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

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.