Adjuvant PD-1 Blockade With Camrelizumab for Nasopharyngeal Carcinoma: The DIPPER Randomized Clinical Trial

Abstract

Importance: Approximately 20% to 30% of patients with locoregionally advanced nasopharyngeal carcinoma (NPC) experience disease relapse despite definitive chemoradiotherapy. The programmed cell death 1 (PD-1) blockade camrelizumab has demonstrated considerable value in recurrent or metastatic NPC, while its role in locoregionally advanced NPC is unclear.

Objective: To evaluate the efficacy and safety of adjuvant camrelizumab for patients with locoregionally advanced NPC.

Design, setting, and participants: Randomized, open-label, multicenter, phase 3 clinical trial conducted from August 2018 to November 2021 at 11 centers in China and enrolling 450 patients with T4N1M0 or T1-4N2-3M0 NPC who had completed induction-concurrent chemoradiotherapy. The final date of follow-up was March 20, 2024.

Interventions: Patients were randomized (1:1) to receive adjuvant camrelizumab (200 mg intravenously once every 3 weeks for 12 cycles; n = 226) or observation (standard therapy group; n = 224).

Main outcomes and measures: The primary end point was event-free survival (freedom from distant metastasis, locoregional relapse, or death due to any cause). Secondary end points included distant metastasis-free survival, locoregional relapse-free survival, overall survival, safety, and health-related quality of life.

Results: Among the 450 participants (mean age, 45 [SD, 10] years; 24% women), after a median follow-up of 39 (IQR, 33-50) months, the camrelizumab group had a 3-year event-free survival rate of 86.9%, whereas the standard therapy group had a rate of 77.3% (stratified hazard ratio, 0.56; 95% CI, 0.36-0.89; P = .01). Grade 3 or 4 adverse events were reported in 23 patients (11.2%) in the camrelizumab and 7 (3.2%) in the standard therapy group. Reactive capillary endothelial proliferation was the most common adverse event related to camrelizumab, occurring in 85.8% of patients at grade 1 or 2, while 2% of patients had grade 3 or 4 events. There was no significant deterioration in quality of life associated with camrelizumab treatment.

Conclusions and relevance: Adjuvant PD-1 blockade with camrelizumab significantly improved event-free survival with manageable toxicities, highlighting its potential role in the management of locoregionally advanced NPC.

Trial registration: ClinicalTrials.gov Identifier: NCT03427827.

Figure 1.. Flow of Participants Through the DIPPER Trial

^aPatients were required to have completed gemcitabine and cisplatin induction chemotherapy plus concurrent chemoradiotherapy before enrollment. ^bRandomization was stratified by trial center and disease stage. ^cThese 19 patients did not receive any adjuvant treatment unless disease progression occurred.

Figure 2.. Kaplan-Meier Analysis of Survival Stratified by Randomization Group

The stratified log-rank test was used to calculate P values. All stratified analyses used the same stratification factors that were used for randomization (trial center and disease stage). Median observation times were as follows: any disease relapse or death, 37 (IQR, 32-46) months; distant metastasis or death, 37 (IQR, 32-46) months; locoregional relapse or death, 37 (IQR, 32-46) months; and death, 39 (IQR, 33-50) months.