Triplet Induction Regimen Bests Doublet for Nasopharyngeal Carcinoma

Induction chemotherapy with paclitaxel, cisplatin, and capecitabine (TPC) significantly improved failure-free survival (FFS) compared with cisplatin and fluorouracil (PF) in patients with advanced nasopharyngeal carcinoma (NPC), a phase III randomized trial from China showed.

Among 238 eligible patients in the intention-to-treat population who subsequently underwent chemoradiotherapy, the 3-year FFS rate was 83.5% in those who received the TPC regimen compared with 68.9% in those who received PF (stratified HR 0.47, 95% CI 0.28-0.79, P=0.004), reported Wei-Xiong Xia, MD, of Sun Yat-sen University Cancer Center in Guangzhou, and colleagues.

Over the median follow-up of 48.4 months, patients who received induction with TPC also had a significant reduction in the risk of distant metastases (91.4% vs 80.4% in the PF arm; stratified HR 0.49, 95% CI 0.24-0.98, P=0.04) and locoregional recurrence (93.8% vs 87.4%, respectively; stratified HR 0.40, 95% CI 0.18-0.93, P=0.03), they wrote in JAMA Oncology.

However, there was no significant difference in early overall survival (OS; stratified HR 0.45, 95% CI 0.17-1.18, P=0.10). “A longer follow-up is needed to confirm whether there is a benefit of OS,” Xia and team noted.

“Both adjuvant chemotherapy and induction chemotherapy improve patient outcomes in advanced NPC when sequenced with concurrent chemoradiotherapy, but the dilemma one faces is in validating the superiority of one sequence over the other,” wrote Maurice Willis, MD, of the University of Texas Medical Branch in Galveston and the University of Texas MD Anderson Cancer Center in Houston, in an invited commentary.

“Although one needs to exercise caution extrapolating these results clinically until more enduring mature results are available, this trial addresses an unmet need and brings TPC into the armamentarium for induction therapies in advanced NPC,” he added.

In this multicenter trial, 238 eligible patients (78.6% men, median age 45 years) with stage IVA to IVB NPC were randomly assigned 1:1 to induction chemotherapy with two 21-day cycles of TPC or PF followed by chemoradiotherapy. The primary endpoint of FFS was defined as the interval between randomization and the first documented tumor recurrence, death, or the last follow-up, whichever occurred first.

At 12 weeks after chemoradiotherapy, more patients in the TPC group showed a complete response (94.1% vs 85.0% in the PF group; P=0.04).

Overall, 63 patients had disease recurrence or died (22 in the TPC group and 41 in the PF group).

“The major downfall of most induction therapies is toxicity,” Willis noted in his commentary. However, more than 90% of patients in this study were able to maintain dose intensity during induction therapy and complete their chemoradiotherapy, he pointed out.

Dose reductions or discontinuations of induction chemotherapy were more common in the PF group than in the TPC group (13.3% vs 5.9%).

Grade 3 to 4 acute adverse events were reported in 68 patients in the TPC group compared with 79 patients in the PF group. One treatment-related death occurred in the PF group.