JAMA Oncol
Efficacy and Safety of Locoregional Radiotherapy With Chemotherapy vs Chemotherapy Alone in De Novo Metastatic Nasopharyngeal Carcinoma: A Multicenter Phase 3 Randomized Clinical Trial.
ABSTRACT
Importance
The 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.
Interventions
The chemotherapy regimens were fluorouracil continuous intravenous infusion at 5 g/m2 over 120 hours and 100 mg/m2 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 Measures
The primary end point of the study was overall survival (OS). The secondary end point was progression-free survival (PFS) and safety.
Results
Overall, 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 Relevance
In this randomized clinical trial, radiotherapy added to chemotherapy significantly improved OS in chemotherapy-sensitive patients with mNPC.
Trial Registration
ClinicalTrials.gov Identifier: NCT02111460.
Related Questions
Would you add radiation, if so any concurrent systemic therapy?
Would you consider hypofractionation, if so, what dose/fx and reference for constrain...
New comment by Radiation Oncologist at Baylor College of Medicine ( April 27, 2021)
There is a phase II trial from Hong Kong as well showing survival advantage with consolidative radiation.
https://clinicaltrials.gov/ct2/show/NCT02476669
Would you consider ...
What are the data for loco-regional and distant recurrence rates with and without local therapy? What is the OS advantage?
New answer by Radiation Oncologist at Medical University of South Carolina (Charleston) (September 30, 2021)
Yes. Please refer to the recent small phase III randomized trial: You et al., PMID 32701129. Anecdotally, I have treated an Asian patient with EBV-associated NPC who had ...
How do you decide if/when to treat the primary disease and when would you treat definitively?
New comment by Radiation Oncologist at Stroger Hospital ( December 18, 2022)
Great discussion.