New Trial Evaluates Neoadjuvant Therapies for Recurrent Head and Neck Cancer

A National Cancer Institute-funded phase 2 clinical trial (NCT07195734) is currently enrolling patients to evaluate survival outcomes for recurrent head and neck squamous cell carcinoma in patients who have previously undergone radiation therapy. This patient population accounts for up to 40% of cases and typically faces a poor prognosis, with surgery being the current standard of care.

The study compares the efficacy of surgery alone against neoadjuvant chemotherapy, with or without immunotherapy. Dr. Christina Henson, associate professor at the University of Oklahoma College of Medicine and radiation oncologist at the OU Health Stephenson Cancer Center, highlighted the existing challenges:

Surgical intervention for recurrence, despite being potentially curative, is often debilitating and has suboptimal survival rates. The trial seeks to determine if systemic therapy administered before surgery can extend disease-free and overall survival for these patients.

Trial Design

Eligible patients who are candidates for salvage surgery are randomly assigned to one of three arms:

• Arm 1: Neoadjuvant chemotherapy with carboplatin and paclitaxel.
• Arm 2: Neoadjuvant chemotherapy combined with the anti–PD-L1 immunotherapy cemiplimab (Libtayo). This arm is based on the high prevalence of PD-L1 expression in head and neck cancers, suggesting susceptibility to immune checkpoint inhibition.
• Arm 3: Surgery alone.

In Arm 1, patients receive intravenous paclitaxel and carboplatin on day 1 of each cycle, repeating every 21 days for 2 cycles. This is provided there is no disease progression or unacceptable toxicity.

In Arm 2, patients receive intravenous paclitaxel, carboplatin, and cemiplimab for 2 cycles under similar conditions.

In Arm 3, patients undergo salvage surgery.

Patients with high-risk features in any arm may receive daily radiation therapy for 5 treatments per week for 6 weeks, within 8 weeks of surgery.

Following the completion of study treatment, patients are followed up at 12 weeks or at the end of postoperative radiation. Subsequent follow-ups occur every 3 months for 2 years, every 6 months for years 3 and 4, and annually thereafter.

Objectives

The primary objective measure is the investigator-assessed event-free survival (EFS) of patients treated with chemotherapy or chemo-immunotherapy prior to salvage surgery, compared to those undergoing standard of care salvage surgery.

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

Dr. Mark Newpower, assistant professor in the OU College of Medicine and lead proton physicist at the Stephenson Cancer Center, commented on the focus on ensuring the technical precision:

Ensuring the technical precision and consistency of radiotherapy parameters across participating sites is vital for a multi-institutional study.

The protocol allows for adjuvant radiation therapy postoperatively for patients with high-risk pathological features.