A multicentre phase 2 study of trifluridine/tipiracil in recurrent/metastatic platinum resistant nasopharyngeal carcinomas

Purpose: Therapeutic options beyond platinum, gemcitabine and immunotherapy in r/m NPC remain limited. Median overall survival for R/M disease is 20 months. This study evaluated the efficacy and safety of FTD/TPI in platinum-resistant R/M NPC. Experimental design: In this single-arm, phase II study, patients received oral FTD/TPI at 35 mg/m² twice daily on days 1–5 and 8–12 of each 28-day cycle. The primary endpoint was disease control rate (DCR) at 12 weeks. Secondary endpoints included progression-free survival (PFS), overall response rate (ORR) and safety. Results: Thirty-five patients were enrolled. Median age was 56 years with a median of 2 prior lines of systemic therapy (range, 1–7). 45% had prior fluoropyrimidine. DCR at 12 weeks was 57.1% (95% CI: 39.4%-73.7%) and the ORR was 22.9% (95% CI: 10.4-40.1). DCR was comparable with and without fluoropyrimidine exposure (55.6% vs 58.8%). Median PFS was 6.5 months, and median OS was 13.1 months. Treatment-emergent adverse events were predominantly hematologic, including ≥ Grade 3 neutropenia (43%), anemia (26%), and thrombocytopenia (9%), with grade ≥3 events largely hematologic. Dose modifications were required in 60%, most commonly due to neutropenia, manageable with dose reduction. One patient discontinued treatment due to symptomatic anemia. G3–4 neutropenia was significantly associated with improved ORR (p<0.001). Exploratory plasma proteomic analyses suggested potential differences in baseline and on-treatment protein expression between responders and non-responders, warranting further validation in larger cohorts. Conclusion: FTD/TPI demonstrated a manageable safety profile and encouraging antitumor activity. It is a convenient oral alternative to intravenous chemotherapy.