CAPTAIN-1st provides pivotal 5-year evidence supporting PD-1–based chemoimmunotherapy in RM-NPC.A secondary analysis of the phase III CAPTAIN-1st trial shows a significant overall survival (OS) benefit when camrelizumab is added to gemcitabine and cisplatin (GC) for the first-line (1L) treatment of recurrent or metastatic nasopharyngeal carcinoma (RM-NPC).
After a median follow-up of 63 months, the median OS was longer in the camrelizumab than in the placebo group (34.5 vs 26.6 months; stratified hazard ratio [HR], 0.74; two-sided p=0.047). Adjustment for age imbalance yielded an HR of 0.65 (p=0.01). [JAMA Oncol 2026;12:295-302]
The 5-year OS rates in the camrelizumab and placebo groups were 37.8 percent vs 24.2 percent, respectively, reflecting an absolute difference of 13.6 percent (p=0.02) in favour of camrelizumab. The OS benefits were generally consistent across subgroups.
“The OS rate [with camrelizumab suggests] that about one-third of patients achieved sustained long-term survival. [This] provides pivotal 5-year evidence supporting PD-1–based chemoimmunotherapy in RM-NPC,” the investigators said.
Over three-quarters (77.5 percent) of camrelizumab-treated patients achieved rapid Epstein-Barr virus (EBV) DNA clearance, defined as a change from positive at baseline to negative within the first three treatment cycles; two-thirds did so in the placebo group.
In the camrelizumab group, participants who achieved rapid clearance had a markedly longer median OS (50.5 vs 27.8 months; HR, 0.32; p<0.001) and a sixfold higher 5-year OS rate (46.8 percent vs 7.5 percent) than those who did not.
Dynamic changes in plasma EBV DNA are tied to clinical outcomes after chemo and radiotherapy, with evidence supporting their prognostic value in immunotherapy. [Clin Cancer Res 2021;27:2827-2836; Lancet Oncol 2021;22:1162-1174; J Clin Oncol 2021;39:704-712; JAMA Netw Open 2022;5:e220587] “Our extended follow-up provides the first 5-year evidence that rapid plasma EBV DNA clearance is a robust prognostic biomarker [of long-term survival],” the researchers said.
“[Hence,] longitudinal monitoring of plasma EBV DNA should be incorporated into clinical practice to guide individualized treatment,” they added. Patients who fail to achieve rapid clearance may require alternative treatments, such as novel immune checkpoint inhibitors or antibody-drug conjugates. [Nat Med 2025;31:1949-1957; Lancet Oncol 2024;25:901-911; J Hematol Oncol 2025;18:15]
NPC prevalence is highest in East and Southeast Asia, and EBV infection is largely associated with NPC development in these endemic regions. [Lancet 2019;394:64-80]
In CAPTAIN-1st, all participants were Asian (n=263; mean age 49 years, 82.9 percent men). They were randomized 1:1 to receive IV camrelizumab 200 mg or placebo with 4–6 cycles of GC*, followed by maintenance with camrelizumab or placebo Q3W until disease progression, unacceptable toxicities, or completion of 2 years of treatment. Placebo recipients, upon progression, were not permitted to cross over to the camrelizumab group.
Five-year survival has long been recognized as a benchmark of cancer treatment effectiveness. [Lancet 2018;391:1023-1075] “In the era of immunotherapy, long-term survival is particularly meaningful because survival plateaus have been observed in several malignant diseases,” the researchers noted.
For RM-NPC, PD-(L)1 inhibitors + chemo have been established as 1L standard of care, but 5-year survival outcomes have not been reported. [JAMA 2023;330:1961-1970; Ann Oncol 2024;35:S1554-SS2555]
“These findings provide the first 5-year evidence to inform clinical practice on PD-1–based chemoimmunotherapy in RM-NPC, supporting camrelizumab + chemo as the standard 1L treatment and establishing a new benchmark for long-term survival in this population,” the researchers concluded.
Of note, OS was a key secondary endpoint, but no multiplicity adjustment was conducted for the OS analysis, they pointed out. “Nonetheless, the OS results still provided meaningful evidence of the long-term survival benefits of camrelizumab + chemo as 1L treatment of RM-NPC.”
As all participants were from NPC-endemic East-Asian regions, the researchers called for further investigation to validate the benefits of camrelizumab + chemo in nonendemic regions.