Phase II study of nimotuzumab (TheraCim‐hR3) concurrent with cisplatin/radiotherapy in patients with locally advanced head and neck squamous cell carcinoma

Abstract

Background The efficacy of a combination of nimotuzumab, a humanized monoclonal antibody to the epidermal growth factor receptor, with chemoradiation in locally advanced head and neck squamous cell carcinoma (HNSCC) was evaluated in a phase II study. Methods Patients with stage III/IV HNSCC received 3‐weekly cisplatin 100 mg/m2 for three cycles and weekly nimotuzumab 200 mg for 8 weeks concurrently with radiotherapy. Primary endpoint was best overall response (BOR) and secondary endpoint was progression‐free survival (PFS). Results Thirty‐seven patients were included; the majority were Chinese (76%), male (89%), and had stage IVA/IVB HNSCC (92%). BOR of complete and partial response was seen in 22/37 (59%) and 10/37 (27%) patients, respectively. Median PFS was 17.5 months (95% CI: 11.1–54.5) and 3‐year PFS was 40.4% (95% CI: 24.3–55.9). The frequency and type of adverse events observed were similar to standard chemoradiation. Conclusion The combination of nimotuzumab with cisplatin and radiotherapy was safe and achieved high response rates in HNSCC.

Recent findings on the impact of ErbB receptors status on prognosis and therapy of head and neck squamous cell carcinoma

“…In this regard, a modest efficacy in terms of clinical outcomes has been reported for the fully human anti-EGFR antibodies Panitumumab and Zalutumumab, and for Duligotuzumab, a dual-action antibody directed against EGFR and ErbB3 ( 115 ). Among the anti-EGFR therapeutic antibodies, some encouraging results have instead been obtained with Nimotuzumab, whose binding requires that EGFR is expressed at high density on the surface of the target cells, thus resulting in selective activity on EGFR-overexpressing tumor cells as compared to normal cells ( 115 , 121 ). As for ErbB receptors TKIs, Gefitinib and Erlotinib, which act as reversible inhibitors of EGFR, and Lapatinib, a reversible inhibitor of both EGFR and ErbB2, have also shown a modest activity in HNSCC patients ( 1 , 115 ).…”

Combination Therapy as a Promising Way to Fight Oral Cancer

“…Consequently, this limitation may contribute to the observed absence of correlation between EGFR expression levels and the response to EGFR-targeting therapies [ 114 ]. mAbs targeting EGFR have been reported to induce NK-dependent ADCC, while activating CD8+ T-cell responses [ 115 , 116 ]. Therefore, it is suggested that low levels of lymphocytes can have an impact on mAbs efficacy.…”

Shooting at Moving and Hidden Targets—Tumour Cell Plasticity and the Notch Signalling Pathway in Head and Neck Squamous Cell Carcinomas

“…A number of additional anti-EGFR antibodies have been recently developed and clinically tested, such as Panitumumab [ 142 , 143 , 144 ], Nimotuzumab [ 145 , 146 , 147 ], and Sym004 [ 148 , 149 ]. The anti-EGFR antibody Panitumumab was shown moderate activity as a single agent in HNSCC patients, previously treated with platinum-based drugs [ 142 ].…”

“…The anti-EGFR antibody Panitumumab was shown moderate activity as a single agent in HNSCC patients, previously treated with platinum-based drugs [ 142 ]. The benefits of adding Nimotuzumab to combination therapy with cisplatin and radiotherapy have been reported in some HNSCC patients [ 146 ], and high HIF1α (hypoxia-inducible factor 1-alpha) expression may indicate likely benefit for such treatments [ 145 ]. Sym004 has been in development for at least 10 years, and represents a mix of two chimeric monoclonal antibodies [ 150 ].…”