Triplet Induction Chemotherapy Improves FFS in Nasopharyngeal Carcinoma Vs Doublet Regimen

An induction chemotherapy regimen consisting of a combination of paclitaxel, cisplatin, and capecitabine appeared to safely improve failure-free survival (FFS) after 2 cycles compared with cisplatin and fluorouracil in patients with advanced nasopharyngeal carcinoma, according to findings from a phase 3 study (NCT02940925) published in JAMA Oncology.

At a median follow-up of 48.4 months (IQR, 39.6-53.3), patients assigned to the paclitaxel, cisplatin, and capecitabine group demonstrated a 3-year FFS rate of 83.5% (95% CI, 77.0%-90.6%) compared with 68.9% (95% CI, 61.1%-77.8%) in the cisplatin and fluorouracil group (Hazard ratio [HR], 0.47; 95% CI, 0.28-0.79; P = .004).

“Taxanes have shown promise in induction chemotherapy for advanced head and neck cancer, including nasopharyngeal cancer,” the authors of the study wrote. “A triplet induction regimen with cisplatin, fluorouracil, and a taxane might be more efficacious than cisplatin and fluorouracil. Furthermore, replacing continuous fluorouracil infusion with oral capecitabine during induction chemotherapy has the advantages of convenience, good compliance, and favorable efficacy and safety.”

The phase 3 study included 238 patients with nasopharyngeal carcinoma who were treated at 4 Chinese hospitals between October 20, 2016 and August 29, 2019. Patients’ ages ranged from 18 to 65 years old, with a median age of 45 years. All patients had untreated, nonkeratinizing stage IVA to IVB disease with an ECOG performance status of 0 or 1. Patients were randomly assigned to undergo 1 of 2 regimens: either two 21-day cycles of intravenous paclitaxel at a dose of 150 mg/m², intravenous cisplatin at 60 mg/m² on day 1, and oral capecitabine at a dose of 1000 mg/m² twice a day on days 1 to 14; or intravenous cisplatin at a dose of 100 mg/m² on day 1 and fluorouracil at a dose of 800 mg/m² daily on days 1 to 5. Both regimens were followed by 2 cycles of concurrent chemoradiotherapy.

Patients assigned to the triplet cohort experienced a lower incidence of distant metastases (stratified HR, 0.49; 95% CI, 0.24-0.98; P = .04), as well as a reduction in risk for locoregional recurrence (stratified HR, 0.40; 95% CI, 0.18-0.93; P = .03) compared with the doublet cohort. The 3-year locoregional recurrence rate in each respective arm was 93.8% (95% CI, 89.5%-98.4%) and 87.4% (95% CI, 81.4%-93.8%) The 3-year overall survival (OS) was 94.7% (95% CI, 90.6%-98.9%) in the triplet arm compared with 88.9% (95% CI, 83.4%-94.8%) in the doublet arm (stratified HR, 0.45; 95% CI, 0.17-1.18; P = .10).

The two groups showed similar rates of grade 3 and 4 adverse effects (AEs), occurring in 57.6% (n = 68) of those assigned to the triplet therapy compared with 65.8% (n = 79) in the doublet group. Common high-grade AEs in each respective group included mucositis (28.0% vs 28.3%), nausea (15.3% vs 20.8%), vomiting (18.6% vs 15.8%), and neutropenia (12.7% vs 18.3%). Grade 4 AEs occurred in 13.6% (n = 16) and 17.9% (n = 21) of patients, respectively. One patient in the cisplatin/fluorouracil group died due to treatment-related AEs.

Investigators acknowledged that the study’s limitations included its focused on patients from China, where more than 95% of all nasopharyngeal carcinoma cases are nonkeratinizing; it excluded children, adolescents and the elderly patients; and did not demonstrate a significant effect on OS. Longer follow-up would be necessary to determine possible impacts upon OS. Furthermore, the investigators did not determine the optimal number of cycles of induction therapy for this group of patients.

“To our knowledge, this phase 3 randomized clinical trial of patients with stage IVA to IVB nasopharyngeal carcinoma is the first study to show the advantage of induction chemotherapy with paclitaxel, cisplatin, and capecitabine followed by chemoradiotherapy compared with induction chemotherapy with cisplatin and fluorouracil followed by chemoradiotherapy. Our study showed that induction chemotherapy with paclitaxel, cisplatin, and capecitabine improved FFS with no increase in toxicity. The paclitaxel, cisplatin, and capecitabine group had a lower incidence of distant metastases and locoregional relapse than the cisplatin and fluorouracil group, but the effect of [the triplet regimen] on early OS was not significant,” the investigators concluded.

Reference

Li WZ, Lv X, Hu D, et al. Effect of induction chemotherapy with paclitaxel, cisplatin, and capecitabine vs cisplatin and fluorouracil on failure-free survival for patients with stage IVA to IVB nasopharyngeal carcinoma. JAMA Oncol. 2022;8(5):706-714. doi:10.1001/jamaoncol.2022.0122