Concurrent Versus Sequential PD-1 Blockade With Locoregional Radiotherapy After Chemoimmunotherapy in De Novo Metastatic Nasopharyngeal Carcinoma: A Landmark Analysis.

Authors

Linfang Wu, Jiarui He, Zhenhua Zhou, Renhao Luo, Cong Li, Linquan Tang, Haiqiang Mai, Liting Liu

Published in

Oral oncology. Volume 182. Pages 108164. Oct 03, 2026. Epub Oct 03, 2026.

Abstract

Chemoimmunotherapy followed by consolidative locoregional radiotherapy has increasingly been used for selected patients with de novo metastatic nasopharyngeal carcinoma (dmNPC). However, whether PD-1 blockade should be continued concurrently during locoregional radiotherapy (LRRT) remains uncertain.
We retrospectively analyzed 238 patients with de novo metastatic nasopharyngeal carcinoma who received platinum-based chemotherapy plus anti-PD-1 therapy followed by definitive locoregional radiotherapy. A 12-month landmark analysis was performed to reduce immortal time bias, and inverse probability of treatment weighting was used to balance baseline and treatment-related characteristics. Recursive partitioning analysis incorporating disease burden, pretreatment lactate dehydrogenase, post-chemoimmunotherapy Epstein-Barr virus DNA clearance, and radiological response was used for risk stratification. Longitudinal absolute lymphocyte counts were evaluated after radiotherapy.
Among 238 patients, 185 received concurrent PD-1 blockade during locoregional radiotherapy and 53 did not. After weighting and landmark adjustment, concurrent PD-1 blockade was associated with inferior progression-free survival (PFS) (weighted hazard ratio, 3.189; 95% CI, 1.352-7.524; P=0.008). Distant metastasis-free survival was also inferior in the concurrent group, whereas locoregional recurrence-free survival was similar between groups. Among the four observed treatment patterns, the sandwich strategy, defined as chemoimmunotherapy followed by LRRT without concurrent PD-1 blockade and with subsequent maintenance immunotherapy, showed the most favorable outcomes. In the landmark-adjusted comparison restricted to the full-course and sandwich strategies, the sandwich strategy remained associated with superior PFS (hazard ratio, 0.254; 95% CI, 0.078-0.821; P=0.022). Exploratory subgroup analyses suggested a less favorable outcome pattern with concurrent PD-1 blockade among high-risk patients, although individual subgroup sizes were limited. Persistent lymphopenia at 3 months after radiotherapy was associated with poor outcomes, particularly among patients receiving concurrent PD-1 blockade.
In conclusion, among patients with dmNPC treated with first-line chemoimmunotherapy followed by definitive LRRT, concurrent PD-1 blockade during LRRT was not associated with improved survival outcomes and was linked to inferior PFS and DMFS in an IPTW-adjusted landmark analysis. Exploratory analyses suggested potential heterogeneity according to baseline risk and post-radiotherapy immune recovery, but these findings were limited by small subgroup sizes. Prospective studies are warranted to define the optimal sequencing of PD-1 blockade and LRRT.

PMID:
42828792
Bibliographic data and abstract were imported from PubMed on 04 Oct 2026.

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