and with lower toxicity, compared with a combination of radiation and concurrent chemoradiotherapy, a team of investigators in China suggest.
In a randomized phase 3 trial, there was no significant difference in 3-year failure-free survival (FFS) rates for patients with low-risk stage 2/T3N0 nasopharyngeal carcinoma (NPC) who received intensity-modulated radiation therapy (IMRT) alone, compared with patients who received a combination of IMRT and concurrent cisplatin-based chemoradiotherapy.
The trial met its primary endpoint of non-inferiority for IMRT alone with 3-year FFS rates of 90.5% for 169 patients randomized to IMRT alone, and 91.9% for the combined therapy (P for noninferiority < .001).
“The trial results were different from studies on stage 2 NPC conducted in the two-dimensional conventional radiotherapy era that showed concurrent cisplatin chemotherapy provided radio sensitization to enhance locoregional control and overall survival,” investigators Ling-Long Tang, MD and colleagues from Sun Yat-Sen University in Guanzhou, China, reported in JAMA.
“It is possible that IMRT may have maximized locoregional control in many patients with low-risk NPC, which is generally radiosensitive, as supported by more than 90% locoregional relapse-free survival rates in almost all contemporary series for stage 2 disease,” they wrote.
In addition to meeting the primary noninferiority endpoint, there were no significant differences in secondary efficacy endpoints of overall survival, locoregional relapse, or metastasis.
The safety analysis, however, showed that patients in IMRT-alone group had significantly fewer grade 3 or 4 adverse events (17% vs. 46%, 95% with a significant 95% confidence interval for the difference), and patients who received only IMRT had significantly better quality-of-life scores during radiotherapy across multiple domains.
“I expect that as a result of this study, most patients with stage 2 [Epstein-Barr virus]–associated NPC will be treated with IMRT alone,” said Lori Wirth, MD, a head and neck cancer specialist at Massachusetts General Hospital Cancer Center in Boston.
“This noninferiority study showed that IMRT alone (without concurrent cisplatin) does not lead to greater locoregional relapse or distant metastatic disease. Not only that, but also the study confirmed what we would expect that IMRT alone without concurrent cisplatin is better tolerated with less acute toxicity and improved quality of life compared to chemoRT,” she said in a comment.
“One question that remains is related to long-term toxicity: ‘Will the IMRT-alone patients also experience less lifelong toxicity from treatment?’ If yes, that would be great,” she said.
The open-label, phase 3 trial was conducted at five Chinese hospitals with a total of 341 patients randomly assigned to IMRT alone or with concurrent chemoradiotherapy consisting of IMRT with cisplatin 100 mg/m2 every 3 weeks for three cycles.
As noted before, the primary endpoint was 3-year FFS, defined as time from randomization to any disease relapse or death. The predetermined noninferiority margin was 10%.
Secondary endpoints included overall survival, locoregional relapse-free survival, distant metastasis-free survival, adverse events, and health-related quality of life measured by the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire for physical function, symptom control, or health-related quality of life.
The study was supported by grants from the National Natural Science Foundation of China, Natural Science Foundation of Guangdong Province, Key-Area Research and Development Program of Guangdong Province, Overseas Expertise Introduction Project for Discipline Innovatio, and the Sun Yat-Sen University Clinical Research 5010 Program. The authors and Dr. Wirth reported no relevant conflicts of interest.