Cetuximab With Chemoradiation Worse Than Chemoradiation Alone in Older Patients With HNSCC

Treatment with cetuximab (CX), concurrent with chemoradiation (CRT), in older patients diagnosed with head and neck squamous cell carcinoma (HNSCC) has similar toxicity as CRT treatment, but overall survival (OS) is inferior. These are the results of a retrospective analysis that was presented at the 2018 American Society of Clinical Oncology Annual Meeting, June 1-5, in Chicago, Illinois.

Cetuximab, a monoclonal antibody that inhibits the epidermal growth factor receptor, was approved in 2006 for the treatment of metastatic colorectal cancer and local or advanced HNSCC (in combination with chemoradiation) as well as metastatic HNSCC.

The antibody has been increasingly used in older patients with HNSCC as a radiosensitizer for chemoradiation treatment. “However, overall survival after definitive CRT-CX, compared with definitive CRT, has not been adequately evaluated outside of younger more highly selected clinical-trial populations with locally advanced HNSCC,” said Dan Paul Zandberg, MD, University of Maryland, Marlene and Stewart Greenebaum Comprehensive Cancer Center, who presented the results of the study.

For their study, the authors used the Surveillance Epidemiology and End Results (SEER) cancer registry programs data that were linked with the Medicare database to evaluate OS in patients with HNSCC diagnosed between 2005-2011.

Inclusion criteria included individuals who had continuous Medicare Part A and B coverage. Patients on a health maintenance organization plan during the 12 months prior to their diagnosis were excluded. Additionally, inclusion in the study required access to complete claims for at least a year after diagnosis, primary treatment should have been radiation treatment (RT) alone or chemoradiation.

Enforcement of the inclusion/exclusion criteria identified 2135 beneficiaries, majority male (73.5%), with a median age of 73 years (range, 66-104). Primary subsites of disease in these patients were oropharynx (OP, 61%), hypopharynx (HP, 15%), nasopharynx (5%), and larynx (19%). Eighty-two percent of patients received platinum-based chemotherapy, of which 52% received cisplatin.

The authors found that OS in the CRT-CX—treated patients was worse than those who received CRT (P <.005) and similar to RT (P = .21): 5-year OS was 46% for CRT, 35% for CRT-CX, and 32% for RT. The median survival was 4.5 years (range, 3.8-4.9), 2.5 years (range, 2.2-3.0), and 2.2 years (range, 2.0-3.0) years in the CRT, CRT-CX, and RT populations, respectively. The risk of death was greater with CRT-CX compared to CRT (hazard ratio, 1.41 [range, 1.24- 1.61]; P = 0.0001), after stratifying by stage and primary site, and adjusting for gender, race, age, income, Charlson comorbidity index, marital status, hospital type, and year of diagnosis.

In the context of the primary site, a similar trend was observed; 5-year OS in patients with OP was highest with CRT-treated patients (54%; median OS, 5.59 years) compared with CRT-CX (39%; median OS 2.95 years) and RT (34%; median OS 2.24 years). In patients with HP, 5-year OS was 34%, 22%, and 26% in CRT, CRT-CX, and RT groups, respectively.

However, CRT led to a significantly higher rate of hearing loss within the first 3 months of treatment compared to CRT-CX (9.3% vs. 4.1%, P <.001); dysphagia, gastrostomy tube placement, pneumonia, and weight loss occurred at similar rates between the 2 treatment groups over the first 12 months after diagnosis.

“Analysis of real-world data and the large patient numbers are the strengths of our retrospective study,” Zandberg said. He acknowledged, however, that their research group was unable to obtain data on performance status, overall frailty, and severity of comorbidities in the patient population.

Zandberg concluded that definitive treatment with CRT-CX was associated with inferior OS compared to CRT even after adjustment for established prognostic factors, and with similar toxicity, in the SEER-Medicare patient population. “Our data suggest that non-cetuximab based chemoradiation should be used for eligible older HNSCC patients,” he said.

Cisplatin remains the standard-of-care for concurrent therapy with radiation, with CX as an option in patients who cannot tolerate cisplatin.

Reference

Zandberg DP, Cullen KJ, Varki V, et al. Definitive cetuximab-based (CRT-CX) vs. non-cetuximab based chemoradiation (CRT) in older patients with squamous cell carcinoma of the head and neck (HNSCC): Analysis of the SEER-Medicare linked database. J Clin Oncol. 2018;36(suppl; Abstract 6001).