Pembrolizumab monotherapy for mNSCLC: 10-year data

In this video, Prof Els Wauters, respiratory oncologist at the University Hospitals Leuven and Prof Sebahat Ocak, pulmonologist at the CHU UCL Namur discuss the long-term follow-up data from the different pembrolizumab monotherapy trials in advanced non–small cell lung cancer (NSCLC) as presented at ESMO 2025. 

Four trials evaluated pembrolizumab monotherapy in patients with metastatic NSCLC. KEYNOTE-001, a first-in-human Phase 1 study, included previously treated patients with any PD-L1 expression and demonstrated encouraging long-term survival with pembrolizumab. KEYNOTE-010, was a phase 2/3 trial comparing pembrolizumab to docetaxel in the second-line treatment of mNSCLC with a PD-L1 expression ≥1%. Also this trial demonstrated a significant improvement in overall survival, particularly in high PD-L1 expressors. The landmark phase 3 KEYNOTE-024 trial established pembrolizumab as standard of care in the first-line treatment for mNSCLC patients with a high level of PD-L1 expression (≥50%), demonstrating superiority over platinum-doublet chemotherapy. Finally, KEYNOTE-042 expanded this question to the ≥1% PD-L1 population, but had a more modest impact than KEYNOTE-024.

At ESMO 2020, 5-year follow-up of KEYNOTE-024 showed that 31% of patients were still alive in the pembrolizumab arm, which was twice as much as in the control arm. The newly presented long-term update of this study and the other monotherapy studies conform and extend these observations. In KEYNOTE-010, the 10-year OS rate was 9% with pembrolizumab vs 2% with chemotherapy in the PD-L1 ≥1% group, rising to 15% vs. 3% in the high expressors. In KEYNOTE-024, with 8 years of follow-up, OS was 24% with pembrolizumab as compared to 13% with chemotherapy. KEYNOTE-024 results on lung cancer–specific survival were even more striking with 8-year rates of 33.7% and 23.2% for pembrolizumab and chemotherapy, respectively.

Progression-free survival (PFS) rates were lower across the four studies but still indicate a durable effect in a subgroup of patients. In KEYNOTE-010, 10-year PFS rates were 6% vs. 2% in the PD-L1 ≥1% subgroup and 11% vs. 1% in high PD-L1 expressors (PD-L1 ≥50%). In KEYNOTE-024, the 8-year PFS rate with pembrolizumab mounted to 13% as compared to only 3% in the chemotherapy arm.

For Prof Wauters & Prof Ocak, these data underscore the transformative impact of pembrolizumab monotherapy for mNSCLC patients expressing high levels of PD-L1 NSCLC. The sustained survival plateaus suggest potential long-term remission for a proportion of patients. However, the patients remaining free of disease progression at 8 years is still only a minority, emphasizing the continued need for new therapies, rational combinations, and biomarker-driven approaches to overcome resistance and further improve survival outcomes.