A new clinical trial exploring a combination of chemotherapy and immunotherapy shows promising results for patients with advanced human papillomavirus (HPV)-negative head and neck squamous cell carcinoma (HNSCC). The Phase II, nonrandomized study, led by researchers at the University of Chicago (UChicago) Medicine Comprehensive Cancer Center, evaluated the impact of a novel treatment regimen that combines nivolumab, an immunotherapy drug, with chemotherapy followed by response-adaptive chemo-radiation therapy.
The trial results, published in JAMA Oncology, suggest that this combination treatment could offer a significant step forward in treating HPV-negative HNSCC, particularly given the difficulty of managing the disease with current therapies.
“More than half of study participants had 50% or more of their tumors shrink after receiving the immunotherapy drug nivolumab with chemotherapy, followed by response-adaptive chemo-radiation therapy,” said first author of the study Ari Rosenberg, MD, an assistant professor of medicine at UChicago Medicine.
HPV-negative HNSCC is a particularly challenging cancer to treat, especially at advanced stages. Often diagnosed in older patients with a history of smoking and alcohol use, this form of cancer tends to have poor survival rates. The lack of early symptoms makes the cancer difficult to detect in its initial stages, leading to diagnoses at later, more advanced stages. Once the cancer reaches stage 3 or 4, treatment options are limited. Those therapies that are available are often aggressive and can significantly impact a patient’s speech and ability to swallow.
The new combination approach aims to address two major unmet needs: improving survival rates and reducing long-term toxic effects associated with treatment.
The clinical trial tested the combination of three cycles of neoadjuvant chemotherapy with nivolumab, followed by a response-adaptive de-escalation approach to chemo-radiation therapy. Of the 36 participants, 53% showed a deep response, defined as a 50% or greater reduction in tumor size after the neoadjuvant treatment. Researchers also observed that patients with higher levels of programmed death-ligand 1 (PD-L1), a protein often found in tumors, had more favorable treatment responses.
“This result exceeded our expectations over our historical data with chemotherapy alone,” Rosenberg said. “Deeper responses were observed in patients with higher expression of PD-L1, suggesting that PD-L1 expression could serve as a potential biomarker to predict treatment response.”
The study also measured survival outcomes, treatment toxicities, and overall quality of life. Two-year progression-free survival was 66%, and overall survival was 73%. The findings showed that patients who responded well to the neoadjuvant treatment and received de-escalated radiation therapy experienced fewer acute toxic effects, such as mucositis, radiation dermatitis, and dry mouth, compared to those who received the standard radiation regimen.
“This is the first study, to our knowledge, that evaluates neoadjuvant chemo-immunotherapy followed by response-adaptive de-escalation treatment in non-surgical HPV-negative HNSCC patients,” said Rosenberg. “These promising results pave the way for new treatment paradigms that not only improve survival but also enhance the quality of life for these patients.”
Based on this trial, the researchers will continue to explore the role of biomarkers like PD-L1 in predicting patient responses and will continue to refine the combination of therapies to further improve patient outcomes. As the researchers continue to follow this cohort of patients, they will gather more data on long-term survival and side effects, potentially setting the stage for a broader application of this treatment approach in clinical practice.
