title: Nimotuzumab provides survival benefit to patients with inoperable advanced squamous cell carcinoma of the head and neck: a randomized, open-label, phase IIb, 5-year study in Indian patients.
abstract: OBJECTIVE
  Overexpression of epidermal growth factor receptor (EGFR) in many cancers makes it an attractive therapeutic target. This study evaluated the clinical utility of nimotuzumab, a monoclonal anti-EGFR antibody, used concurrently with radiotherapy (RT) and chemoradiotherapy (CRT) in squamous cell carcinoma of the head and neck (SCCHN).
  
  
  METHODS
  This open-label study randomized 92 treatment-naïve patients (1:1) with advanced SCCHN into chemoradiation (CRT ± nimotuzumab) or radiation (RT ± nimotuzumab) group by investigator's discretion; these were further randomized into CRT + nimotuzumab or CRT and RT + nimotuzumab or RT groups, respectively. Treatment included 6 cycles each of cisplatin (50 mg/week), nimotuzumab (200 mg/week), and RT (total dose, 60-66 Gy). Response (tumor size reduction) was assessed at Month 6 post-treatment and survival, at Month 60.
  
  
  RESULTS
  Forty and 36 patients in the chemoradiation and radiation groups, respectively (intent-to-treat population) were evaluated. Overall response at Month 6 post-treatment was 100% with CRT + nimotuzumab, 70% with CRT, 76% with RT + nimotuzumab, and 37% with RT. At Month 60, overall survival was 57% with CRT + nimotuzumab, 26% with CRT (P = 0.03), 39% with RT + nimotuzumab, and 26% with RT (P > 0.05). Median overall survival was not reached for CRT + nimotuzumab; it was 21.94 months for CRT (P = 0.0078), 14.36 months for RT + nimotuzumab, and 12.78 months for RT (P = 0.45). Risk of death was 64% lower with CRT + nimotuzumab than with CRT (95%CI: 0.37, 1.56), and 24% lower with RT + nimotuzumab than with RT (95%CI: 0.16, 0.79). Thus nimotuzumab was safe and well tolerated with few mild to moderate self-limiting adverse events.
  
  
  CONCLUSIONS
  Concurrent use of nimotuzumab with CRT/RT is safe and provides long-term survival benefit.
authors.affiliation: Kidwai Memorial Institute of Oncology, Bangalore, India.
authors.forename: B K M
authors.initials: BK
authors.lastname: Reddy
authors.affiliation: Kidwai Memorial Institute of Oncology, Bangalore, India. Electronic address: lokeshv2013@gmail.com.
authors.forename: V
authors.initials: V
authors.lastname: Lokesh
authors.affiliation: Shirdi Sai Baba Cancer Hospital, Manipal, India.
authors.forename: M S
authors.initials: MS
authors.lastname: Vidyasagar
authors.affiliation: Kasturba Medical College Hospital, Mangalore, India.
authors.forename: K
authors.initials: K
authors.lastname: Shenoy
authors.affiliation: Kidwai Memorial Institute of Oncology, Bangalore, India.
authors.forename: K G
authors.initials: KG
authors.lastname: Babu
authors.affiliation: Kidwai Memorial Institute of Oncology, Bangalore, India.
authors.forename: A
authors.initials: A
authors.lastname: Shenoy
authors.affiliation: Kidwai Memorial Institute of Oncology, Bangalore, India.
authors.forename: T
authors.initials: T
authors.lastname: Naveen
authors.affiliation: Kidwai Memorial Institute of Oncology, Bangalore, India.
authors.forename: Bindhu
authors.initials: B
authors.lastname: Joseph
authors.affiliation: Kidwai Memorial Institute of Oncology, Bangalore, India.
authors.forename: R
authors.initials: R
authors.lastname: Bonanthaya
authors.affiliation: Kidwai Memorial Institute of Oncology, Bangalore, India.
authors.lastname: Nanjundappa
authors.affiliation: Kidwai Memorial Institute of Oncology, Bangalore, India.
authors.forename: P P
authors.initials: PP
authors.lastname: Bapsy
authors.affiliation: Kidwai Memorial Institute of Oncology, Bangalore, India.
authors.lastname: Loknatha
authors.affiliation: Kasturba Medical College Hospital, Mangalore, India.
authors.forename: Jayarama
authors.initials: J
authors.lastname: Shetty
authors.affiliation: Kasturba Medical College Hospital, Mangalore, India.
authors.forename: Krishna
authors.initials: K
authors.lastname: Prasad
authors.affiliation: Kidwai Memorial Institute of Oncology, Bangalore, India.
authors.forename: C R
authors.initials: CR
authors.lastname: Tanvir Pasha
mesh_terms: D000328:Adult; D000368:Aged; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000378:metabolism / Q000532:radiotherapy; D003131:Combined Modality Therapy; D066246:ErbB Receptors / Q000378:metabolism; D005260:Female; D006258:Head and Neck Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000532:radiotherapy; D006801:Humans; D008297:Male; D008875:Middle Aged; D016019:Survival Analysis
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; C501466:nimotuzumab; D066246:ErbB Receptors
keywords: Chemoradiation; Epidermal growth factor receptor; Head and neck cancer; Humanized monoclonal antibody; Nimotuzumab