also more common with chemotherapy.
- Journal
- Annals of oncology : official journal of the European Society for Medical Oncology (Q1)
- Published
- 25 October 2026
- Study design
- Randomized controlled trial
- Evidence level
- Level 1, High (CEBM 1b)
- Authors
- Renaud Descourt, Alice Mogenet, Maelys Consigny, Marie Bernardi, Romain Corre, Olivier Bylicki, et al.
- PMID
- 42927854
- DOI
- 10.1016/j.annonc.2026.10.108
Why clinicians should know about it
- Picked for Oncology and Radiation Oncology (top studies of the week, 1 November 2026): Phase III trial compares immunotherapy alone versus chemo-immunotherapy in advanced
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.
Abstract as published, via PubMed.
For healthcare professionals. The summary is generated by AI from the published abstract, and the evidence level is assigned automatically from the study design on the Oxford CEBM hierarchy. Neither is medical advice. Read the full paper before changing practice.