Neoadjuvant Systemic Therapy Explored in Head and Neck Cancer Trial

A National Cancer Institute-funded phase 2 clinical trial (NCT07195734) is now enrolling patients to evaluate survival outcomes for recurrent head and neck squamous cell carcinoma following prior radiation therapy. This patient population, representing up to 40% of cases, faces a poor prognosis with surgery as the current standard of care. The trial compares the efficacy of surgery alone vs neoadjuvant chemotherapy with or without immunotherapy.

“Surgical intervention for recurrence, while potentially curative, is often profoundly debilitating and is still associated with suboptimal survival. This trial seeks to determine if systemic therapy administered prior to surgery can extend disease-free and overall survival for these patients,” Christina Henson, MD, associate professor at the University of Oklahoma College of Medicine and radiation oncologist at the OU Health Stephenson Cancer Center, said in a release. Henson serves as the national radiation oncology chair for the study and emphasized the critical need for improved therapeutic strategies.

Trial Design

Eligible patients who are candidates for salvage surgery will be randomly assigned to 1 of 3 arms: neoadjuvant chemotherapy with carboplatin and paclitaxel (arm 1), neoadjuvant chemotherapy combined with the anti–PD-L1 immunotherapy cemiplimab (Libtayo; arm 2), or surgery (arm 3). The cemiplimab arm is predicated on the high prevalence of PD-L1 expression in head and neck cancers, which indicates a potential susceptibility to immune checkpoint inhibition.

In arm 1, patients will receive paclitaxel and carboplatin intravenously (IV) on day 1 of each cycle and cycles repeat every 21 days for 2 cycles in the absence of disease progression or unacceptable toxicity. In arm 2, patients receive paclitaxel, carboplatin, and cemiplimab intravenously for 2 cycles without progression or toxicity. In arm 3, patients undergo SS. Within 8 weeks of surgery, patients with high-risk features also undergo radiation therapy daily for 5 treatments per week for 6 weeks.

After completion of study treatment, patients are followed up at 12 weeks or at the end of post operative radiation, then every 3 months for 2 years, every 6 months for years 3 and 4 and annually thereafter.

Objectives

The primary objective measure is investigator-assessed event-free survival (EFS) of patients treated with chemotherapy (carboplatin plus paclitaxel) or chemo-immunotherapy (carboplatin plus paclitaxel and cemiplimab) prior to salvage surgery (SS) versus patients undergoing standard of care SS.

Secondary objectives are disease-free survival (DFS), overall survival (OS), and distant metastasis. Exploratory outcomes include event-free survival, DFS, and OS.

“Our contribution has focused on ensuring the technical precision and consistency of radiotherapy parameters across participating sites, which is vital for a multi-institutional study of this nature,” Mark Newpower, PhD, assistant professor in the OU College of Medicine and lead proton physicist at the Stephenson Cancer Center, serves as the national medical physics chair, said. Per protocol, patients with high-risk pathological features may receive adjuvant radiation therapy postoperatively.