Induction Chemotherapy Followed by Radiotherapy vs Chemoradiotherapy in Nasopharyngeal Carcinoma

Abstract

ImportanceInduction chemotherapy plus concurrent chemoradiotherapy is recommended for locoregionally advanced nasopharyngeal carcinoma but is associated with higher rates of acute toxic effects and low compliance. Evidence on de-escalating treatment intensity after induction chemotherapy is limited.ObjectiveTo assess if radiotherapy was noninferior to chemoradiotherapy after induction chemotherapy for locoregionally advanced nasopharyngeal carcinoma.Design, Setting, and ParticipantsFrom April 2015 to March 2018, a multicenter, open-label, randomized, noninferiority, phase 3 trial was conducted at 5 Chinese hospitals. A total of 383 patients aged 18 to 70 years with an untreated histologically confirmed nonkeratinizing tumor, Karnofsky performance status score not worse than 70, proper organ function, and stage III to IVB nasopharyngeal cancer were enrolled. Data were analyzed from April 2023 to June 2023.InterventionsPatients were assigned randomly. Both groups received 3 cycles of induction chemotherapy consisting of intravenous administration (on day 1) of cisplatin at 60 mg/m2 and docetaxel at 60 mg/m2 and continuous intravenous infusion (from day 1 to day 5) of daily fluorouracil (600 mg/m2), repeated every 21 days. Subsequently, the patients received radiotherapy alone (induction chemotherapy in combination with radiotherapy [IC-RT] group) or concomitant cisplatin (30 mg/m2/week) with radiotherapy for 6 to 7 weeks (induction chemotherapy combined with chemoradiotherapy [IC-CCRT] group).Main Outcomes and MeasuresThe primary end point was 3-year progression-free survival (time from the initiation of therapy until the first indication of disease progression or death), with a noninferiority margin of 10%. The secondary end points included overall survival, locoregional failure-free survival, distant metastasis-free survival, response rate, and toxic effects.ResultsA total of 383 patients (median [range] age, 48 [19-70] years; 100 women [26%]). Median follow-up time was 76 months (IQR, 70-89 months). The 3-year progression-free survival was 76.2% and 76.8% in the IC-RT (n = 193) and IC-CCRT groups (n = 190), respectively, in the intention-to-treat population, showing a difference of 0.6% (95% CI, –7.9% to 9.1%; P = .01 for noninferiority). Identical outcomes were reported in the per-protocol population. The incidence of grade 3 to 4 short-term toxic effects in the IC-RT group was less than the IC-CCRT group. No differences were observed in late toxic effects.Conclusions and RelevanceThe results of this randomized clinical trial suggest that after induction chemotherapy for locoregionally advanced nasopharyngeal carcinoma, radiotherapy alone was noninferior to chemoradiotherapy in terms of 3-year progression-free survival.Trial RegistrationClinicalTrials.gov Identifier: NCT02434614

Chemotherapy, Radiation Therapy, and Nasopharyngeal Carcinoma

“…Second, this study did not provide subgroup analysis for different stages. Such information would be crucial to identify the specific patients suitable for the disintensified treatments in clinical practice because this study enrolled patients with heterogeneous stages encompassing III to IVB.…”

“…To the Editor A recent randomized clinical trial reported that after induction chemotherapy (IC), patients with stages III to IVB ( American Joint Committee on Cancer Staging Manual, 7th Edition ) nasopharyngeal carcinoma (NPC) receiving radiation therapy alone had noninferior oncologic outcomes and fewer acute adverse events, compared with those receiving concurrent chemoradiotherapy (CCRT). We have several comments about this impactful study.…”

“…However, eTable 7 in Supplement 2 of the present study showed that 76.31% of the patients in the IC-CCRT group received 6 cycles (weekly 30 mg/m 2 per cycle) of cisplatin in CCRT, and the mean cumulative dose of cisplatin in CCRT was 171 mg/m 2 . Since the cumulative dose of cisplatin in CCRT was demonstrated to be prognostic for NPC, with a cut off of 200 mg/m 2 for significantly different overall survival, the less intensive cisplatin dose in CCRT might make it easier to report significant results in this noninferiority study.…”

Chemotherapy, Radiation Therapy, and Nasopharyngeal Carcinoma

“…To the Editor We read the article by Dai et al with great interest. Omitting chemotherapy in patients receiving induction chemotherapy (IC) is a hot topic in nasopharyngeal carcinoma treatment, particularly in the intensity-modulated radiotherapy era.…”

Chemotherapy, Radiation Therapy, and Nasopharyngeal Carcinoma—Reply

“…In Reply We appreciate the comments made by Lee et al and Bayatfard et al on our recent article . We applied concurrent cisplatin in the conventional 30-mg/m 2 dose weekly when we designed this trial.…”