Head and Neck Cancer Treatment

He Head and neck cancer According to the report, it is the seventh most diagnosed cancer in our community, with an estimated 10,700 new cases and 3,660 deaths in Spain in 2024. Cancer figures in Spain 2024 and the latest data from the National Statistics Institute (INE). These tumors arise in an anatomically complex area, the local treatment of which for curative purposes is associated with serious physical consequences that are very stigmatizing and have a great impact in terms of quality of life and functionality of the triple sphere of phonation, swallowing and breathing. In recent years, the inclusion immunotherapy A therapeutic algorithm for patients with PD-L1-positive advanced head and neck cancer significantly increased survival in these patients.

In celebration of World Head and Neck Cancer Day, celebrated on July 27, the Spanish Society of Medical Oncology (SEOM) has highlighted the most important advances made in the treatment of this type of cancer.

Local and widespread disease

In maxillofacial and otolaryngological surgery, there has been an evolution from Hasted techniques to reconstructions and transplants, as well as the advent of robotic surgery, especially transoral surgery, which allows for resections that were previously technically unachievable. Conservative methods have been improved. such as supraglottic laryngectomy, which allows preserving phonation and avoiding a tracheostomy.

IN radiation therapyprogress has been made in techniques that can concentrate doses with less toxicity, such as intensity-modulated radiation therapy (IMRT) and radiosurgery, and methods for very precise dose delivery are being developed using technologies that allow very high-resolution planning. Similarly, deintensification techniques are being tested in HPV-associated tumors.

In most cases of stage I or II cancer surgery or radiation therapy is the treatment of choiceTreatment of locally advanced stage III or IV tumors (M0) is currently multimodal and includes surgery, radiation therapy and chemotherapy depending on the stage, location and clinical factors. In some cases, induction chemotherapy and subsequent radiation therapy allow the larynx to be preserved.

Treatment of patients with locally advanced head and neck cancer has evolved, and concurrent treatment radiation therapy and cisplatin This remains the standard today. In 2006, Bonner demonstrated that the efficacy of radiotherapy was increased when combined with cetuximab without increasing toxicity, making it now a good alternative to concomitant cisplatin except in patients with HPV-associated tumors. In 2022, the Treatment of Tumors in the Head and Neck (TTCC) Group published a phase III trial that attempted to demonstrate non-inferiority of cetuximab radiotherapy to cisplatin radiotherapy, but failed to achieve its non-inferiority goal.

Research with concomitant immunotherapy with radiotherapy were negative for the world population. We are currently waiting to learn the role of immunotherapy in the induction phase, whether or not associated with chemotherapy, and in the adjuvant phase after surgery or radiotherapy.

Recurrent or metastatic disease

In the area of ​​relapses it is possible salvage surgery or radiation therapy in combination with chemotherapy or cetuximabIn cases already irradiated, re-irradiation will be considered, but salvage is not always possible at this stage of the evolution. Patient selection is the key to achieving long-term survival; salvage treatment is indicated depending on the extent of the relapse, the time since previous radiotherapy, and the patient’s initial condition.

As for systemic treatment, The addition of cetuximab to standard chemotherapy was a significant advance for these patients.In recent years, the EXTREME (cisplatin, 5-fluorouracil, and cetuximab) and TPEX (cisplatin, docetaxel, and cetuximab) regimens have been promoted as treatment options for patients with advanced head and neck cancer. TPEX has established itself as a less toxic alternative to EXTREME, eliminating the need for a fluorouracil pump. ERBITAX (paclitaxel and cetuximab) is an effective therapeutic option for frail patients who are not candidates for cisplatin.

A major advance in the treatment of head and neck tumors has been the inclusion of immunotherapy in the therapeutic algorithm.. There was previously a therapeutic gap in cisplatin-refractory cases, particularly in patients refractory to EXTREME treatment, until 2016, when the FDA approved immunotherapy for these cases with two anti-PD-1 agents, the main benefit of which is long-term survival in responders. The FDA accelerated approval of nivolumab in April 2016 after presentation of data from the first pivotal phase III CHECKMATE 141 trial, in which nivolumab demonstrated an overall survival (OS) benefit versus investigator’s choice chemotherapy in patients who crossed over to platinum for localized disease. There was an improvement in OS (7.7 vs 3.3 months), but most striking was that more than 10% of patients in the nivolumab group were alive at 3 years.

On September 1, 2016, the FDA granted accelerated approval to pembrolizumab based on data from the non-randomized Phase Ib KEYNOTE-012 trial. Most patients in the study had previously received at least two different cycles of treatment. A median overall survival of 8 months was achieved, with 38% of patients still alive one year after starting treatment. A Phase II trial (KEYNOTE-055) subsequently confirmed these data in a 2017 publication in Journal of Clinical Oncology.

In 2018, the results of the KEYNOTE-048 study were published, demonstrating the superiority of pembrolizumab as monotherapy and pembrolizumab in combination with cisplatin-based chemotherapy in first-line patients with recurrent and/or metastatic disease with platinum-sensitive disease and a positive PDL1 result. Since 2021, it has been included in the standard treatment of this group of patients with positive PDL1, and this is reflected in the SEOM Guidelines for the treatment of these tumors. But perhaps the most impressive aspect is the reduction in the risk of mortality that is observed with the introduction of these drugs. In an updated version of the study published in 2023 with a 4-year follow-up, Treatment with pembrolizumab has been shown to reduce the risk of death compared with standard chemotherapy by 26-39%. according to PD-L1 expression and the combination of chemotherapy and pembrolizumab – 38%.