In patients with N2 and N3 nasopharyngeal carcinoma, adjuvant treatment with concurrent gemcitabine and cisplatin significantly improved progression-free survival, with acceptable toxicity, over fluorouracil plus cisplatin, according to a phase III trial reported from Sun Yat-sen University Cancer Center, Guangzhou, China.1
Lin-Quan Tang, MD, PhD, who presented the findings at the 2023 ASCO Annual Meeting, noted that the current practice of treating with adjuvant fluorouracil plus cisplatin may not be adequate for tumor control in high-risk patients. To potentially identify a more effective regimen, the researchers evaluated concurrent radiotherapy plus cisplatin (100 mg/m2) on days 1, 22, and 43 followed by three cycles with one of two adjuvant regimens:
Cisplatin plus gemcitabine has been shown superior to fluorouracil plus cisplatin in the metastatic setting, so the study was asking whether moving it to the adjuvant setting would also be beneficial.
Key Study Results
For the 240 patients enrolled in this open-label study, the objective response to chemoradiotherapy was high and comparable in both arms: 97.4% with fluorouracil plus cisplatin and 96.7% with gemcitabine plus cisplatin. Complete responses were observed in 92.5% and 95.0%, respectively. In addition, at the completion of chemoradiotherapy, Epstein-Barr virus (EBV) clearance was high in both groups, with no EBV DNA detected in 92.7% and 94.8% of patients, respectively.
The substitution of gemcitabine for fluorouracil resulted in a significant increase in 3-year progression-free survival, the study’s primary endpoint. At 3 years, 83.9% of those given gemcitabine plus cisplatin were free of disease progression, compared with 71.5% of those given fluorouracil plus cisplatin (hazard ratio [HR] = 0.54; P = .023), Dr. Tang reported. Benefits were also seen for distant metastasis–free survival (HR = 0.50; P = .042) and locoregional relapse (HR = 0.33; P = .03), but overall survival remains similar at this time. The performance of the control arm was consistent withthat seen in a recent meta-analysis.2
Grade ≥ 3 hematologic toxicities were increased with gemcitabine plus cisplatin vs fluorouracil plus cisplatin, including leukopenia (52% vs 29%), neutropenia (32% vs 16%), and thrombocytopenia (9% vs 5%), but diarrhea was not (0% vs 5%).
“We highly recommend adjuvant gemcitabine plus cisplatin for patients with locally advanced nasopharyngeal cancer, but longer follow-up is required to confirm whether this regimen is beneficial for overall survival,” Dr. Tang said.
Barbara Burtness, MD, the Anthony N. Brady Professor of Medicine and Chief Translational Research Officer at Yale Cancer Center, New Haven, Connecticut, included this study in her ASCO Highlights of the Day presentation at the annual meeting. She noted: “Despite the somewhat lower use of adjuvant chemotherapy with gemcitabine plus cisplatin (completed by 62% vs 77% of the standard arm), there was a significant benefit for the substitution of gemcitabine after chemoradiation. The progression-free survival was comparable to that seen in the gemcitabine plus cisplatin induction studies in the preimmunotherapy era.”
Barbara Burtness, MD
Dr. Burtness continued: “However, toxicity was increased relative to fluorouracil plus cisplatin, and the overall survival data are not mature, so I don’t think this impacts our choice of therapy at the moment.” She further noted that with gemcitabine plus cisplatin generally being the preferred induction chemotherapy already, the study’s findings regarding postradiation adjuvant chemotherapy for those not given induction chemotherapy will probably impact only a small proportion of patients.
DISCLOSURE: Dr. Tang reported no conflicts of interest. Dr. Burtness has served as a consultant or advisor to AbbVie, ALX Oncology, Arvinas, Coherus Biosciences, CUE Biopharma, Genentech/Roche, IO Biotech, Kura Oncology, MacroGenics, Merck, Merck KGaA, and Vaccinex.
1. Tang LQ, Liu LT, Liu H, et al: Concurrent chemoradiotherapy followed by adjuvant cisplatin-gemcitabine versus cisplatin-5-fluorouracil chemotherapy for N2-3 nasopharyngeal carcinoma: A multicentre, open-label, randomised, controlled phase 3 trial. 2023 ASCO Annual Meeting. Abstract 6000. Presented June 5, 2023.
2. Blanchard P, Lee AWM, Carmel A, et al: Meta-analysis of chemotherapy in nasopharynx carcinoma (MAC-NPC): An update on 26 trials and 7,080 patients. Clin Transl Radiat Oncol 32:59-68, 2021.