Radiotherapy plus nimotuzumab versus cisplatin in low-risk locoregionally advanced nasopharyngeal carcinoma who had favorable response to induction chemotherapy: A randomised, phase III, non-inferiority trial.

Abstract

6078 Background: Patients with low-risk locoregionally advanced nasopharyngeal carcinoma (LA-NPC) have high survival when treated with radiotherapy (RT) plus cisplatin after induction chemotherapy (IC). Whether replacement of cisplatin with nimotuzumab—a humanized antibody against the epidermal growth factor receptor (EGFR)—can preserve high survival and reduce treatment toxicity is unknown for patients with good response to IC. Therefore, we assessed whether nimotuzumab plus RT was non-inferior to cisplatin plus RT in low-risk LA-NPC with favorable response to IC. Methods: The study was a randomised, non-inferiority, phase 3 trial at Sun Yat-sen University Cancer Centre, China. Adult patients (aged 18–70 years) with non-keratinizing stage II-IVA (except N3 category; the eighth edition of the American Joint Committee on Cancer classification system) NPC, with pre-treatment plasma EBV DNA<1500 copies/mL, positive EGFR expression and an Eastern Cooperative Oncology Group performance status of 0–1, were treated with 2 cycles of paclitaxel-cisplatin-fluorouracil IC, those achieved CR/PR with undetectable EBV DNA were randomly assigned (1:1) to receive either intravenous nimotuzumab at a dose of 200 mg weekly or cisplatin 100 mg/m² on days 1, 22 and 43 of intensity-modulated radiotherapy. Randomization was done using a computer-generated code random number code with a block size of six, stratified by overall stage. The primary endpoint was 2-year progression-free survival (PFS) in the intention-to-treat population. Safety was assessed in all participants who received at least one dose of the assigned treatment. This study is registered with ClinicalTrials.gov, number NCT 04456322. Results: Of the 381 patients who underwent randomization, 191 were assigned to RT plus nimotuzumab and 190 to RT plus cisplatin. After median follow-up duration of 39.5 months, in the evaluation of 2-year PFS, RT plus nimotuzumab was noninferior to RT plus cisplatin (94.2% and 95.8%, respectively; absolute difference, 1.6 percentage points; 95% CI, –2.8 to 6.0, [noninferiority margin, -10 percentage points], P noninferiority =0.0001). The most common grade 3-4 acute toxicities were leucopenia (37 [19.5%] of 190 patients in the cisplatin group vs. 2 [1.1%] of 189 patients in the nimotuzumab group), mucositis (36 [18.9%] vs. 28 [14.8%]), and vomiting (21 [11.1%] vs. 0). No patients died during treatment. Patients in the cisplatin group also showed more grade 1-2 auditory or hearing loss and peripheral neuropathy in late adverse events, and impaired long-term quality of life. Conclusions: Our findings show that nimotuzumab plus RT represents an alternative concurrent treatment strategy for patients with low-risk LA-NPC with a favorable response to IC. Clinical trial information: NCT04456322 .