Approximately a quarter of patients with nasopharyngeal cancer (NPC) require systemic therapy because of de novo metastatic disease or recurrence after treatment of non-metastatic disease. Until recently, the standard of care for patients with recurrent or metastatic (R/M) NPC was platinum-based chemotherapy. Although responses to chemotherapy are high, they are rather short-lived, and strategies to improve treatment outcomes have been investigated, including the addition of anti-PD-1 immunotherapy and maintenance capecitabine.

The efficacy of maintenance therapy with capecitabine has been proven in some other cancer types, as well as in locoregionally advanced NPC. However, the benefit of capecitabine maintenance for patients with metastatic NPC is uncertain. This was evaluated in a recently published phase III trial conducted at Sun Yat-sen University Cancer Center in China. The study enrolled 104 patients with newly diagnosed metastatic NPC who had achieved disease control after 4 to 6 cycles of induction chemotherapy with paclitaxel, cisplatin, and capecitabine. Patients were then randomized to receive either capecitabine maintenance (1000 mg/m² orally twice daily for 2 out of every 3 weeks for up to 2 years) plus best supportive care (BSC), or BSC alone. At a median follow-up of 33.8 months, the median progression-free survival (PFS) was substantially improved with capecitabine maintenance compared with BSC alone (35.9 vs. 8.2 months; hazard ratio [HR], 0.44; P = 0.002). In addition, investigators observed higher objective response rates with the capecitabine maintenance (25.0%) compared with the BSC (11.5%). Similarly, the median duration of response was longer in patients receiving capecitabine maintenance (40.0 vs. 13.2 months; HR, 0.44; P = 0.002). No significant difference was observed for overall survival (OS; HR, 0.59; P = 0.13). However, after excluding patients who received crossover treatment, a significant OS benefit was observed in favor of capecitabine maintenance. Importantly, occurrence of grade 3–4 toxicities with capecitabine maintenance were low and manageable; most frequent were anemia (12%) and hand–foot syndrome (10%). Of note, the compliance rate for capecitabine maintenance was very high; treatment discontinuation was only required in one patient and dose modification in 6 patients.

Based on the results of this study, and given that the duration of response to initial therapy in most patients with metastatic NPC is short, the authors believe that maintenance capecitabine could be a user-friendly, easily accessible, and cost-effective strategy. Based on recent success with immunotherapy (camrelizumab and toripalimab) in metastatic NPC, they suggest further investigation of the efficacy and safety of capecitabine maintenance in combination with immune checkpoint inhibitors. In an accompanying editorial, the authors note that the results of this trial, and others reported in 2021, exemplify the progress made in the management of R/M NPC. They applauded the authors for completing the trial, which provides another life-prolonging treatment option. However, they highlighted the need for comparative trials of maintenance capecitabine and immunotherapy, evaluation of the maintenance capecitabine dose and an investigation of the use of existing (e.g. Epstein–Barr virus DNA) and new biomarkers to guide treatment duration.

Reference:
Liu GY, et al. JAMA Oncol. 2022 Feb 2 [Online ahead of print].