Adjuvant capecitabine in locoregionally advanced nasopharyngeal carcinoma: A multicenter randomized controlled phase III trial.

Authors

Jingjing Miao

Jingjing Miao

Department of Nasopharyngeal Carcinoma, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Guangzhou, China

Jingjing Miao , Lin Wang , Sze Huey Tan , Jin-Gao Li , Junlin Yi , Ye Zhang , Xiaochang Gong , Xiang Yanqun , Qiu-Yan Chen , Mingyuan Chen , Xing Lv , Weixiong Xia , Lin-Quan Tang , Xiao-Wu Deng , Xiang Guo , Hai-Qiang Mai , Fei Han , Melvin Lee Kiang Chua , Chong Zhao

Organizations

Department of Nasopharyngeal Carcinoma, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Guangzhou, China, Division of Clinical Trials & Epidemiological Sciences, National Cancer Centre Singapore, Singapore, Singapore, Jiangxi Provincial Tumor Hospital, Nanchang, China, Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China, National Cancer Center, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China, Department of Radiation Oncology, Jiangxi Province Tumor Hospital, Nanchang, China, Sun Yat-sen University Cancer Center, Guangzhou, China, Department of Nasopharyngeal Carcinoma, Sun Yat-sen University Cancer Center, Guangzhou, China, Department of Radiation Oncology, Sun Yat-sen University Cancer Centre, State Key Laboratory of Oncology in South China, Collaborative Innovation Centre for Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Guangzhou, China, Sun Yat-sen Univerisity Cancer Center, Guangzhou, China, National Cancer Centre Singapore, Singapore, Singapore, Cancer Center, Sun Yat-sen University, Guangzhou, China

Research Funding

Other Foundation
National Natural Science Foundation of China [No. 81872469 and 82073330]; Wu Jieping Medical Foundation [No. 320.6750.19089 and 320.6750.17108]; Sun Yat-sen University Cancer Center 308 Program

Background: We conducted a multicenter, randomized controlled phase III clinical trial (NCT02143388) to investigate the efficacy and toxicity of adjuvant capecitabine (AC) in addition to concurrent cisplatin and radiotherapy (CCRT) compared to CCRT alone in high-risk locoregionally advanced nasopharyngeal carcinoma (LANPC) patients. Methods: Eligibility criteria included AJCC/UICC 7th ed TNM stage III-IVb and one of the following features: T3-4N2 or T1-4N3 or pre-treatment plasma EBV DNA concentration of >20,000 copy/ml or gross primary tumor volume (GTVnx) of >30 cm3 or a maximum standard uptake value (SUVmax) of >10.0 by 18FDG PET-CT within the primary tumor or multiple neck node metastases, with any larger than 4 cm. All patients were randomly assigned in a 1:1 ratio to receive CCRT (3-weekly cisplatin at 100 mg/m2 for 2-3 cycles) followed by AC (1000 mg/m2 bi-daily for 14 days every 21-day cycle for 8 cycles), or CCRT alone. The prescribed radiation doses were 68-72 Gy/30-32 fractions to the PTVnx, 60-68 Gy/30-32 fractions to PTVnd, 60-64Gy/30-32 fractions to PTVhigh-risk, 54-58Gy/30-32 fractions to PTVlow-risk. Primary end point was failure-free survival (FFS). Results: Between Mar 2014 to Jul 2018, 180 patients were recruited (90 patients in CCRT+AC arm and 90 in CCRT alone arm). All patients completed RT and ≥2 cycles of concurrent cisplatin in both treatment arms (cumulative dose intensities for cisplatin were 200 mg/m2 in both arms). 85 (94.4%) patients went on to receive AC, with 71 (78.9%) patients completing 8 cycles; 19 (22.4%) patients had dose reduction of AC. With a median follow-up of 44.8 mo, the 3-y FFS was significantly superior in the CCRT+AC arm than the CCRT arm for the intention-to-treat cohort (87.7% vs 73.3%; HR: 0.52 [95% CI: 0.29-0.77], P = 0.037). 3-year overall, distant metastasis-free and locoregional relapse-free survival were 92.6% vs 88.9% (HR [95% CI]: 0.66 [0.28-1.59]), 88.8% vs. 81.1% (HR: 0.67 [0.33-1.33]) and 91.5% vs 80.0% (HR: 0.50 [0.25-1.00]), respectively. Incidences of G3-4 acute toxicities were 57.8% (52 of 90) in CCRT+AC arm and 51.1% (46 of 90) in CCRT alone arm, with a higher incidence of hand foot syndrome (3.5% vs 0%), xerostomia (11.1% vs 3.3%), mucositis (23.3% vs 16.7%), and anemia (5.6% vs 2.2%) in the CCRT+AC arm. G3-4 late toxicities occurred in 13.3% (12 of 90) and 9.0% (8 of 89), respectively. Conclusions: The addition of capecitabine to CCRT conferred a superior disease control than CCRT alone in high-risk LANPC. Survivals in ITT and PP set. Clinical trial information: NCT02143388

Variable
ITT
PP
CCRT+AC

(N = 90)
CCRT alone

(N = 90)
CCRT+AC

(N = 71)
CCRT alone

(N = 90)
FFSFailure or death, N (%)15 (16.7)27 (30.0)8 (11.3)27 (30.0)
3-y FFS, %87.773.392.973.3
OSDeath, N (%)8 (8.9)12 (13.3)3 (4.2)12 (13.3)
3-y OS, %92.688.998.688.9
DMFSDistant metastasis or death, N (%)13 (14.4)19 (21.1)6 (8.5)19 (21.1)
3-y DMFS, %88.881.194.381.1

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Abstract Details

Meeting

2021 ASCO Annual Meeting

Session Type

Oral Abstract Session

Session Title

Head and Neck Cancer

Track

Head and Neck Cancer

Sub Track

Local-Regional Disease

Clinical Trial Registration Number

NCT02143388

Citation

J Clin Oncol 39, 2021 (suppl 15; abstr 6005)

DOI

10.1200/JCO.2021.39.15_suppl.6005

Abstract #

6005

Abstract Disclosures