ESMO @ ECC 2013: No Benefit Seen from Adding Zalutumumab to Radiotherapy in Patients with Squamous Cell Carcinoma of the Head and Neck

Addition of EGFR inhibitor, zalutumumab, did not increase loco-regional control nor disease-specific or overall survival.

Concomitant EGFR inhibitor zalutumumab plus primary (chemo-)radiotherapy and nimorazole did not show benefit over primary (chemo-)radiotherapy and nimorazole for the treatment of patients with head and neck squamous cell carcinoma (HNSCC) and neither improved loco-regional control nor disease-specific or overall survival at 3 years.

First results of a randomised phase III study were reported 30 September, 2013 by Dr. Jesper Eriksen of the Department of Oncology, Odense University Hospital, Odense, Denmark during the Best and Late Breaking Abstracts section of Presidential Session III (Abstract E17-7116) at the 17th ECCO – 38th ESMO – 32nd ESTRO European Cancer Congress. The European Cancer Congresses are organised in joint partnership with ESSO, EACR, EONS and SIOPE as a forum for the latest in oncology research and to offer multidisciplinary and multi-professional educational opportunities in oncology. The 2013 Congress convened in Amsterdam, The Netherlands from 27 September until 1 October.

Design of phase III DAHANCA-9 trial

The DAHANCA-9 phase III trial (NCT00496652) was conducted by the Danish Head and Neck Cancer Group (DAHANCA). The trial evaluated whether the addition of zalutumumab, a fully humanised IgG1 monoclonal antibody directed towards the Epidermal Growth Factor receptor (EGFR) to concurrent radiotherapy could improve outcome in patients with HNSCC.

The trial enrolled 619 patients with biopsy-verified HNSCC from November 2007 to June 2012. Patients were stratified by tumour-site, stage, p16 status and concurrent cisplatin. The tumour site was the oral cavity in 4% of patients, oropharynx in 69%, hypopharynx in 12% and larynx in 14% of patients. Stage 3-4 disease was confirmed in 554 (89%) patients and 75% of the oropharyngeal carcinomas were positive for p16. In all, 70% of patients were receiving concurrent cisplatin; patients with stage 3-4 carcinomas received weekly cisplatin at 40 mg/m2 during radiotherapy.

Patients were randomised to receive either sole radiotherapy (control arm, n=309) or radiotherapy plus zalutumumab at 8 mg/kg (zalutumumab arm, n=310). Patients in the zalutumumab arm received the first dose the week prior to beginning radiotherapy and continued to receive it weekly during irradiation. Patient and tumour characteristics were well balanced between arms. Radiotherapy was the same in both arms: primary accelerated radiotherapy predominantly 66-68Gy, 2Gy/fx, 6fx/wk and concomitant daily hypoxic radiosensitisation with nimorazole. Elective neck dissection was not performed.

The trial’s primary endpoint was loco-regional control (LRC) and secondary endpoints included disease-specific survival (DSS) and overall survival (OS).

The study results

At time of final data collection for primary outcome measure (July 2013), the median observation time was 36 month (range12 - 67 months). Data analysis showed 126 verified cases of LRC, 71 patients were dead of HNNSC and 45 had died of other causes.

 

No difference was demonstrated between arms in the rate of LRC at three years; the 3-year LRC rate was 78% in the zalutumumab arm compared to 79% in the control arm, (hazard ratio [HR] 0.8; 95% confidence interval [CI] 0.6, 1.2). Similar results of comparable response between arms were seen for disease-free and overall survival; DSS (HR 1.0; 95% CI 0.7, 1.7) and OS (HR 0.9; 95% CI 0.6, 1.3). The effect of zalutumumab was not influenced by p-16 positivity HR (1.0; 95% CI 0.6, 1.8) nor by p-16 negativity (HR 0.8; 95% CI 0.5, 1.4).

Treatment was generally well tolerated. However, nearly all (94%) of patients in the zalutumumab arm reported a skin rash, with 29% of these patients experiencing a grade 3-4 rash. Zalutumumab was halted by 13% of patients due to rash.

These results represent the first report of data from this randomised phase III and additional analyses are underway.

No conflict of interest was reported.

No Benefit Seen from Adding Zalutumumab to Radiotherapy in Patients with Squamous Cell Carcinoma of the Head and Neck
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