Advancements in Head and Neck Cancer Treatment: A New Era of Hope

Each year, approximately 16,000 new cases of malignant head and neck tumors are diagnosed in France, with 10% being rare cancers not classified as conventional squamous cell carcinomas [1]. While historically challenging due to late-stage diagnoses and high recurrence rates, significant progress is being made in treatment approaches, offering renewed hope for patients. Standard first-line treatments remain radiotherapy, radiochemotherapy, or surgery followed by radiotherapy or radiochemotherapy. However, immunotherapy and novel targeted therapies are rapidly changing the landscape of care.

Immunotherapy: A Paradigm Shift

Immunotherapy, particularly with antibodies targeting the PD-1 protein (programmed cell death protein 1), like pembrolizumab (Keytruda) and nivolumab (Opdivo), has shown promise in metastatic or recurrent cases. Recent phase III trials are now demonstrating benefits when administered perioperatively – before and after surgery – for patients with resectable, locally advanced carcinoma.

The Keynote-689 study utilized pembrolizumab neoadjuvantly and adjuvantly, alongside standard treatment [2]. The Nivopostop trial tested nivolumab in addition to traditional post-surgical treatments. Both studies showed a clear improvement in event-free survival at two years, meaning a reduced risk of metastasis or locoregional relapse. Pembrolizumab has already received validation from the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA) for this perioperative use.

Bispecific Antibodies: Targeting Cancer with Precision

Researchers are similarly exploring bispecific antibodies, a new class of drugs targeting non-operable metastatic or recurrent tumors. These antibodies act on the epidermal growth factor receptor (EGFR), which is frequently overexpressed on tumor cells, and a second target that varies depending on the specific antibody.

• Petosemtamab: This antibody binds to both EGFR and the LGR5 receptor, crucial for cancer cell growth and survival. In a phase II study, petosemtamab combined with pembrolizumab achieved a 60% response rate, compared to 20% with pembrolizumab alone. Phase III trial results are expected in 2026. It has already received “fast track” status from the FDA.
• Amivantamab: Targeting EGFR and MET, this antibody aims to overcome resistance to EGFR inhibition. Combined with immunotherapy and chemotherapy, it demonstrated a response rate of around 45%. Its subcutaneous injectable form offers faster administration and may reduce the risk of cytokine release syndrome, a serious immune-related complication. Phase III trials (OrigAMI-5) are ongoing.
• Ficerafusp alfa: This treatment interferes with EGFR and neutralizes TGF-β, a cytokine that suppresses the immune response within the tumor microenvironment. Early trials showed response rates of approximately 54% when combined with pembrolizumab. Phase II and III results are anticipated in 2028.

Vaccine Therapy and Emerging Approaches

The TG4050 therapeutic vaccine, developed by Transgene, is showing promising preliminary results. Personalized to each patient based on a biopsy of their tumor, the vaccine identifies 30 specific targets (neoantigens). A randomized phase I study showed no recurrence at 54 months of follow-up in the vaccinated arm.

Other areas of development include antibody-drug conjugates (ADCs), which deliver cytotoxic agents directly into cancer cells. An ADC targeting nectin-4, combined with chemotherapy, showed response rates of 39%, reaching 82% in HPV-induced cancers and is entering phase II trials.

The Importance of Prevention and Early Detection

While tobacco and alcohol remain significant risk factors, HPV infections are increasingly linked to head and neck cancers, particularly in young, non-smoking individuals in the oropharynx. Anti-HPV vaccination is an effective preventative measure. Early diagnosis is also crucial; any persistent symptoms lasting longer than three weeks should be evaluated by a healthcare professional. The ENT cancer awareness campaign Robin will be held from March 30 to April 4 [2].

Modernizing Surgical Techniques and Radiotherapy

Surgical techniques are evolving towards more minimally invasive endoscopic procedures performed through the mouth. Reconstruction methods are also innovating, such as the Bioface project, utilizing biomaterials to replace tissue flaps. Radiotherapy advancements include Flash technology, delivering high doses in milliseconds, and nanoparticle injection to enhance targeted radiation effects.

These advancements collectively aim to improve patient care, reduce adverse effects, and enhance the quality of life for those affected by head and neck cancers.