Treatment with the immuno-therapeutic nivolumab (Opdivo) improved survival for patients with recurrent or metastatic head and neck squamous cell carcinoma that progressed after platinum-based chemotherapy compared with single-agent chemotherapy of the investigator’s choice, according to results from the CheckMate-141 phase III clinical trial presented here at the AACR Annual Meeting 2016.

“Recurrent or metastatic head and neck squamous cell carcinoma that is not responsive to platinum-based chemotherapy progresses very rapidly, and patients have a very poor prognosis,” said Maura L. Gillison, MD, PhD, a professor in the Department of Internal Medicine at The Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute.

“Treatment usually involves single-agent chemotherapy. However, no therapy has been shown to improve survival for this patient population. New treatment options are desperately needed. This study is the first randomised clinical trial to clearly demonstrate improved overall survival for patients with platinum-refractory recurrent or metastatic head and neck squamous cell carcinoma,” continued Gillison. “We hope that the results will establish nivolumab as a new standard of care option for this patient population and thereby fulfil a huge unmet need.”

CheckMate-141 was a randomised, phase III clinical trial designed to determine whether the PD- 1 inhibitor nivolumab could extend overall survival for patients with platinum-refractory recurrent or metastatic head and neck squamous cell carcinoma compared with treatment of the investigator’s choice, which was any of the commonly used therapeutics docetaxel, methotrexate, or cetuximab.

Of the 361 patients enrolled in the clinical trial, 240 were randomly assigned to nivolumab and 121 to single-agent chemotherapy of investigator’s choice.

At the interim analysis, which was conducted after 218 events, patients assigned to nivolumab were found to have a 30 percent reduction in risk of death compared with those assigned therapy of investigator’s choice.

Median overall survival was 7.5 months for those assigned nivolumab versus 5.1 months for those assigned therapy of investigator’s choice.

At 12 months, 36 percent of the patients treated with nivolumab were alive compared with 17 percent of those assigned therapy of investigator’s choice.

For patients assigned nivolumab, the overall response rate (ORR, which is the proportion of patients who had a partial or complete response, as defined by RECIST 1.1 criteria) was 11.7 percent, with six complete responses and 22 partial responses, and for those assigned therapy of investigator’s choice, the ORR was 7.4 percent, with one complete response and eight partial responses.

Because certain types of head and neck squamous cell carcinoma, particularly those arising in the oropharynx (back of the throat, including the base of the tongue and tonsils), have been linked with human papillomavirus (HPV) infection, the investigators also evaluated the data based on the HPV status of the patients’ tumours.

The effect of nivolumab on overall survival was seen for both patients with HPV-positive disease and those with HPV-negative disease.

Among patients with HPV-positive disease, median overall survival was 9.1 months for those assigned nivolumab versus 4.4 months for those assigned therapy of investigator’s choice, and among patients with HPV-negative disease, median overall survival was 7.5 months for those assigned nivolumab versus 5.8 months for those assigned therapy of investigator’s choice.

A survival benefit in patients treated with nivolumab was observed for the overall study population.

Exploratory analysis suggested that the benefit was greater for patients treated with nivolumab whose tumours had PD-L1 expression (of 1 percent or greater) or were HPV-positive.

“Overall, our data are extremely exciting. This clinical trial has established head and neck squamous cell carcinoma as responsive to immunotherapy. We are hopeful that this represents the tip of the iceberg with regard to future benefit of immunotherapy for patients with head and neck squamous cell carcinoma,” added Gillison.

Source: AACR