A Multicentre Phase II Study of Trifluridine/Tipiracil in Recurrent/Metastatic Platinum-Resistant Nasopharyngeal...

Therapeutic options beyond platinum, gemcitabine, and immunotherapy in recurrent/metastatic (R/M) nasopharyngeal carcinoma (NPC) remain limited. Median overall survival (OS) for R/M disease is 20 months. This study evaluated the efficacy and safety of trifluridine/tipiracil (FTD/TPI) in platinum-resistant R/M NPC.

In this single-arm, phase II study, patients received oral FTD/TPI at 35 mg/m2 twice daily on days 1 to 5 and 8 to 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.

Thirty-five patients were enrolled. The median age was 56 years with a median of 2 prior lines of systemic therapy (range, 1-7). Forty five percent patients had prior fluoropyrimidine. The DCR at 12 weeks was 57.1% [95% confidence interval (CI), 39.4%-73.7%], and the ORR was 22.9% (95% CI, 10.4-40.1). The DCR was comparable with and without fluoropyrimidine exposure (55.6% vs. 58.8%). The median PFS was 6.5 months, and the 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 because of symptomatic anemia. Grades 3 to 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 nonresponders, warranting further validation in larger cohorts.

FTD/TPI demonstrated a manageable safety profile and encouraging antitumor activity. It is a convenient oral alternative to intravenous chemotherapy.