Maintenance therapy improves the survival outcomes of patients with metastatic nasopharyngeal carcinoma responding to first-line chemotherapy: a multicentre, randomized controlled clinical study

Ying Lu; Haixin Huang; Hui Yang; Xiaohua Hu; Meilian Liu; Changjie Huang; Xianbin Feng; Xishan Chen; Zhou Jiang

doi:10.1007/s00432-022-04341-2

Maintenance therapy improves the survival outcomes of patients with metastatic nasopharyngeal carcinoma responding to first-line chemotherapy: a multicentre, randomized controlled clinical study

J Cancer Res Clin Oncol. 2023 Jul;149(8):4327-4338. doi: 10.1007/s00432-022-04341-2. Epub 2022 Sep 8.

Authors

Ying Lu¹, Haixin Huang², Hui Yang¹, Xiaohua Hu³, Meilian Liu⁴, Changjie Huang⁵, Xianbin Feng⁶, Xishan Chen¹, Zhou Jiang¹

Affiliations

¹ Department of Oncology, The Fourth Affiliated Hospital of Guangxi Medical University, No.1 Liushi Road, Liuzhou, 545000, Guangxi, China.
² Department of Oncology, The Fourth Affiliated Hospital of Guangxi Medical University, No.1 Liushi Road, Liuzhou, 545000, Guangxi, China. 13507726193@163.com.
³ Department of Oncology, The First Affiliated Hospital of Guangxi Medical University, Nanning, 530000, China.
⁴ Department of Oncology, Affiliated Hospital of Guilin Medical College, Guilin, 541000, China.
⁵ Department of Oncology, The Third Affiliated Hospital of Guangxi Medical University, Nanning, 530000, China.
⁶ Department of Oncology, Liuzhou Hospital of Traditional Chinese Medicine, Liuzhou, 545000, China.

Abstract

Purpose: To explore the safety and role of tegafur/gimeracil/oteracil (S1) maintenance therapy (MT) in metastatic nasopharyngeal carcinoma (NPC) patients after response to first-line chemotherapy and to assess outcome-associated biomarkers.

Methods: This was a multicentre, open-label, randomized controlled study involving metastatic NPC patients recruited (from May 2015 to May 2019) at five hospitals in China. The participants were randomized to S1-MT (receiving S1 MT until disease progression or intolerance) or non-MT (followed up until disease progression) groups. The primary endpoint was the progression-free survival (PFS). The secondary endpoints were the overall survival (OS), the correlation between EBV-DNA, serum amyloid A (SAA) status, and outcomes after the first-line chemotherapy, and safety.

Results: The median follow-up was 24.3 months; 88 and 95 participants were evaluable in the S1-MT and non-MT groups, respectively. Compared with non-MT, S1-MT prolonged PFS (16.9 vs. 9.3 months, P < 0.001) and OS (33.6 vs. 20.6 months, P < 0.001). Regardless of their EBV-DNA status after first-line chemotherapy, participants were able to benefit from S1 MT, but EBV-DNA-positive participants benefited more significantly (PFS: HR = 0.600, 95% CI = 0.373-0.965, P = 0.035; OS: HR = 0.393, 95% CI = 0.227-0.681, P = 0.001). MT only improved PFS and OS in patients with an SAA decline after first-line chemotherapy (PFS: HR = 0.570, 95% CI = 0.350-0.919, P = 0.021; OS: HR = 0.404, 95% CI = 0.230-0.709, P = 0.002). The median S1 treatment was 23 cycles. Grade 1-2 skin pigmentation, oral mucositis, and hand and foot syndrome were the main adverse reactions.

Conclusion: For metastatic NPC patients with first-line chemotherapy response, S1 MT can improve PFS and OS, with good tolerability. EBV-DNA and SAA can better help us identify patients who can benefit from MT after standard treatment.

Trial registration: The study protocol was registered at the Chinese Clinical Trial Registry (ChiCTR-IOR-16007939).

Keywords: Epstein‒Barr virus-DNA; Human serum amyloid A; Maintenance therapy; Nasopharyngeal carcinoma; Tegafur/gimeracil/oteracil.

Publication types

Randomized Controlled Trial
Multicenter Study

MeSH terms

Antineoplastic Combined Chemotherapy Protocols / therapeutic use
China
Disease Progression
Humans
Nasopharyngeal Carcinoma / drug therapy
Nasopharyngeal Neoplasms* / drug therapy
Nasopharyngeal Neoplasms* / pathology
Progression-Free Survival