Efficacy and Safety of Locoregional Radiotherapy With Chemotherapy vs Chemotherapy Alone in De Novo Metastatic Nasopharyngeal Carcinoma

Abstract

IMPORTANCEThe role of locoregional radiotherapy in patients with de novo metastatic nasopharyngeal carcinoma (mNPC) is unclear.OBJECTIVE To investigate the efficacy and safety of locoregional radiotherapy in de novo mNPC.DESIGN, SETTING, AND PARTICIPANTS Patients with biopsy-proven mNPC, who demonstrated complete or partial response (RECIST v1.1) following 3 cycles of cisplatin and fluorouracil chemotherapy, were enrolled. Eligible patients were randomly assigned (1:1) to receive either chemotherapy plus radiotherapy or chemotherapy alone. Overall, 126 of 173 patients screened were eligible to the study, and randomized to chemotherapy plus radiotherapy (n = 63) or chemotherapy alone (n = 63). Median (IQR) follow-up duration was 26.7 (17.2-33.5) months. INTERVENTIONSThe chemotherapy regimens were fluorouracil continuous intravenous infusion at 5 g/m 2 over 120 hours and 100 mg/m 2 intravenous cisplatin on day 1, administered every 3 weeks for 6 cycles. Patients assigned to the chemotherapy plus radiotherapy group received intensity-modulated radiotherapy (IMRT) after chemotherapy. MAIN OUTCOMES AND MEASURESThe primary end point of the study was overall survival (OS). The secondary end point was progression-free survival (PFS) and safety. RESULTSOverall, 126 patients were enrolled (105 men [83.3%] and 21 women [16.7%]; median [IQR] age, 46 [39-52] years). The 24-month OS was 76.4% (95% CI, 64.4%-88.4%) in the chemotherapy plus radiotherapy group, compared with 54.5% (95% CI, 41.0%-68.0%) in the chemotherapy-alone group. The study met its primary end point of improved OS (stratified hazard ratio [HR], 0.42; 95% CI, 0.23-0.77; P = .004) in favor of chemotherapy plus radiotherapy. Progression-free survival was also improved in the chemotherapy plus radiotherapy group compared with the chemotherapy-alone group (stratified HR, 0.36; 95% CI, 0.23-0.57). No significant differences in acute hematological or gastrointestinal toxic effects were observed between the treatment arms. The frequency of acute grade 3 or higher dermatitis, mucositis, and xerostomia was 8.1%, 33.9%, and 6.5%, respectively, in the chemotherapy plus radiotherapy group. The frequency of late severe grade 3 or higher hearing loss and trismus was 5.2% and 3.4%, respectively, in the chemotherapy plus radiotherapy group. CONCLUSIONS AND RELEVANCEIn this randomized clinical trial, radiotherapy added to chemotherapy significantly improved OS in chemotherapy-sensitive patients with mNPC.

<p>Synchronous Metastatic Nasopharyngeal Carcinoma: Characteristics and Survival of Patients Adding Definitive Nasopharyngeal-Neck Radiotherapy to Systematic Chemotherapy</p>

“… 24 A multicenter randomized clinical trial including 126 smNPC showed that the 2-year OS of patients receiving nasopharyngeal-neck RT plus systematic CT was 76.4%, while the 2-year OS of patients receiving systematic CT was only 54.5% (HR = 0.42, 95% CI = 0.42, p = 0.004). 25 In our study, we also confirmed that the addition of nasopharyngeal-neck RT considerably increased the median OS of smNPC patients by 18.8 months compared to those with systematic CT, and reduced the risk of mortality by 51% in our multivariate analysis.…”

Prognostic model for risk stratification of de novo metastatic nasopharyngeal carcinoma patients treated with chemotherapy followed by locoregional radiotherapy

“… 5 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 A recent phase III randomized clinical trial reported the efficacy of definitive LRRT in addition to palliative chemotherapy in patients with de novo mNPC. 8 The study demonstrated that high-dose LRRT to the primary and nodal regions resulted in a significant survival benefit in a highly selected subgroup of patients with de novo mNPC, who had shown satisfactory response to first-line chemotherapy. The results indicate chemotherapy followed by high-dose LRRT could be a promising treatment strategy and should be considered for chemotherapy-sensitive patients with de novo mNPC.…”

“…Recently, a randomized phase III clinical trial, for the first time, demonstrated that LRRT added to chemotherapy significantly improved overall survival (OS) in patients with de novo mNPC who showed a satisfactory response to chemotherapy. 8 The study suggested that incorporating LRRT with chemotherapy could be an effective treatment modality for de novo mNPC. However, the results also indicated that the role of LRRT among the nonresponders to chemotherapy remains unclear.…”

A Scoring System Based on Nutritional and Inflammatory Parameters to Predict the Efficacy of First-Line Chemotherapy and Survival Outcomes for De Novo Metastatic Nasopharyngeal Carcinoma

“…[29][30][31] In addition to systemic therapy, locoregional radiotherapy combined with chemotherapy was associated with significantly prolonged OS in chemotherapy-sensitive de novo mNPC patients. 21,22 Therefore, we believe that the pretherapy prediction of first-line chemotherapy efficacy is crucial for the timely identification of patients who might have an inadequate response to chemotherapy, allowing personalized treatment recommendations to be designed from the start.…”

“…20 Our previous work and an updated clinical trial have confirmed that additional locoregional radiotherapy can significantly improve survival among those who show satisfactory first-line chemotherapy responses. 21 , 22 However, roughly 35% of all de novo mNPC patients do not exhibit satisfactory responses to first-line chemotherapy. These patients represent an under-appreciated subgroup that might require more intense therapy.…”