Phase III data for nivolumab in head and neck cancer show biggest increase in survival for 20 years

Bristol-Myers Squibb has announced results from the pivotal CheckMate -141 Phase III clinical trial which showed that treatment with nivolumab, which is investigational in head and neck cancer, achieved superior survival rates compared with current standard chemotherapies. In patients with recurrent or metastatic platinum-refractory squamous cell carcinoma of the head and neck, more than double the number of patients treated with nivolumab were still alive at one year vs. the comparator arm (36%, [95% CI: 28.5-43.4] vs. 16.6%, [95% CI: 8.6-26.8]).2 The study also demonstrated a 30% reduction in the risk of death in favour of nivolumab (median overall survival (OS) 7.5 months (95% CI: 5.5-9.1) for nivolumab vs. 5.1 months (95% CI: 4.0-6.0) for the comparator arm (HR=0.70 [95% CI: 0.51, 0.96] p=0.0101).¹ Four centres in the UK took part in this study and the results were presented in a late-breaking presentation at The American Association for Cancer Research (AACR) Annual Meeting 2016 in New Orleans. Head and neck cancer is the seventh most common cancer in the UK and almost a third of newly diagnosed patients died from the disease in 2012.3 With incidence rates having risen by over 30% in the last 15 years in Europe, this group of cancers represents a growing health burden.²

"We don't have effective treatments for advanced head and neck cancers - these cancers are notoriously difficult to treat. So it's exciting that this phase III trial has been the first to show a significant survival benefit with an immunotherapy," said UK principal investigator Professor Kevin Harrington, Professor of Biological Cancer Therapies at The Institute of Cancer Research, London, and consultant oncologist at The Royal Marsden NHS Foundation Trust. "Nivolumab was not only more effective than chemotherapy for patients with head and neck cancer but also had fewer side-effects, and has the potential to significantly extend life and increase quality of life."

Due to the survival benefit observed with nivolumab, the Checkmate-141 trial was stopped early based on a recommendation from an independent monitoring committee. All remaining patients on the comparator chemotherapy arms in the trial were then given the option of receiving treatment with nivolumab. Nivolumab is the first in a new class of medicines, called PD-1 immune checkpoint inhibitors. This type of approach has an innovative mode of action that works by harnessing the ability of the immune system to fight head and neck cancer.³ This means it works quite differently and offers a different side effect profile that is considered manageable compared with some traditional chemotherapies.^4,5

In the CheckMate -141 study, the safety profile of nivolumab was consistent with prior studies and no new safety signals were identified. Grade ≥3 treatment-related adverse events (side effects) were seen in 13.1% of patients receiving nivolumab vs. 35.1% of patients on standard chemotherapies.2 The most frequently reported treatment related adverse events of any grade occurred in 58.9% of patients on nivolumab vs. 77.5% of patients on the investigators choice of standard chemotherapy; two treatment-related deaths were reported as related to nivolumab (pneumonitis and hypercalcemia), and one Grade 5 event of lung infection on the investigator's choice arm.¹

Head and neck cancer is becoming an increasingly prevalent disease in the UK and around 11,300 new cases each year are diagnosed^6-10 - an average of 31 every day.3 It is also a highly complex and debilitating disease to treat.² Initial treatment includes surgery and/or radiotherapy² followed by chemotherapy/radiotherapy and latterly chemotherapy alone. However, many patients will progress and are no longer able to tolerate these options due to age or poor health status and for those whose cancer has spread (metastasised), treatment and management is focused on keeping the cancer at bay and support through palliative care.²

Jean Viallet, M.D., Global Clinical Research Lead, Oncology, Bristol-Myers Squibb, commented, "We are excited to share, for the first time, data from the CheckMate -141 trial with the oncology community at the 2016 AACR Annual Meeting. We are encouraged by the overall survival results seen with this investigational use of nivolumab versus three standards of care for patients with recurrent or metastatic squamous cell carcinoma of the head and neck, who often face poor survival rates. These findings are supportive of our Immuno-Oncology research goal to study potential treatment options for their ability to help patients with difficult-to-treat cancers achieve long-term survival."

About the CheckMate -141 study

CheckMate -141 is a Phase III, randomised study which evaluated nivolumab as a single agent (n=240) versus investigators choice of therapy, methotrexate, docetaxel, or cetuximab (n=121) in patients with recurrent or metastatic platinum-refractory squamous cell carcinoma of the head and neck.2 The primary endpoint of the study was overall survival. In the UK, the CheckMate -141 study involved four trial sites - The Royal Marsden NHS Foundation Trust, The Christie NHS Foundation Trust, The Clatterbridge Cancer Centre and University Hospital Southampton.

About nivolumab

Under the brand name Opdivo, nivolumab is licensed in Europe for adult patients with advanced (unresectable or metastatic) melanoma, for the treatment of locally advanced or metastatic non-small cell lung cancer (NSCLC) after prior chemotherapy in adult patients, and for the treatment of advanced renal cell carcinoma after prior therapy in adults.³

Bristol-Myers Squibb has a broad, global development programme to study nivolumab in multiple tumour types consisting of more than 50 trials - as monotherapy or in combination with other therapies - in which more than 8,000 patients have been enrolled worldwide.