Adjuvant Nivolumab Plus Chemoradiotherapy Meets DFS End Point in Locally Advanced HNSCC

The addition of nivolumab (Opdivo) to standard-of-care (SOC) adjuvant therapy comprising cisplatin and radiotherapy led to a statistically significant and clinically meaningful improvement in disease-free survival (DFS) compared with adjuvant chemoradiotherapy alone in patients with resected, locally advanced head and neck squamous cell carcinoma (HNSCC), meeting the primary end point the phase 3 NIVOPOSTOP trial (NCT03576417).1

An announcement from GORTEC (Head and Neck Radiation Oncology Group) also noted that although overall survival (OS) data were not mature at the time of this analysis, a positive trend was observed favoring the nivolumab arm. OS will be fully evaluated at the final analysis after the pre-specified number of deaths occur during the study.

Safety data showed nivolumab’s profile was consistent with findings from prior studies, and compliance rates for the SOC therapies were similar between the 2 arms.

“This is the first time in decades where a therapy demonstrated superiority over SOC cisplatin-radiotherapy in high-risk patients with locally advanced HNSCC," Jean Bourhis, MD, PhD, principal investigator of NIVOPOSTOP and medical director of GORTEC, stated in a news release.

NIVOPOSTOP was a randomized, controlled, open-label trial investigating the addition of nivolumab to SOC radiotherapy and cisplatin compared with SOC radiotherapy and cisplatin alone. Investigators enrolled 680 patients between 18 and 75 years of age with histologically confirmed, stage III or IV, resected, locally advanced HNSCC who had high-risk factors for relapse, including nodal extracapsular extension, multiple nodal involvement, multiple perineural invasions, or positive surgical margins.1,2 Completion of macroscopic resection and recovery from surgery to allow for the administration of chemoradiotherapy was required, and patients needed to be free from disease.2 Those with oropharyngeal tumors needed to have a known p16 status per immunohistochemistry. Patients with stage II, p16-positive oropharyngeal cancer were allowed to enroll if they had pT3N1 or pT4N1 disease, plus a tobacco consumption history of at least 20 packs per year.

Patients were excluded if they had nasopharyngeal, paranasal sinuses, nasal cavity, or thyroid cancers; had squamous cell carcinoma involving cervical neck nodes with an unknown primary site; had metastatic disease; underwent incomplete macroscopic resection; or had central nervous system disease. Other than surgery, no prior treatment for the current malignancy was permitted, including prior TKIs, monoclonal antibodies, induction chemotherapy, radiotherapy, or any investigational agent.

Patients were randomly assigned to receive either SOC radiotherapy at 66 Gy over 6.5 weeks plus cisplatin at 100 mg/m² every 3 weeks for 3 cycles; or the same SOC chemoradiotherapy regimen in combination with nivolumab.1,2 In the experimental arm, patients received a 240-mg dose of nivolumab alone 3 weeks prior to the start of SOC chemoradiotherapy, which was given concurrently with nivolumab at 360 mg once every 3 weeks.2 Following the completion of SOC radiotherapy in the experimental arm, nivolumab was continued as maintenance at 480 mg once every 4 weeks for up to 6 cycles.1,2

Along with the primary end point of DFS, secondary end points included OS and the rates of acute and late toxicities.2

"These clinically meaningful findings have the potential to be practice-changing for high-risk LA-SCCHN patients receiving adjuvant therapy," Yoann Pointreau, MD, and Yun Gan Tao, MD, added in a news release.1 Pointreau is the current president of GORTEC, and Tao is the president-elect.

References

1. GORTEC announces new trial success for head and neck cancer treatment. News release. GORTEC. January 7, 2025. Accessed January 9, 2025. https://www.prnewswire.com/news-releases/gortec-announces-new-trial-success-for-head-and-neck-cancer-treatment-302344111.html
2. A trial evaluating the addition of nivolumab to cisplatin-RT for treatment of cancers of the head and neck (NIVOPOSTOP). Clinicaltrials.gov. Updated July 5, 2024. Accessed January 9, 2025. https://clinicaltrials.gov/study/NCT03576417