Nivolumab/Cisplatin/Radiotherapy Improves DFS in Locally Advanced SCCHN

The phase 3 NIVOPOSTOP GORTEC 2018-01 trial shows that nivolumab added to radiotherapy and cisplatin had improved efficacy over SOC treatments in SCCHN.

Nivolumab (Opdivo), an anti–PD-1 therapy, has met the primary end point of disease-free survival (DFS) across all comers in the phase 3 NIVOPOSTOP GORTEC 2018-01 trial (NCT03576417) as a post-operative treatment component for patients with resected locally advanced squamous cell carcinoma of head and neck (SCCHN) who have a high risk of relapse, a press release from the Head and Neck Radiation Oncology Group (Groupe Oncologie Radiotherapie Tete et Cou; GORTEC) stated.¹

The NIVOPOSTOP trial investigated the efficacy and safety of adding nivolumab to standard-of-care (SOC) radiotherapy and cisplatin compared with SOC radiotherapy and cisplatin alone in patients with locally advanced SCCHN.

Jean Bourhis, MD, PhD, professor and chief of radiation oncology at the Lausanne University Hospital in Lausanne, Switzerland; medical director of GORTEC; and principal investigator of the study, said, “This is the first time in decades where a therapy demonstrated superiority over [SOC] cisplatin-radiotherapy in high-risk patients with [locally advanced] SCCHN.”¹

There was a clinically meaningful and statistically significant improvement in DFS for patients who received nivolumab, which was determined based on a pre-determined number of DFS events. Additionally, with similar compliance to SOC treatments across the 2 arms of the study, the safety profile of nivolumab remained comparable with those reported in prior studies.

Nivolumab also produced a trend towards improved overall survival (OS), which will be evaluated at the final analysis when the pre-specified number of deaths has been met.

The trial’s primary end point was DFS, defined as the time between the date of randomization and the date of first loco-regional or distant recurrence or death of any cause.² Secondary end points included OS; acute toxicity, defined as the maximal grade of each toxicity observed during radiotherapy plus concomitant treatment according to NCI CTCAE v5.0 criteria; and late toxicity.

NIVOSTOP GORTEC 2018-01 is an open-label, randomized, controlled phase 3 trial that enrolled a total of 680 patients. All patients were randomly assigned, in a 1:1 ratio, following surgery to receive either 66 Gy of SOC radiotherapy and 100 mg/m² of cisplatin once every 3 weeks for 3 cycles or 240 mg of nivolumab every 3 weeks plus SOC cisplatin-radiotherapy with 360 mg of nivolumab on days 1, 22, and 43 of cisplatin-radiotherapy followed by a maintenance phase of 480 mg of nivolumab. Stratification was based on P16 status (p16-positive oropharyngeal cancer vs no oropharyngeal cancer or p16-negative oropharyngeal cancer).

Patient eligibility criteria included an age between 18 and 75 years; an ECOG performance status of 0 or 1; histologically proven SCCHN from the oral cavity, oropharynx, hypopharynx, or larynx; histopathological classification of pStage III or IV per the 8th edition of the American Joint Committee on Cancer; a high risk of relapse; complete macroscopic resection; and being free of disease.

Patients were excluded from participation if they had nasopharyngeal, paranasal sinuses, nasal cavity tumors, or thyroid cancers. Other exclusion criteria included metastatic disease, active central nervous system disease, squamous cell carcinoma involving cervical neck nodes with unknown primary site, interstitial lung disease, and any prior treatment for the current head and neck cancer other than primary surgery. Having severe acute or chronic medical conditions including colitis, pneumonitis, pulmonary fibrosis, laboratory abnormalities, or other significant disease was also grounds for exclusion.

“These clinically meaningful findings have the potential to be practice-changing for [patients with] high-risk [locally advanced] SCCHN receiving adjuvant therapy,” Yoann Pointreau, MD, president of GORTEC, and Yungan Tao, MD, president-elect of GORTEC, added in the release.¹

References

1. GORTEC announces new trial success for head and neck cancer treatment. News release. GORTEC. January 7, 2025. Accessed January 8, 2025. https://tinyurl.com/5n8wuez7
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 8, 2025. https://tinyurl.com/hxvtju8p