Effect of Capecitabine Maintenance Therapy Plus Best Supportive Care vs Best Supportive Care Alone on Progression-Free Survival Among Patients With Newly Diagnosed Metastatic Nasopharyngeal Carcinoma Who Had Received Induction Chemotherapy

Abstract

IMPORTANCE Capecitabine maintenance therapy improves survival outcomes in various cancer types, but data are limited on the efficacy and safety of capecitabine maintenance therapy in metastatic nasopharyngeal carcinoma (NPC).OBJECTIVE To investigate the efficacy and safety of capecitabine maintenance therapy in metastatic NPC. DESIGN, SETTING, AND PARTICIPANTSThis randomized phase 3 clinical trial was conducted at Sun Yat-sen University Cancer Center from May 16, 2015, to January 9, 2020, among 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. The final follow-up date was May 30, 2021. All efficacy analyses were conducted in the intention-to-treat population.INTERVENTIONS Eligible patients were randomly assigned (1:1) to receive either capecitabine maintenance therapy (1000 mg/m 2 orally twice daily on days 1-14) every 3 weeks plus best supportive care (BSC) (capecitabine maintenance group) or BSC alone after 4 to 6 cycles of induction chemotherapy.MAIN OUTCOMES AND MEASURES Progression-free survival (PFS). Secondary end points were objective response rate, duration of response, overall survival, and safety. RESULTSThis study included 104 patients (84 men [80.8%]; median age, 47 years [IQR, 38-54 years]), with 52 assigned to the capecitabine maintenance group and 52 assigned to the BSC group. After a median follow-up of 33.8 months (IQR, 22.9-50.7 months), there were 23 events (44.2%) of progression or death in the capecitabine maintenance group and 37 events (71.2%) of progression or death in the BSC group. Median PFS survival was significantly higher in the capecitabine maintenance group (35.9 months [95% CI, 20.5 months-not reached]) than in the BSC group (8.2 months [95% CI, 6.4-10.0 months]), with a hazard ratio of 0.44 (95% CI, 0.26-0.74; P = .002). Higher objective response rates and longer median duration of response were observed in the capecitabine maintenance group (25.0%; 40.0 months) compared with the BSC group (objective response rate, 25.0% [n = 13] vs 11.5% [n = 6]; and median duration of response, 40.0 months [95% CI, not reached-not reached] vs 13.2 months [95% CI, 9.9-16.5 months]). The most common grade 3 or 4 adverse events during maintenance therapy were anemia (6 of 50 [12.0%]), hand-foot syndrome (5 of 50 [10.0%]), nausea and vomiting (3 of 50 [6.0%]), fatigue (2 of 50 [4.0%]), and mucositis (2 of 50 [4.0%]). No deaths in the maintenance group were deemed treatment-related. CONCLUSIONS AND RELEVANCEIn this phase 3 randomized clinical trial, capecitabine maintenance therapy significantly improved PFS for patients with newly diagnosed metastatic NPC who achieved disease control after capecitabine-containing induction chemotherapy. Capecitabine exhibited manageable toxic effects.

Cost-effectiveness analysis of metronomic capecitabine as adjuvant chemotherapy in locoregionally advanced nasopharyngeal carcinoma

“…One study suggested that the first three years after chemoradiotherapy are the highest incidence time of treatment failure ( 23 ). In another study associated with metastatic NPC, the median follow-up duration was 33.8 months, and the results showed that capecitabine maintenance could increase the chances of survival ( 24 ). However, it is still unclear whether the perfect duration of metronomic treatment is one year or not.…”

“…However, it is still unclear whether the perfect duration of metronomic treatment is one year or not. Thus, we used the structural sensitivity analysis and extended the metronomic capecitabine treatment time by three years based on the published studies ( 23 , 24 ). The ICER of metronomic capecitabine versus observation was $12,214.37 per QALY.…”

Comprehensive treatment of recurrent and metastatic nasopharyngeal carcinoma: advances and future directions

“…In 2022, a phase III randomized controlled clinical study on the maintenance treatment of patients with newly diagnosed metastatic NPC with capecitabine was published. 15 In total, 104 patients newly diagnosed with metastatic NPC were included in that study. All patients were 1:1 randomly assigned to the capecitabine maintenance group (1000 mg/m 2 , b.i.d., d1-14, Q3W) or the best supportive treatment group after receiving four to six cycles of paclitaxel, cisplatin, and capecitabine induction chemotherapy.…”

“…Capecitabine maintenance therapy has been shown to improve oncological outcomes in high‐risk subgroups of locally advanced NPC, but its application in metastasis still lacks high‐quality evidence. In 2022, a phase III randomized controlled clinical study on the maintenance treatment of patients with newly diagnosed metastatic NPC with capecitabine was published 15 . In total, 104 patients newly diagnosed with metastatic NPC were included in that study.…”

Cost-effectiveness analysis of capecitabine maintenance therapy plus best supportive care vs. best supportive care alone as first-line treatment of newly diagnosed metastatic nasopharyngeal carcinoma

“…In NPC, moreover, a phase 3 randomized clinical trial (NCT02460419) provided evidence supporting the efficacy of capecitabine maintenance therapy as a first-line treatment for mNPC (26). This trial randomized patients with newly diagnosed mNPC who achieved disease control after 4-6 cycles of induction chemotherapy to receive either capecitabine maintenance therapy plus best supported care (CBSC) or best supported care (BSC) alone (26). Patients in the CBSC group had a significantly higher median PFS survival compared to the BSC group (35.9 vs. 8.2 mo, HR 0.44, 95% CI 0.26-0.74, P = 0.002) (26).…”