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Radiotherapy-free option explored in high PD-L1 NSCLC, randomised confirmation still needed

A prospective study reports feasibility of pembrolizumab plus chemotherapy without radiotherapy; the authors say a randomised trial is required before comparison with standard chemoradiotherapy–durvalumab care.

  • Akito Hata, MD; Taira Ninomaru, MD; Hideaki Okada, MD; Yoshihito Kogure, MD; Masahide Oki, MD; Nobuyuki Katakami, MD; et al.

  • October 10, 2025

  • The Lancet Oncology
  • The Lancet Oncology, Volume 26, Issue 11, Pages 1432–1442
  • 10.1016/S1470-2045(25)00462-0

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Evidence before this study

We searched PubMed, Embase, and the Cochrane Library from database inception to Feb 28, 2025, using the terms “locally advanced non-small cell lung cancer”, “PD-L1”, “pembrolizumab”, “chemotherapy”, “radiotherapy”, and “durvalumab”, without language restrictions. We also manually reviewed the reference lists of relevant articles and conference abstracts from major oncology meetings. We included phase 2 and 3 trials evaluating systemic therapy for unresectable, locally advanced non-small-cell lung cancer (NSCLC) with or without radiotherapy. Trials focusing on stage IV cancers or adjuvant settings were excluded. We found no prospective studies evaluating the efficacy of pembrolizumab combined with platinum-based chemotherapy without radiotherapy in patients with unresectable, locally advanced NSCLC and high PD-L1 expression (ie, tumour proportion score [TPS] ≥50%). The standard of care in this setting remains concurrent chemoradiotherapy followed by durvalumab consolidation, as shown in the PACIFIC trial. Although advanced-stage (stage IV) trials have shown durable benefits of pembrolizumab-based regimens in patients with a PD-L1 TPS of 50% or higher, these results have not been prospectively assessed in stage III cancer without radiotherapy.

Added value of this study

To the best of our knowledge, this study is the first prospective investigation of pembrolizumab plus chemotherapy without radiotherapy in patients with unresectable, locally advanced NSCLC and PD-L1 TPS of 50% or higher. Our study highlights the feasibility of this approach and suggests that it might offer a potential alternative treatment option without chemoradiotherapy-induced severe toxicities. These findings contribute to ongoing discussions about optimising treatment strategies for patients with high PD-L1 expression in unresectable, locally advanced NSCLC.

Implications of all the available evidence

Our findings suggest that pembrolizumab plus chemotherapy without radiotherapy could represent a less toxic, potentially curative alternative to chemoradiotherapy followed by durvalumab in patients with unresectable, locally advanced NSCLC with PD-L1 TPS of 50% or higher. A randomised controlled trial is warranted to confirm the efficacy of this radiotherapy-free approach compared with the current standard of care in this patient population.

Source: The Lancet Oncology

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