A randomized phase 3 trial comparing nimotuzumab plus cisplatin chemoradiotherapy versus cisplatin chemoradiotherapy alone in locally advanced head and neck cancer

Abstract

BACKGROUND:Because the addition of nimotuzumab to chemoradiation in patients with locally advanced head and neck cancer improved outcomes in a phase 2 study, the authors conducted a phase 3 study to confirm these findings. METHODS: This openlabel, investigator-initiated, phase 3, randomized trial was conducted from 2012 to 2018. Adult patients with locally advanced head and neck cancer who were fit for radical chemoradiation were randomized 1:1 to receive either radical radiotherapy (66-70 grays) with concurrent weekly cisplatin (30 mg/m 2 ) (CRT) or the same schedule of CRT with weekly nimotuzumab (200 mg) (NCRT). The primary endpoint was progression-free survival (PFS); key secondary endpoints were disease-free survival (DFS), duration of locoregional control (LRC), and overall survival (OS). An intent-to-treat analysis also was performed. RESULTS: In total, 536 patients were allocated equally to both treatment arms. The median follow-up was 39.13 months. The addition of nimotuzumab improved PFS (hazard ratio [HR], 0.69; 95% CI, 0.53-0.89; P = .004), LRC (HR, 0.67; 95% CI, 0.50-0.89; P = .006), and DFS (HR, 0.71; 95% CI, 0.55-0.92; P = .008) and had a trend toward improved OS (HR, 0.84; 95% CI, 0.65-1.08; P = .163). Grade 3 through 5 adverse events were similar between the 2 arms, except for a higher incidence of mucositis in the NCRT arm (66.7% vs 55.8%; P = .01). CONCLUSIONS: The addition of nimotuzumab to concurrent weekly CRT improves PFS, LRC, and DFS. This combination provides a novel alternative therapeutic option to a 3-weekly schedule of 100 mg/m 2 cisplatin in patients with locally advanced head and neck cancer who are treated with radical-intent CRT. Cancer 2019;125:3184-3197.

Nimotuzumab plus platinum-based chemotherapy versus platinum-based chemotherapy alone in patients with recurrent or metastatic nasopharyngeal carcinoma

“… 19 A randomized phase III trial compared NTZ plus cisplatin and RT versus cisplatin and RT in locally advanced HNSCC, and also showed that the addition of NTZ improved PFS, LRC, DFS, and had a trend toward improved OS. 20 Both studies mentioned previously revealed that CTX or NTZ adds additional anti-tumor efficacy, thereby resulting in improved efficacy, which is similar to our findings. NTZ is biologically and molecularly different from CTX, 21 although they have similar mechanisms, NTZ inhibits both ligand-dependent and ligand-independent signaling of the EGFR pathway.…”

Nimotuzumab-cisplatin-radiation versus cisplatin-radiation in HPV negative oropharyngeal cancer

“…Addition of nimotuzumab as a radiosensitizer to weekly cisplatin and addition of cetuximab to carboplatin 5-FU resulted in an improvement in outcomes over weekly cisplatin and carboplatin-5 FU in locally advanced head and neck cancers [7,9]. However, a similar study of the addition of cetuximab to 3 weekly cisplatin was associated with negative results [8].…”

“…The study protocol was approved by the institutional ethics committee and the study was conducted in accordance with national (Indian Council of Medical Research) and international guidelines (Good Clinical Practice and Declaration of Helsinki) on human research. The detailed inclusion-exclusion criteria with study protocol are already published [7]. The study enrolled patients with locally advanced head and neck cancer who were planned for curative intent therapy, had normal organ functions, no uncontrolled comorbidities and ECOG PS 0-2.…”

“…Recently a phase 3 randomized study was reported by us, in locally advanced head and neck cancers, testing the role of concurrent nimotuzumab in addition to weekly cisplatin and definitive radiation. The study met its primary endpoint of progression-free survival [7]. However, a similar study exploring the role of Cetuximab (RTOG 0522) was negative [8].…”

“…We had hypothesized that an improvement in outcomes in our study was seen due to the differential patient population in our study when compared to the RTOG 0552 study. We had a younger cohort of patients and a predominantly HPV negative disease [7]. This population, even in RTOG 0522 showed a trend towards improvement with the addition of cetuximab [8].…”