Chemoradiotherapy is the standard of care for patients with nasopharyngeal carcinoma. Despite this treatment, however, the disease will ultimately be fatal in approximately 70% of patients. Now, data from a large-cohort, open-label phase III randomized controlled trial demonstrate that the addition of induction chemotherapy to chemoradiotherapy leads to improved survival outcomes.

A total of 480 patients with locoregionally advanced nasopharyngeal carcinoma were randomized (1:1) to receive chemoradiotherapy with, or without, 3 prior cycles of gemcitabine plus cisplatin induction chemotherapy. Recurrence-free survival (RFS) was the primary end point.

Virtually all patients (94.6%) responded to induction chemotherapy. After a median follow-up duration of 42.7 months, patients in the induction chemotherapy group had significantly improved 3-year RFS (85.3% versus 76.5%, hazard ratio (HR) for disease recurrence or death 0.51, 95% CI 0.34–0.77; P = 0.001). Patients receiving induction chemotherapy also had improved 3-year overall survival (94.6% versus 90.3%, respectively, HR 0.43, 95% CI 0.24–0.77). Interestingly, however, no significant differences in 3-year locoregional RFS emerged from the analysis (91.8% versus 91.0%, HR for locoregional recurrence or death 0.77, 95% CI 0.42–1.41).

Patients receiving induction chemotherapy had an increased risk of adverse events: acute grade 3–4 adverse events occurred in 75.7% of patients versus 55.7% of those receiving chemoradiotherapy only, although the risk of late-onset serious adverse events was similar (9.2% versus 11.4%).

These data demonstrate that induction chemotherapy improves the efficacy of chemoradiotherapy, albeit with a substantial increase in the risk of adverse events. Longer follow-up monitoring will be required to determine the balance between tolerability and the risk of mortality associated with receiving chemoradiotherapy only.