Gemcitabine Plus Cisplatin Provides Survival Benefit Over Fluorouracil Plus Cisplatin in Advanced Nasopharyngeal Carcinoma

Patients with recurrent or metastatic nasopharyngeal carcinoma who received first-line gemcitabine plus cisplatin had longer overall survival (OS) compared with fluorouracil plus cisplatin, according to the results of the phase 3 GEM20110714 study (NCT01528618) published in the Journal of Clinical Oncology.

Investigators determined that gemcitabine plus cisplatin yielded a median OS of 22.1 months (95% CI, 19.2-25.0) compared with 18.6 months (95% CI, 15.4-21.7) for fluorouracil plus cisplatin. The probability of OS was 79.9 at 1 year %, 31.0% at 3 years, and 19.2% at 5 years for gemcitabine plus cisplatin and at 71.8% at 1 year, 20.4% at 3 years, and 7.8% at 5 years for fluorouracil plus cisplatin. The OS was significantly longer in the gemcitabine plus cisplatin arm than the fluorouracil plus cisplatin (HR, 0.72; 95% CI, 0.58-0.90; 2-sided P = .004).

“The GEM20110714 study established the role of first-line [gemcitabine plus cisplatin] for patients with [recurrent or metastatic nasopharyngeal carcinoma]. Here, we report the final OS results after an additional 4 years of follow-up, which, to date, is the longest duration of follow-up in [recurrent or metastatic nasopharyngeal carcinoma]. The results show that the [gemcitabine plus cisplatin] regimen produces an OS benefit for these patients, with a 28% reduction in the risk of death and an improvement of almost 4 months in median OS,” the study’s investigators wrote.

A total of 362 patients were enrolled on the trial and were randomized 1:1 to receive either gemcitabine plus cisplatin (n = 181) or the fluorouracil plus cisplatin (n = 181). Patients in the experimental cohort received 1 g/m2 of intravenous gemcitabine once daily on days 1 and 8, as well as 80 mg/m2 of cisplatin once daily on day 1. In the control arm, patients were treated with 4 g/m2 of continuous intravenous fluorouracil starting from day 1 and 80 mg/m2 of cisplatin on day 1.

In December of 2020, the duration of follow-up was comparable between the 2 cohorts, including 69.5 months (95% CI, 63.3-75.6) with gemcitabine plus cisplatin and 69.7 months (95% CI, 56.4-83.0) for fluorouracil plus cisplatin. Of this population, 86.7% died (n = 314), including 81.8% (n = 148) of the gemcitabine plus cisplatin arm and 91.7% (n = 166) of the fluorouracil plus cisplatin arm. The restricted mean value time for OS was 33.0 months (95% CI, 29.3-37.2) in the gemcitabine plus cisplatin group and 25.4 months (95% CI, 22.4-28.6) in the fluorouracil plus cisplatin group (P = .003).

After discontinuing treatment, 51.9% (n = 94) of patients in the gemcitabine plus cisplatin group and 55.2% (n = 100) of patients in the fluorouracil plus cisplatin group started a first subsequent systemic therapy. Within this population, 68.1% (n = 64) and 83.0% (n = 83) received a platinum-based combination therapy in both the gemcitabine plus cisplatin and fluorouracil plus cisplatin groups, respectively.

The overall response rate for patients who received a first subsequent treatment in the gemcitabine plus cisplatin arm was 20.2%. Additionally, 44.7% of patients experienced stable disease and 23.4% developed progressive disease. Patients in the fluorouracil plus cisplatin arm who received a first subsequent therapy had a partial response of 17.0%, 52.0% had stable disease, and 20% developed progressive disease. The data for OS were censored at initiation of second-line therapy, with significantly longer OS in the gemcitabine plus cisplatin arm at 29.3 months compared with the fluorouracil plus cisplatin arm at 16.1 months (HR, 0.51; 95% CI, 0.36-0.71; P < .001).

Additionally, a second subsequent therapy was administered to 37.2% (n = 35) of patients in the gemcitabine plus cisplatin arm and 47.0% (n = 47) of patients in the fluorouracil plus cisplatin arm. A total of 42 patients who were assigned to the gemcitabine poststudy treatment arm received fluorouracil, capecitabine, tegafur, or S-1. Moreover, 47 patients in the fluorouracil plus cisplatin arm \ received gemcitabine after discontinuation of study treatment. Ten patients from each arm received immune checkpoint inhibitors. In this group, 30.0% achieved a partial response, 30.0% had stable disease, and 40.0% developed progressive disease.

There were 25 patients in the gemcitabine plus cisplatin arm who survived 5 years or more. By year 5, 4 patients had not progressed, 15 patients had progressed, and 6 patients had been censored for progression-free survival (PFS). In the fluorouracil plus cisplatin arm, there were 10 survivors of 5 years or more, of which 9 had progressed, and 1 was censored for PFS at 11.5 months.

The PFS rates consistently favored gemcitabine plus cisplatin compared with fluorouracil plus cisplatin with a similar risk of disease progression or death. The PFS probabilities in the gemcitabine plus cisplatin and fluorouracil plus cisplatin arms was 21.2% (15.5%-27.6%) vs 6.0% (95% CI, 3.1%-10.3%) at 1 year, 8.5% (95% CI, 4.6%-13.9%) vs 1.1% (95% CI, 0.1%-4.8%) at 3 years, and 7.6% (95% CI, 3.9%-12.9%) vs 0% at 5 years (all with P values of < .001).

Reference:

Hong S, Zhang Y, Yu G, et al. Gemcitabine plus cisplatin versus fluorouracil plus cisplatin as first-line therapy for recurrent or metastatic nasopharyngeal carcinoma: final overall survival analysis of GEM20110714 phase III study. J Clin Oncol. Published Online August 11, 2021. doi:10.1200/JCO.21.00396