Gemcitabine plus cisplatin provides long-term OS benefit in R/M NPC patients

First-line treatment of recurrent or metastatic (R/M) nasopharyngeal carcinoma (NPC) with gemcitabine plus cisplatin (GC) significantly improves long-term overall survival (OS) vs fluorouracil plus cisplatin (FC), according to final OS results of the phase III GEM20110714 study.

Median OS was 22.1 months in patients randomized to receive GC vs 18.6 months in the FC group (hazard ratio [HR], 0.72; 95 percent confidence interval [CI], 0.58 to 0.90; two-sided p=0.004), after a median follow-up of 69.5 months and 69.7 months, respectively. [J Clin Oncol 2021;39:3273-3282]

One-year, 3-year and 5-year OS probabilities were 79.9 percent vs 71.8 percent (p=0.093), 31.0 percent vs 20.4 percent (p=0.021), and 19.2 percent vs 7.8 percent (p<0.001), respectively, for GC vs FC.

Notably, a higher proportion of patients in the GC vs FC group survived ≥5 years (13.8 percent vs 5.5 percent). The 5-year OS rate was 19.2 percent vs 7.8 percent.

“This is the first phase III trial to demonstrate a significant OS benefit for palliative systemic chemotherapy in NPC,” the investigators noted. “GC significantly prolonged OS compared with FC, despite similar poststudy treatment. Our data support GC as standard-of-care chemotherapy in R/M NPC patients.”

In the study, 51.9 percent vs 55.2 percent of patients in the GC vs FC group received a first subsequent systemic therapy after discontinuation of study treatment, the most common being platinum-based combination chemotherapy (68.1 percent vs 83 percent). Overall response to first subsequent systemic therapy was comparable between the GC and FC groups, at a rate of 20.2 percent vs 17.0 percent.

Second or further subsequent therapy was used by 19.3 percent vs 26.0 percent of patients in the GC vs FC group, the most common agents being capecitabine (7.7 percent) and platinum (6.6 percent) in the GC group, and gemcitabine (16.6 percent) and platinum (10.5 percent) in the FC group.

The study included 362 patients with newly diagnosed stage IV NPC or recurrent NPC not suitable for local treatment, with Eastern Cooperative Oncology Group performance status (ECOG PS) of 0 or 1. The patients, enrolled from 22 sites, were randomized 1:1 to receive GC (n=181; median age, 47 years; male, 77.9 percent; type III histology, 82.9 percent) or FC (n=181; mean age, 47 years; male, 84.5 percent; type III histology, 82.9 percent) once every 21 days, for a maximum of six cycles or until disease progression, death, intolerable toxicities, or patient-physician decision.

Previously reported results of the study showed significantly improved progression-free survival (PFS) with GC vs FC (median, 7.0 months vs 5.6 months; HR, 0.55; 95 percent CI, 0.44 to 0.68; p<0.0001). [Lancet 2016;388:1883-1892] Updated PFS results (HR, 0.54; 95 percent CI, 0.43 to 0.67) were consistent with those of the primary analysis, with 1-year, 3-year and 5-year PFS probabilities of 21.2 percent vs 6.0 percent, 8.5 percent vs 1.1 percent, and 7.6 percent vs 0 percent, respectively.

“Although the study was not designed to have sufficient power to test interaction, subgroup OS analyses were generally consistent with the primary OS analysis, except in patients with de novo metastasis and those with bone metastasis,” the investigators noted. “In multivariable analysis, better survival was shown in patients randomized to receive GC [p=0.008], those with better ECOG PS [p<0.001], those without liver metastasis [p=0.05], and those with low baseline Epstein-Barr viral load [p<0.05].”