Adjuvant Capecitabine Plus Concurrent CRT Yields FFS Benefit in Locoregionally Advanced LA-NPC

The addition of adjuvant capecitabine (Xeloda) to concurrent chemoradiotherapy (CRT) was well-tolerated and improved failure-free survival (FFS) compared with CRT alone among patients with locoregionally advanced nasopharyngeal carcinoma, according to data from a randomized clinical trial (NCT02143388) published in JAMA Oncology.

At a median follow-up of 58 months, the 3-year and 5-year FFS rates in the adjuvant capecitabine and control groups, respectively, were 83.3% (95% CI, 73.9%-89.6%) vs 72.2% (95% CI, 61.7%-80.3%) and 78.5% (95% CI, 67.7%-86.0%) vs 65.9% (95% CI, 54.3%-75.2%; HR, 0.53; 95% CI, 0.30-0.94; P = .03). Additionally, the 3-year and 5-year overall survival (OS) rates for each respective cohort was 93.3% (95% CI, 85.8%-96.9%) vs 87.8% (95% CI, 79.0%-93.0%) at 3 years and 87.8% (95% CI, 78.0%-93.3%) vs 82.1% (95% CI, 71.7%-89.0%).

Investigators enrolled a total of 180 patients with locoregionally advanced nasopharyngeal carcinoma on the multicenter, open-label randomized trial. All patients received concurrent CRT and 100 mg/m2 of intravenous cisplatin (Platinol) every 3 weeks for 2 to 3 cycles depending on the duration of radiotherapy. Patients were randomly assigned to receive the addition of 1000 mg/m2 of oral capecitabine twice daily for 14 days every 21.

The primary end point of the trial was FFS. Secondary end points included OS, distant metastasis-free survival, and locoregional relapse-free survival.

Patients who were 18 to 70 years of age with histologically confirmed, newly diagnosed, nonkeratinizing nasopharyngeal carcinoma were eligible to enroll on the study. Additional eligibility criteria included having a Karnofsky performance status of at least 80 points; TNM stage III to IVb disease; no prior radiotherapy, chemotherapy, or surgery; and adequate organ function. Additionally, eligible patients needed to have at least 1 unfavorable high-risk factor including T3-4N2 or T1-4N3; plasma Epstein-Barr virus (EBV) DNA titer higher than 20,000 copies/mL; primary gross tumor volume (GTV) larger than 30.0 cm3; a maximum standard uptake value of primary GTV higher than 10.0 on 18F-FDG PET/CT topography; or multiple nodal metastases larger than 4.0 cm in size.

The median patient age was 47 years (interquartile range, 40-55), and 79.4% of patients were men. Investigators reported that pretreatment patient characteristics were comparable between treatment groups. A total of 84.4% (n = 79/90) of patients in the capecitabine cohort and 88.9% (n = 80/90) of those in the control group had at least 2 high-risk factors. All patients completed concurrent CRT except for 1 patient in the capecitabine group who received 1 cycle of cisplatin. In the experimental group, 94.4% of patients received capecitabine, of whom 78.9% completed 8 treatment cycles.

Trial investigators reported no interaction between high-risk factors and the study treatment. However, the addition of adjuvant capecitabine favored the subgroup of patients who had risk factors with a maximum standard uptake value higher than 10.0, a primary GTV larger than 30.0 cm3, and EBV DNA higher than 20,000 copies/mL. An exploratory analysis indicated that patients with detectable EBV DNA titer following concurrent CRT had lower FFS rates compared with those who did not have detectable EBV DNA titer, but statistical significance was not reached for these data.

The incidence of grade 3 treatment-related adverse effects (TRAEs) in the capecitabine and control groups, respectively, were 60.0% vs 51.1%. The most frequently observed TRAEs in each respective group included xerostomia (18.9% vs 10.0%), mucositis (23.3% vs 16.7%), and anorexia (8.9% vs 4.4%). The incidence of grade 3/4 delayed TRAEs in each group was 10.8% vs 8.6%, respectively.

Reference

Miao J, Wang L, Tan SH, et al. Adjuvant capecitabine following concurrent chemoradiotherapy in locoregionally advanced nasopharyngeal carcinoma: a randomized clinical trial. JAMA Oncol. Published online October 13, 2022. doi:10.1001/jamaoncol.2022.4656