Recurrent or metastatic nasopharyngeal carcinoma (RM-NPC) is a distinct head and neck malignancy strongly linked to Epstein-Barr virus (EBV) infection and endemic in East and Southeast Asia. Historically, outcomes have been poor in this setting despite platinum-based chemotherapy. Programmed cell death-1 (PD-1) inhibitors combined with chemotherapy have become the standard first-line strategy based on superior progression-free survival (PFS) in multiple randomised trials. However, long-term overall survival (OS) data have been limited — until now.
The CAPTAIN-1st trial enrolled 263 patients with treatment-naive RM-NPC across 28 hospitals in China. Participants were randomized 1:1 to receive either camrelizumab plus gemcitabine/cisplatin or placebo plus chemotherapy. After induction cycles, patients continued maintenance therapy until progression, toxicity, or up to two years. Median follow-up exceeded five years.
CLINICAL SUMMARY
What was examined
A prespecified secondary analysis of the phase-3 CAPTAIN-1st trial comparing camrelizumab plus gemcitabine/cisplatin versus chemotherapy alone as first-line treatment of recurrent or metastatic nasopharyngeal carcinoma (RM-NPC), with a focus on five-year overall survival (OS) outcomes.
Key findings:
- Adding camrelizumab to standard chemotherapy significantly improved 5-year OS compared with chemotherapy alone (37.8% vs 24.2%).
- Median OS was longer with camrelizumab (34.5 months vs 26.6 months).
- Rapid clearance of plasma Epstein-Barr virus (EBV) DNA was associated with particularly favourable long-term outcomes.
Clinical implications:
- This provides the first 5-year OS evidence supporting PD-1 blockade with chemotherapy as the standard first-line treatment in RM-NPC.
- EBV DNA clearance may serve as a valuable prognostic biomarker for identifying patients most likely to benefit long-term.
- Long-term survival plateaus indicate durable benefit in a subset of patients, reinforcing current treatment paradigms.
With approximately 63 months of follow-up, the addition of camrelizumab provided a statistically significant and clinically meaningful OS benefit:
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Median OS: 34.5 months with camrelizumab vs 26.6 months with chemotherapy alone (HR, 0.74).
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Five-year OS rate: 37.8% vs 24.2%, an absolute improvement of 13.6% favoring camrelizumab.
These outcomes remain significant after adjustment for age imbalances between arms.
Interestingly, rapid clearance of plasma EBV DNA — a virus associated with NPC tumorigenesis — emerged as a strong prognostic marker of long-term survival among patients treated with camrelizumab.
This analysis delivers the first robust 5-year survival benchmark for a PD-1–based chemoimmunotherapy regimen in RM-NPC, marking a meaningful shift in expectations for long-term outcomes in this traditionally poor-prognosis disease. The durable survival plateau observed in the camrelizumab arm suggests that a proportion of patients achieve sustained benefit beyond what historical chemotherapy alone has delivered.
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The correlation between EBV DNA clearance and survival also highlights the potential utility of viral biomarkers to stratify risk and personalize follow-up strategies, although further validation is needed.
Given the endemic setting of the trial (East Asian populations with predominantly non-keratinizing histology), whether these results generalize to non-endemic regions warrants further investigation. Additionally, survival benefits associated with longer maintenance therapy may be influenced by survivorship bias rather than causality.
The CAPTAIN-1st five-year analysis affirms that camrelizumab plus chemotherapy significantly improves long-term survival in patients with RM-NPC, supporting its role as the first-line standard of care and establishing a new benchmark for durable outcomes in this challenging disease setting.
Paper: Huang Y, et al. Five-Year Outcome of Camrelizumab Plus Chemotherapy in Recurrent or Metastatic Nasopharyngeal Carcinoma: A Secondary Analysis of the CAPTAIN-1st Randomized Clinical Trial. JAMA Oncol. Published online January 29, 2026. doi:10.1001/jamaoncol.2025.6245 Access online here.
