Head and neck cancers rank as the seventh most common type of cancer globally, significantly impacting smokers, drinkers, and individuals with HPV infections. Cisplatin, a standard chemotherapy drug, coupled with radiation therapy, remains the gold standard for treating these cancers. However, over 30% of patients, particularly older adults and those with pre-existing kidney disease or hearing loss, cannot tolerate cisplatin due to severe side effects.
The Search for Alternatives to Cisplatin
For patients who cannot tolerate cisplatin, the monoclonal antibody cetuximab is often used as an alternative, despite being less effective. The absence of a consensus on the standard of care for this subset of patients has led researchers to explore other options. Durvalumab, an immune checkpoint inhibitor, has shown promise in treating various cancers and was proposed as a potentially safer, more effective substitute for cetuximab. Dr. Loren Mell, a professor at the University of California San Diego School of Medicine, spearheaded a clinical trial to compare the effectiveness of durvalumab and cetuximab, each combined with radiation therapy. The trial involved 186 patients with advanced squamous cell carcinoma of the head or neck who were ineligible for cisplatin.
The trial aimed to provide a thorough evaluation of these two therapies, examining the potential benefits and drawbacks of each drug when used in conjunction with radiation. By investigating these alternative treatment options, researchers sought to determine the most effective strategy for this specific patient population, hoping to establish a new standard of care that could offer patients a better chance at overcoming cancer while minimizing adverse effects.
Clinical Trial Findings
Published in The Lancet Oncology, the study found, contrary to expectations, that cetuximab performed better than durvalumab in terms of effectiveness. Both drugs demonstrated comparable rates of adverse events, leading researchers to halt the study prematurely. The two-year survival rate free of disease was approximately 64% for cetuximab-treated patients compared to 51% for those receiving durvalumab, indicating no benefit from durvalumab over cetuximab. Dr. Mell emphasized that the promising expectations for durvalumab were not realized, as it turned out to be potentially less effective than cetuximab. Monoclonal antibodies like cetuximab function by binding to proteins on the surface of cancer cells, halting their growth and proliferation. In contrast, durvalumab blocks a protein on cancer cells called PDL1, enabling the immune system’s T cells to target and attack the cancer cells directly.
This difference in mechanism highlights the varied approaches these drugs take in combating cancer, with cetuximab directly interfering with cancer cell growth while durvalumab aims to enhance the body’s immune response. Despite the initial hopes for durvalumab’s effectiveness, the findings demonstrated that cetuximab remains the more reliable option for those who cannot tolerate cisplatin, prompting a reevaluation of treatment strategies for this particular group of patients.
Implications for Treatment Paradigms
The study significantly impacts the treatment paradigm for head and neck cancers as the first of its kind conducted in North America for patients ineligible for cisplatin. This groundbreaking trial demonstrated a higher success rate for cetuximab than any previous study in patients unable to undergo cisplatin treatment. Consequently, cetuximab is likely to become the new standard of care for these individuals. Additionally, the study revealed that cetuximab’s efficacy was consistent regardless of a patient’s HPV status. Mell highlighted that the study reinforces the notion that radiation therapy combined with cetuximab is a viable alternative for patients who cannot receive the standard cisplatin treatment.
Historically, this group has been underserved, and the trial aimed to establish a solid evidence base for this unique population, predominantly consisting of older adults and those with other health issues that have often led to their exclusion from clinical trials. As radiation therapy with cetuximab emerges as a new standard treatment, the study’s findings pave the way for improved management of head and neck cancer in patients previously unable to benefit from the gold standard treatment of cisplatin.
Future Research Directions
Head and neck cancers are the seventh most common type of cancer worldwide, greatly affecting smokers, drinkers, and those infected with the human papillomavirus (HPV). Cisplatin, a standard chemotherapy drug, in combination with radiation therapy, continues to be the primary treatment for these cancers. This combination is widely regarded as the gold standard due to its effectiveness. Nevertheless, there is a significant drawback: more than 30% of patients are unable to tolerate cisplatin. This is especially true for older adults and individuals with pre-existing conditions, such as kidney disease or hearing impairment. The severe side effects of cisplatin, which can include damage to the kidneys and hearing loss, limit its use. This presents a substantial challenge in treating head and neck cancers effectively in this subgroup of patients. As the medical community continues to search for alternative treatments that are both effective and less harsh, the need for safe and efficient therapies remains critical for improving patient outcomes and quality of life.
