An open-label, randomized, study of h-R3mAb (nimotuzumab) in patients with advanced (stage III or IVa) squamous cell carcinoma of head and neck (SCCHN): Four-year survival results from a phase IIb study.

Abstract

5530 Background: h-R3mAb (nimotuzumab) is a humanized monoclonal antibody targeting epidermal growth factor receptor (EGFR). EGFR is over-expressed in >90% squamous cell carcinoma of head and neck (SCCHN). Patients with advanced inoperable SCCHN have poor outcome to radiotherapy (RT) or chemoradiotherapy (CRT) treatment alone. Adding biologically active targeted therapies to RT/CRT might further improve therapeutic outcome with minimal morbidity. Methods: Total of 113 patients with (stage III or IVa), inoperable SCCHN were screened; 92 randomized in 1:1 ratio in two groups; group A received [RT Vs RT+h-R3mAb] and group B received [CRT vs. CRT+h-R3mAb]. Treatment included radiotherapy in total dose 60 -66Gy, h-R3mAb 200mg by I.V infusion over 60 min/ week for 6weeks and in group B, chemotherapy CDDP 50mg/week for 6weeks. Results: Seventy-six patients were evaluable; 36-groupA and 40-groupB. Locoregional response was 100% in CRT+h-R3mAb vs. 70% in CRT and 76% in RT+h-R3mAb vs. 37% in RT. At 48 months follow-up; Overall survival rate (ITT) was 47% in (CRT+h- R3mAb) vs. 21% (CRT)(p = 0.01) and 34% (RT+h-R3mAb)vs. 13%(RT)(NS), median overall survival was NR* for (CRT+h-R3mAb) vs. 21.9 months (CRT)(HR-0.35, P-0.01) and 14.3months (RT+h-R3mAb) vs. 12.7months (RT)(HR-0.74, P-0.42). The subjects alive in CRT+h-R3mAb arm had mean EGFR values of 67.5%. There was no statistically significant difference in mean EGFR % with respect to survival of alive and deceased in this population. Adding h-R3mAb to Chemoradiation resulted in significant reduction in risk of death by 65 % (HR 0.35, p-0.01). Conclusions: Concurrent use of h-R3mAb with RT/CRT is safe and efficacious; it enhanced locoregional control and survival on long term follow-up. This is the first randomized study demonstrating clinical benefit from EGFR-targeting mAb in the absence of the advanced toxicities due to its distinguished property of preferentially targeting the tumor. The encouraging efficacy data recommends further development of CRT+h-R3mAb paradigm in treatment of SCCHN. No significant financial relationships to disclose.