In brief
- PERSEE randomised 321 patients with untreated advanced NSCLC and PD-L1 expression of 50% or more to pembrolizumab alone or pembrolizumab with four cycles of platinum-based chemotherapy.
- Median progression-free survival by blinded central review was 16.1 months with the combination and 6.9 months with pembrolizumab alone (hazard ratio 0.56; P<0.001).
- Median overall survival was 50.2 months against 29.9 months, with a hazard ratio of 0.77 whose confidence interval crossed 1.
- Grade 3 or higher treatment-related adverse events occurred in 54% of patients given the combination and 19% of those given monotherapy.
- Grade 3 or higher immune-related adverse events occurred in 13% of patients in each group.
Study at a glance
- Trial: PERSEE (GFPC 01-2020), multicentre, randomised 1:1, phase III
- Population: 321 adults with untreated stage IV, or unresectable stage III NSCLC not amenable to definitive radiotherapy, PD-L1 50% or more
- Treatment: pembrolizumab 200 mg every 3 weeks for up to 35 cycles (n=161), or the same with four cycles of induction platinum doublet (n=160)
- Stratification: brain metastases and histologic subtype
- Primary endpoint: PFS by blinded central review (RECIST v1.1)
- Follow-up: median 38.7 months
- PFS: 16.1 vs 6.9 months; HR 0.56; P<0.001
- Overall survival: 50.2 vs 29.9 months; HR 0.77, not statistically significant
- Safety: grade 3 or higher treatment-related adverse events 54% vs 19%
A head-to-head test of two accepted first-line options
For patients whose tumours carry no actionable oncogenic alteration and have PD-L1 expression of 50% or more, both pembrolizumab alone and pembrolizumab with chemotherapy are standard first-line choices. PERSEE was designed as a head-to-head randomised comparison of the two.
PERSEE assigned the chemotherapy by histology. Patients with non-squamous disease received cisplatin or carboplatin (AUC 5) with pemetrexed, followed by pembrolizumab and pemetrexed maintenance. Patients with squamous disease received carboplatin (AUC 6) with paclitaxel, followed by pembrolizumab maintenance.
Median PFS of 16.1 months with the combination, against 6.9 months
After a median follow-up of 38.7 months, the 160 patients given the combination had a 44% lower risk of progression or death than the 161 given pembrolizumab alone (hazard ratio 0.56). Progression was judged by blinded central review rather than by the treating investigators.
The trial met its primary endpoint. The abstract does not give response rates or duration of response, both of which were key secondary endpoints, and it reports no results by histology or by brain metastases at baseline, although randomisation was stratified on both.
An overall survival gap of 20 months that did not reach significance
Median overall survival was 50.2 months with the combination and 29.9 months with monotherapy. The hazard ratio of 0.77 had a 95% confidence interval of 0.56 to 1.05, so the trial cannot exclude the absence of a survival difference. Overall survival was a key secondary endpoint, and the abstract gives no figures for treatment received after progression in either arm.
“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.”Descourt et al., Annals of Oncology (2026)
Nearly three times the rate of severe treatment-related toxicity
Grade 3 or higher treatment-related adverse events occurred in 54% of the combination group and 19% of the monotherapy group. Grade 3 or higher immune-related adverse events were equally frequent, at 13% in each arm, so the difference between the groups lay in toxicity outside the immune-related category.
The PFS gain therefore came with more severe treatment-related toxicity, and the survival data do not show a statistically significant difference to set against it. Quality-of-life results, which would help weigh the two, are not in the abstract.
Sources
- Annals of Oncology. 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) (2026-10-01). doi.org
Featuring Lung Summit faculty
This study was co-authored by Lung Summit faculty Maurice Pérol.
This article was produced independently by the Lung Summit editorial team, without industry funding or input.
