In recent years, the fight against laryngeal cancer has made impressive strides, with cutting-edge treatment modalities altering how we treat this disease. Combining immunotherapy with conventional therapies like chemotherapy and radiation therapy is one such advancement. In the realm of oncology, concurrent pembrolizumab with chemoradiation has become a promising treatment option, especially for patients with locally advanced laryngeal cancer. Here is a detailed blog that explores the rationale behind the use of concurrent pembrolizumab with chemoradiation, its mechanism of action, and its potential impact on improving patient outcomes [1,2].
Understanding laryngeal cancer
The tissues of the larynx (also termed as voice box), are the main target of laryngeal cancer, sometimes referred to as larynx cancer. The larynx is a vital organ that protects the airways and is used for vocalization. Depending on where it manifests, the disease can be divided into three primary subtypes: supraglottic, glottic, and subglottic. Laryngeal cancer is often associated with risk factors like tobacco and alcohol consumption, whereas the human papillomavirus (HPV) has also been linked to some cases .
Standard of care for locally advanced laryngeal cancer
The currently used standard of care for locally advanced laryngeal cancer involves a combination of radiation therapy, chemotherapy, and surgery, depending on the stage, grade, and location of the tumor. Radiation therapy is employed to target and kill cancer cells using high-energy radiation, while chemotherapy, entailing systemic drugs, aims to eradicate cancer cells that may have spread beyond the primary site.
Surgery, in some cases, may involve the partial or total removal of the larynx, resulting in a permanent impairment in a patient's voice and quality of life. Laryngeal cancer management always involves balancing effective treatment with maintaining vocal function and quality of life [1–3].
The promise of immunotherapy in laryngeal cancer
In the field of oncology, immunotherapy, particularly PD-1/PD-L1 inhibitors like pembrolizumab have a revolutionary impact. Pembrolizumab (Keytruda) is an immune checkpoint inhibitor and belongs to the class of drugs known as monoclonal antibodies.
Pembrolizumab works by blocking the interaction between programmed cell death protein 1 (PD-1, expressed by immune cells) and its ligand (PD-L1) on cancer cells. This interaction suppresses the immune system's ability to recognize and attack cancer cells. This obstruction is virtually removed by pembrolizumab, enabling the immune system to identify and attack cancer cells. It has held great promise in the treatment of various cancers, offering patients new hope and better outcomes [1–3].
Combining pembrolizumab with chemoradiation
The use of immunotherapy along with conventional therapies is a novel approach that resolves numerous issues in the context of laryngeal cancer including:
Preservation of function: The preservation of vocal function and quality of life is the main advantage of immunotherapy for laryngeal cancer. Immunotherapy tries to eliminate cancer cells while maintaining the patient's capacity for effective communication, in contrast to surgical procedures that may cause long-term alterations to the patient's voice.
Improved response rates: Some laryngeal cancer patients may not respond well to conventional therapies or may experience a recurrence of cancer. Immunotherapy, when used in combination with conventional therapies like chemoradiation, can improve response rates and prolong disease-free survival [1–3].
The goal behind combining pembrolizumab and chemoradiation in the treatment of locally advanced laryngeal cancer is to increase the effectiveness of each treatment. Synergistic effects are produced by this combination therapy. When pembrolizumab is administered along with chemotherapy and radiation therapy,
The immune system becomes activated, which increases the body's ability to combat cancer.
It can lead to a more notable decrease in tumor size and possibly a complete response.
Early clinical trials and research have also revealed that giving pembrolizumab to patients with locally advanced laryngeal cancer concurrently with chemotherapy and radiation therapy may increase the survival rate and reduce the likelihood of disease recurrence [1–4].
Challenges and considerations
Research on the use of pembrolizumab in combination with chemoradiation for laryngeal cancer is still in its infancy. Although several encouraging clinical trials and studies offer helpful insights about its potential benefits, there are still certain challenges and considerations to take into account:
Patient Selection: Not all laryngeal cancer patients with localized advanced disease are likely to benefit from this treatment. Patient selection is essential to make sure that the potential benefits outweigh the risks and side effects.
Adverse events: Pembrolizumab can exhibit various immune-related adverse events, which need to be managed and monitored carefully. It is a crucial factor to take into account in future clinical trials investigating the optimal time to combine immunotherapy and chemoradiation [1–3].
The way to treat locally advanced laryngeal cancer has evolved from the regular use of total laryngectomy to the implementation of chemoradiation as a larynx‐preserving tactic. Despite its success in organ preservation, survival rate is minimal and treatment escalation is constrained by toxicity. Thus, the addition of immunotherapy in cancer treatment has offered new hope to patients with locally advanced laryngeal cancer. Concurrent pembrolizumab with chemoradiation is an innovative approach that prioritizes the preservation of voice function and quality of life in addition to improving treatment effectiveness. This combination therapy represents a substantial improvement in the treatment of laryngeal cancer as clinical studies and research continue to shed light on its possible benefits.
1. Khadela, A. et al. 'Immunomodulatory Therapy in Head and Neck Squamous Cell Carcinoma: Recent Advances and Clinical Prospects'. Technol Cancer Res Treat. (2023) 22, 15330338221150559. DOI: 10.1177/15330338221150559.
2. Cmelak, A.J. et al. 'Phase II Trial of Chemoradiation for Organ Preservation in Resectable Stage III or IV Squamous Cell Carcinomas of the Larynx or Oropharynx: Results of Eastern Cooperative Oncology Group Study E2399'. JCO. (2007) 25(25), 3971–3977. DOI: 10.1200/JCO.2007.10.8951.
3. Frankart, A.J. et al. 'A phase I/II trial of concurrent immunotherapy with chemoradiation in locally advanced larynx cancer'. Laryngoscope Investig Otolaryngol. (2022) 7(2), 437–443. DOI: 10.1002/lio2.780.
4. Jp, M. et al. 'Pembrolizumab given concomitantly with chemoradiation and as maintenance therapy for locally advanced head and neck squamous cell carcinoma: KEYNOTE-412'. Future oncology (London, England). (2020) 16(18). DOI: 10.2217/fon-2020-0184.