Radiation Plus Concurrent Nimotuzumab Versus Cisplatin-Based Chemotherapy in Locally Advanced Nasopharyngeal Cancer: An Interim Analysis of a Phase 3 Randomized Clinical Trial

Purpose/Objective(s)Concurrent chemoradiation is the standard treatment for locoregionally advanced nasopharyngeal cancer (NPC). However, concurrent chemotherapy usually produces side-effects that limit its use. Nimotuzumab is a novel humanized monoclonal antibody. Its use with radiation therapy (RT) for locoregionally advanced NPC was approved by the Chinese FDA and further recommended by the Chinese National Comprehensive Cancer Network as one of the standard treatment options. Thus, we initiated a phase 3 randomized trial aimed at studying the toxicity and effectiveness of nimotuzumab versus cisplatin chemotherapy used in concurrence with intensity modulated RT (IMRT). Here we report the results of an interim analysis with a focus on the acute treatment-induced adverse effects.Materials/MethodsPatients with newly diagnosed Stage III-IVB NPC were randomly assigned to nimotuzumab (200 mg/week for 8 week starting 1 week before IMRT) or cisplatin (40 mg/m2/week) concurrently given with IMRT to 70 Gy in 35 fractions after neoadjuvant chemotherapy consisting of docetaxel, cisplatin, and 5-FU (TPF-regimen). The primary endpoint was treatment-induced acute moderate-to-severe mucositis or dermatitis. Planned accrual for each arm was 160 patients.ResultsBetween July 2012 and Nov 2014, 135 patients who were randomly assigned to IMRT plus cisplatin (75 cases) or nimotuzumab (60 cases) were included in this analysis. Grade 3–4 mucositis or dermatitis during RT were higher in the concurrent chemotherapy group as compared to the nimotuzumab group: Grade 1, Grade 2, and Grade 3-4 were observed in 40.0%, 35.0%, and 25.0% of patients in the nimotuzumab arm versus 26.7%, 36.0%, and 37.3% in the cisplatin arm (P = .126). The Grade 3–4 GI toxicities and Grade 2–4 hematologic toxicities during RT were significantly higher with cisplatin as compared to the nimotuzumab (P < .05). The number of patients who finished at least 5 planned courses of concurrent cisplatin chemotherapy and 8 planned courses of nimotuzumab were 31 (41.3%) and 59 (98.3%), respectively (P = .000). The CR rate of primary tumor and lymph node metastasis was 92.0% and 96.9% in the cisplatin arm versus 95.0% and 92.3% in the nimotuzumab arm (P = NS). Ten patients (16.7%) in the nimotuzumab group and 9 patients (12.0%) in the cisplatin group had treatment failure (P = .438). at the time of this analysis. One patient treated with cisplatin died from distant metastasis.ConclusionConcurrent IMRT with nimotuzumab or cisplatin following TPF-based induction chemotherapy produced similar short-term outcomes in terms of response. Acute toxicity profile is better in the nimotuzumab group. Purpose/Objective(s)Concurrent chemoradiation is the standard treatment for locoregionally advanced nasopharyngeal cancer (NPC). However, concurrent chemotherapy usually produces side-effects that limit its use. Nimotuzumab is a novel humanized monoclonal antibody. Its use with radiation therapy (RT) for locoregionally advanced NPC was approved by the Chinese FDA and further recommended by the Chinese National Comprehensive Cancer Network as one of the standard treatment options. Thus, we initiated a phase 3 randomized trial aimed at studying the toxicity and effectiveness of nimotuzumab versus cisplatin chemotherapy used in concurrence with intensity modulated RT (IMRT). Here we report the results of an interim analysis with a focus on the acute treatment-induced adverse effects. Concurrent chemoradiation is the standard treatment for locoregionally advanced nasopharyngeal cancer (NPC). However, concurrent chemotherapy usually produces side-effects that limit its use. Nimotuzumab is a novel humanized monoclonal antibody. Its use with radiation therapy (RT) for locoregionally advanced NPC was approved by the Chinese FDA and further recommended by the Chinese National Comprehensive Cancer Network as one of the standard treatment options. Thus, we initiated a phase 3 randomized trial aimed at studying the toxicity and effectiveness of nimotuzumab versus cisplatin chemotherapy used in concurrence with intensity modulated RT (IMRT). Here we report the results of an interim analysis with a focus on the acute treatment-induced adverse effects. Materials/MethodsPatients with newly diagnosed Stage III-IVB NPC were randomly assigned to nimotuzumab (200 mg/week for 8 week starting 1 week before IMRT) or cisplatin (40 mg/m2/week) concurrently given with IMRT to 70 Gy in 35 fractions after neoadjuvant chemotherapy consisting of docetaxel, cisplatin, and 5-FU (TPF-regimen). The primary endpoint was treatment-induced acute moderate-to-severe mucositis or dermatitis. Planned accrual for each arm was 160 patients. Patients with newly diagnosed Stage III-IVB NPC were randomly assigned to nimotuzumab (200 mg/week for 8 week starting 1 week before IMRT) or cisplatin (40 mg/m2/week) concurrently given with IMRT to 70 Gy in 35 fractions after neoadjuvant chemotherapy consisting of docetaxel, cisplatin, and 5-FU (TPF-regimen). The primary endpoint was treatment-induced acute moderate-to-severe mucositis or dermatitis. Planned accrual for each arm was 160 patients. ResultsBetween July 2012 and Nov 2014, 135 patients who were randomly assigned to IMRT plus cisplatin (75 cases) or nimotuzumab (60 cases) were included in this analysis. Grade 3–4 mucositis or dermatitis during RT were higher in the concurrent chemotherapy group as compared to the nimotuzumab group: Grade 1, Grade 2, and Grade 3-4 were observed in 40.0%, 35.0%, and 25.0% of patients in the nimotuzumab arm versus 26.7%, 36.0%, and 37.3% in the cisplatin arm (P = .126). The Grade 3–4 GI toxicities and Grade 2–4 hematologic toxicities during RT were significantly higher with cisplatin as compared to the nimotuzumab (P < .05). The number of patients who finished at least 5 planned courses of concurrent cisplatin chemotherapy and 8 planned courses of nimotuzumab were 31 (41.3%) and 59 (98.3%), respectively (P = .000). The CR rate of primary tumor and lymph node metastasis was 92.0% and 96.9% in the cisplatin arm versus 95.0% and 92.3% in the nimotuzumab arm (P = NS). Ten patients (16.7%) in the nimotuzumab group and 9 patients (12.0%) in the cisplatin group had treatment failure (P = .438). at the time of this analysis. One patient treated with cisplatin died from distant metastasis. Between July 2012 and Nov 2014, 135 patients who were randomly assigned to IMRT plus cisplatin (75 cases) or nimotuzumab (60 cases) were included in this analysis. Grade 3–4 mucositis or dermatitis during RT were higher in the concurrent chemotherapy group as compared to the nimotuzumab group: Grade 1, Grade 2, and Grade 3-4 were observed in 40.0%, 35.0%, and 25.0% of patients in the nimotuzumab arm versus 26.7%, 36.0%, and 37.3% in the cisplatin arm (P = .126). The Grade 3–4 GI toxicities and Grade 2–4 hematologic toxicities during RT were significantly higher with cisplatin as compared to the nimotuzumab (P < .05). The number of patients who finished at least 5 planned courses of concurrent cisplatin chemotherapy and 8 planned courses of nimotuzumab were 31 (41.3%) and 59 (98.3%), respectively (P = .000). The CR rate of primary tumor and lymph node metastasis was 92.0% and 96.9% in the cisplatin arm versus 95.0% and 92.3% in the nimotuzumab arm (P = NS). Ten patients (16.7%) in the nimotuzumab group and 9 patients (12.0%) in the cisplatin group had treatment failure (P = .438). at the time of this analysis. One patient treated with cisplatin died from distant metastasis. ConclusionConcurrent IMRT with nimotuzumab or cisplatin following TPF-based induction chemotherapy produced similar short-term outcomes in terms of response. Acute toxicity profile is better in the nimotuzumab group. Concurrent IMRT with nimotuzumab or cisplatin following TPF-based induction chemotherapy produced similar short-term outcomes in terms of response. Acute toxicity profile is better in the nimotuzumab group.