Adjuvant sintilimab-capecitabine versus capecitabine alone in locoregionally advanced nasopharyngeal carcinoma with suboptimal response to induction chemotherapy: An open-label, randomized, controlled, phase 2 trial.

LBA6005 Background: Induction chemotherapy (IC) followed by concurrent chemoradiotherapy (CCRT) is the current standard treatment for locoregionally advanced nasopharyngeal carcinoma (LA-NPC); however, patients with a suboptimal response to IC remain at high risk of disease progression. Although adjuvant capecitabine has demonstrated efficacy in high-risk LA-NPC, whether intensifying adjuvant therapy by adding sintilimab, a highly selective, fully humanized monoclonal PD-1 inhibitor to capecitabine, can further improve survival outcomes remains unclear. Methods: This open-label, randomized, phase 2 trial enrolled patients aged 18–70 years with untreated, non-keratinising, stage II–IVA LA-NPC according to the eighth edition of the American Joint Committee on Cancer classification system with suboptimal response to IC, defined as detectable EBV DNA and/or stable or progressive disease after platinum-based IC. After CCRT, all patients were randomly assigned (1:1) to receive either adjuvant sintilimab plus capecitabine or capecitabine alone. Sintilimab (200 mg intravenously) was administered on days 1 and 14 after randomization as a lead-in phase, and then every 3 weeks starting 28 days after CCRT, combined with capecitabine (1000 mg/m² twice daily, days 1–14) for eight cycles; the control group received capecitabine alone on the same schedule starting 28 days after CCRT for eight cycles. The primary endpoint was 2-year progression-free survival (PFS) in the intention-to-treat population. Safety was assessed in all participants who received at least one dose of the assigned treatment. The study was registered at ClinicalTrials.gov (NCT05201859), and patients are under follow-up. Results: One hundred fifty patients were randomised (76 to sintilimab–capecitabine group; 74 to capecitabine group). At a median follow-up of 41 (IQR 35-44) months, the 2-year PFS was 88.2 % in the sintilimab–capecitabine group and 87.8% in the capecitabine group (stratified HR 0.85; 90% CI 0.43–1.70; p=0.77). Grade 3-4 adverse events were reported in 25 (34%) patients in the sintilimab–capecitabine group and in 22 (31%) patients in the capecitabine group; hand-foot syndrome was the most common adverse event in both groups (8% vs. 10%). Immune-related grade 3 myocarditis were occurred in 2 (3%) patients in the sintilimab–capecitabine group. No treatment-related deaths occurred. Conclusion: In patients with LA-NPC who had a suboptimal response to IC, intensification of adjuvant therapy with the addition of sintilimab to capecitabine did not result in a significant improvement in progression-free survival. Future studies are warranted to focus on biomarker-driven patient selection and optimization of immunotherapy sequencing with conventional treatments. Clinical trial information: NCT05201859 .