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: A Phase 3 Randomized Clinical Trial.

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 PARTICIPANTS:

This 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/m2 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.

RESULTS:

This 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 RELEVANCE:

In 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.

TRIAL REGISTRATION:

ClinicalTrials.gov Identifier: NCT02460419.

• Authors: Guo-Ying Liu, Wang-Zhong Li, De-Shen Wang, Hu Liang, Xing Lv, Yan-Fang Ye, Chong Zhao, Liang-Ru Ke, Shu-Hui Lv, Nian Lu, Wei-Xin Bei, Zhuo-Chen Cai, Xi Chen, Chi-Xiong Liang, Xiang Guo, Wei-Xiong Xia, Yan-Qun Xiang
• Journal: JAMA oncology (JAMA Oncol) Vol. 8 Issue 4 Pg. 553-561 (04 01 2022) ISSN: 2374-2445 [Electronic] United States
• PMID: 35175316 (Publication Type: Clinical Trial, Phase III, Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Capecitabine

Topics

• Antineoplastic Combined Chemotherapy Protocols (adverse effects)
• Capecitabine (adverse effects)
• Female
• Humans
• Male
• Middle Aged
• Nasopharyngeal Carcinoma (drug therapy)
• Nasopharyngeal Neoplasms (drug therapy)
• Progression-Free Survival