The Phase 3 NIVOPOSTOP GORTEC 2018-01 trial has revealed that adding nivolumab (Opdivo) to standard-of-care (SOC) cisplatin-radiotherapy significantly improves disease-free survival (DFS) in patients with resected, locally advanced squamous cell carcinoma of the head and neck (LA-SCCHN) at high risk of relapse. This randomized, controlled, open-label study, could redefine the post-operative treatment landscape for this patient population.
The trial (NCT03576417) compared the addition of nivolumab to SOC radiotherapy and cisplatin against SOC radiotherapy and cisplatin alone. The primary endpoint was DFS, with overall survival (OS) as a key secondary endpoint. The study enrolled 680 patients who were randomized after surgery to receive either SOC 66 Gy radiotherapy and cisplatin (100 mg/m2 Q3W for three cycles) or nivolumab 240 mg, followed by SOC cisplatin-radiotherapy with nivolumab 360 mg Q3W every 3 weeks during cisplatin-radiotherapy and followed by 6 cycles of nivolumab 480 mg every 4 weeks.
Key Findings
According to Prof. Jean Bourhis, Principal Investigator of the study and Medical Director of GORTEC, this is "the first time in decades where a therapy demonstrated superiority over standard of care cisplatin-radiotherapy in high-risk patients with LA-SCCHN". The study met its primary endpoint, demonstrating a statistically significant and clinically meaningful improvement in DFS for patients receiving nivolumab.
A trend toward improvement in OS was also observed for nivolumab, although the final analysis will be conducted once the pre-specified number of deaths has been reached. The safety profile of nivolumab was consistent with that reported in previous studies, and compliance to SOC treatments was similar between the two arms of the study.
Patient Population and Treatment
The trial included patients with resected LA-SCCHN who were at high risk of relapse, defined by criteria such as nodal extra capsular extension, multiple nodal involvement, multiple peri-neural invasion, and/or positive tumor margins after surgery. Patients received either SOC radiotherapy and cisplatin or nivolumab in combination with SOC cisplatin-radiotherapy.
Implications for Clinical Practice
The results suggest that adjuvant nivolumab has the potential to be practice-changing for high-risk LA-SCCHN patients receiving adjuvant therapy. Drs. Yoann Pointreau, President of GORTEC, and Yun Gan Tao, President-Elect of GORTEC, added that these findings have the potential to significantly impact the treatment of these patients.
About Head and Neck Cancer
Head and neck cancer, encompassing malignancies of the oral cavity, nasopharynx, oropharynx, hypopharynx, and larynx, is the sixth most common cancer worldwide. In 2022, there were 891,453 new cases and 458,107 deaths globally. Approximately 60% of patients are diagnosed with locally advanced (LA) disease. Current treatment guidelines recommend surgical resection followed by radiotherapy or cisplatin-radiotherapy for high-risk cases. However, a significant proportion of LA-SCCHN patients experience locoregional recurrence or distant metastases within two years of completing treatment, highlighting the need for more effective adjuvant therapies.
