HEAD & NECK CANCER

Locally-advanced Squamous Cell Carcinoma Head And Neck Cancer

Nimotuzumab has been studied in 8 clinical trials in Head and Neck indications involving a total of 667 patients in Canada, Cuba and India. There are ongoing 5 studies now in Singapore, Saudi Arabia, Philippine, Thailand, Australia, India and other countries involving more than 712 patients as of August 2018.

For a complete list of nimotuzumab publications and ongoing studies in Head an Neck indications please contact us here.

Below is an excerpt of one of nimotuzumab studies conducted in India:

Reddy, B. K. M. et al. 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. Oral Oncol. 50, 498–505 (2014).

 

Disease state

Tumors arising from the head and neck are the seventh most common neoplasms worldwide. In 2010, an estimate of 634 760 new cases were diagnosed and 356 705 deaths occurred secondary to these tumors globally.

The vast majority of head and neck malignancies (95%), both worldwide and in Europe, are squamous cell carcinomas (SCCHN) by histology
More than 60% of SCCHN are diagnosed at a localized or locally advanced stage which, by and large, portends a curable prognosis.

The current standard treatment for patients with unresectable locally advanced head and neck cancer is concurrent cisplatin based chemoradiation*. This line therapy gives absolute improvement in 5-year survival ranges between 5% and 9%.

There are growing concerns related to distant metastases and the late toxicity induced by chemoradiation among the long-term survivors.

*Based on tumor-related factors, such as primary site and stage, as well as patient-related characteristics, such as age, performance status and pre-existent comorbidities.

 

Study Design

Head Neck Cancer Study Design

This is an open-label, randomized, multicenter, controlled clinical trial that compared nimotuzumab and radiotherapy versus radiotherapy alone and nimotuzumab, radiotherapy and cisplatin versus radiotherapy and cisplatin only.

The inclusion criteria include:

  • Stage III or IV SCCHN IVA (T1-T4a, No.N2)
  • 18-70 years old
  • Karnofsky performance score ≥ 60
  • The treatments were given as the following:

Radiotherapy : 60-66 Gy , 5 days a week, for 6 to 6.5 weeks

  • Cisplatin: 50 mg on day-1 each week, for 6 weeks
  • Nimotuzumab: 200 mg on day 1 (for chemoradiotherapy group) or day 4 (radiotherapy group) every week, for 6 weeks

Primary endpoint was response (tumor size reduction) rate at 6 months.

Secondary endpoints included overall survival, progression free survival, at 6 months and 60 months.

 

Nimotuzumab gives a better response rate and improved survival rate at year-5

  • At least 7 out of 10 patients receiving nimotuzumab concomitantly with radiotherapy had reduced tumour size, while tumour size reduction was seen in all patients receiving nimutozumab and concurrent chemoradiotherapy.
  • 5-Year survival rates were significantly increase in patients treated with nimotuzumab by 13% and 31% in radiotherapy group and chemoradiotherapy group, respectively.

Head Neck Cancer Survival Rate*NR: Not reached yet; RT: Radiotherapy; CRT: Chemoradiotherapy

 

Efficacy results:

  • 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 rate 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).
    Nimotuzumab + Cisplatin + RT improved median OS at 5 years compared to cisplatin and RT alone.

 

Nimotuzumab offers extended overall survival

Head Neck Cancer Overall Survival

Addition of nimotuzumab reduces death risk up to 48% and the patients receiving nimotuzumab showed better overall survival than those without nimotuzumab:

  • CRT/RT + nimo group (n= 46) : 49.38 months
  • CRT/RT group (n= 46) : 16.36

(0.52, 95% CI: 0.30, 0.89; P = 0.012)

Nimotuzumab is safe and well-tolerated  for patients with SCCHN

Percentage Grade 3 Adverse

  • Skin rash was observed only in 6.5% of the patients, which is quite low compared to that of other EGFR inhibitor (60-80%).
  • Adverse events that are related to nimotuzumab included asthenia (grade 1/2), dizziness, hematuria (microscopic), vomiting, loose stools, fever, chills, pruritus, urticaria/rash, headache, hypertension, and fluctuation in blood pressure.
  • No drug-related death nor long term drug-related toxicities were observed on the 65-month follow up.